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Results for “Surrogate variables analysis”

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At least 73 records · Page 4Linked to original sources

PubMed2001

Hemodynamics as surrogate end points for survival in advanced heart failure: an analysis from FIRST.

BACKGROUND: Hemodynamics often are used as surrogate end points in phase II trials of acute heart failure (HF). We reviewed the Flolan International Randomized Survival Trial (FIRST) database to identify the hemodynamic variables that best predict survival in patients with advanced HF receiving epoprostenol therapy and to determine whether hemodynamics could predict the overall effect of a drug. METHODS: The trial enrolled 471 patients with class IIIb/IV HF and ejection fraction or=3 months, all of whom underwent screening pulmonary artery catheter insertion. Patients were randomly assigned to receive either epoprostenol (n = 201) or placebo (n = 235); epoprostenol therapy was guided by pulmonary artery catheter measures, and standard treatment was guided by clinical findings. Multivariable modeling was used to identify and quantify the demographic, clinical, and hemodynamic variables most associated with 1-year survival. RESULTS: In multivariable modeling, HF class, decreased pulmonary capillary wedge pressure (PCWP), and age best predicted 1-year survival. After adjustment for age and HF class, decreased PCWP still significantly predicted survival (hazard ratio, 0.96 for every 1-mm Hg decrease; 95% confidence interval, 0.94 to 0.99; P = .003). Survival was significantly higher with decreases in PCWP >or=9 versus <9 mm Hg, even after adjustment for age and HF class. Survival of patients in the PCWP >or=9 group was comparable with, and that of the PCWP <9 group was significantly higher than, survival of patients in the control group (hazard ratio, 1.44; 95% confidence interval, 1.05 to 1.99; P = .024). CONCLUSIONS: The reduction in PCWP was the hemodynamic measure most predictive of survival in patients with advanced HF. However, patients with a >or=9-mm Hg decrease had no better survival than patients in the control group, who had limited changes in hemodynamics. Thus, improvement in hemodynamics may not predict the overall effect of a drug.

Aged↗

PubMed2002

Genetics of chronic lymphocytic leukemia: genomic aberrations and V(H) gene mutation status in pathogenesis and clinical course.

The genetic characterization of chronic lymphocytic leukemia (CLL) has made significant progress over the past few years. While conventional cytogenetic analyses only detected chromosome aberrations in 40-50% of cases, new molecular cytogenetic methods, such as fluorescence in situ hybridization (FISH), have greatly enhanced our ability to detect chromosomal abnormalities in CLL. Today, genomic aberrations are detected in over 80% of CLL cases. Genes potentially involved in the pathogenesis were identified with ATM in a subset of cases with 11q deletion and p53 in cases with 17p13 deletion. For the most frequent aberration, the deletion 13q14, candidate genes have been isolated. Genetic subgroups with distinct clinical features have been identified. 11q deletion is associated with marked lymphadenopathy and rapid disease progression. 17p deletion predicts for treatment failure with alkylating agents, as well as fludarabine and short survival times. In multivariate analysis 11q and 17p deletions provided independent prognostic information. Recently, another important issue of genetic risk classification in CLL was identified with the mutation status of the immunoglobulin variable heavy chain genes (V(H)). CLL cases with unmutated V(H) show more rapid disease progression and shorter survival times. Whether CD38 expression can serve as a surrogate marker for V(H) mutation status is currently discussed controversially. V(H) mutation status and genomic abnormalities, such as 17p and 11q deletion, have recently been shown to be related to each other, but were of independent prognostic information in multivariate analysis. Moreover, genomic aberrations and V(H) mutation status appear to give prognostic information irrespective of the clinical stage and may therefore allow a risk assessment for individual patients early in the course of their disease.

Chromosome Aberrations↗

PubMed2000

Prediction of short cardiovascular variability signals based on conditional distribution.

A new approach measuring the predictability of a process is proposed. The predictor is defined as the median of the distribution conditioned by a sequence of L - 1 previous samples (i.e., a pattern). A function referred to as the corrected mean squared predictor error is defined to prevent the perfect adequacy to the data (i.e., the decrease to zero of the prediction error), thus avoiding to divide the whole set of data in learning and test sets. This function exhibits a minimum and this minimum is taken as a measure of predictability of the series. The use of the minimization procedure avoids to fix a priori the pattern length L. This approach permits one a reliable measure of predictability on short data sequences (around 300 samples). Moreover, this method, in connection with a surrogate data approach, is useful to detect nonlinear dynamics. The analysis indicates that, in simulated and real data, predictability and nonlinearity measures provide different information. The application of this approach to the analysis of cardiovascular variability series of the heart period (RR interval) and systolic arterial pressure (SAP) shows: 1) SAP series is more predictable than RR interval series; 2) predictability of the RR interval series is larger during tilt, during controlled respiration at 10 breaths/min (bpm) and after high-dose administration of atropine; 3) SAP series is dominated by linear correlation; 4) RR interval series exhibits nonlinear dynamics during controlled respiration at 10 bpm and after low-dose administration of atropine, while it is linear during sympathetic activation produced by tilt and after peripheral parasympathetic blockade caused by high-dose administration of atropine.

Adult↗

PubMed2002

Investigation of pulmonary function among employees exposed to low levels of monomeric isocyanates and solvents at an automobile finishings plant.

There have been reports in the literature of decrements in pulmonary function associated with long-term, low-level monomeric isocyanate exposure combined with solvent exposure. This cross-sectional study examines the relationship between these exposures and pulmonary function in an automobile paint and coating (finishes) plant. A job exposure matrix was developed for isocyanate and solvent exposure; years in a work task were used as a surrogate for exposure. Recent pulmonary function tests were used as the outcome variables; specifically the difference between predicted and actual FEV1 and FVC. The results of the analysis demonstrated no statistically significant relationship between combined isocyanate and solvent exposure and decline in pulmonary function. There was a statistically significant negative correlation between solvent exposure and FEV1 and FVC.

Adult↗

PubMed2004

Growth hormone (GH) peaks versus areas under the curve in the diagnosis of adult GH deficiency: analysis of the variables provided by the GHRH + GHRP-6 test.

BACKGROUND: The diagnosis of growth hormone deficiency (GHD) relies on provocative tests of GH reserve. The aim in these tests is to obtain an objective, biochemical-based, measure of gland function, but clinicians and researchers rely on the GH peak, as a surrogate of the 24-hour pituitary secretion. However, on a mathematical basis the area under the secretory curve (AUC) should be more valid for this evaluation. OBJECTIVES: To validate which variable provided by a provocative test of GH secretion is mathematically more robust for supporting the clinical diagnosis. Adult normal subjects and GHD patients were challenged with the combined stimulus GHRH + GHRP-6. The diagnostic efficacy of the GH peak, and the AUC were compared by the receiver operating characteristic (ROC) curve methodology. PATIENTS AND METHODS: 146 patients with GH deficiency due to organic pituitary disease and 184 healthy subjects were administered GHRH 1 microg/Kg iv, plus GHRP-6 1 microg/Kg iv, and GH was determined. Four variables were studied: (a) the GH peak; (b) the "standard" AUC, (c) the "stimulated" AUC and (d) the basal value, used as internal control. RESULTS: Under ROC curve analysis, the basal variable was devoid of diagnostic capability, while the other variables performed strikingly well, the ROC curve area for the GH peak was 0.9997; and for the AUC 0.9993, with no statistical differences. CONCLUSIONS: The variables provided by measuring the GH peak and the area under the curve were similarly effective for diagnosis, although on clinical grounds, the peak was more convenient as needed no calculation. If results for other test were similar the time-honored method of measuring the GH peak could be considered mathematically validated.

Adult↗

PubMed2006

Morphometric sum optical density as a surrogate marker for ploidy status in prostate cancer: an analysis in 180 biopsies using logistic regression and binary recursive partitioning.

We sought to identify morphometric descriptors predictive of nondiploidy in prostatic adenocarcinoma on prostate needle biopsies using logistic regression (LR) and binary recursive partitioning (BRP) and compare the equivalence of both methods. A total of 180 prostate needle biopsies diagnosed as prostatic adenocarcinoma were selected. Deoxyribonucleic acid ploidy and morphometry were performed separately on Feulgen-stained sections from these biopsies using the CAS-200 system and Nuclear Morphometry Suite, respectively. Seven morphometric predictors were tested as predictor variables, including nuclear area, circularity, elongation, sum optical density (OD), configuration run length, coefficient of variation (CV), and angularity. Logistic regression (LR) identified a two-parameter model including sum OD and circularity that had a 93.9% overall correct prediction rate (area under curve=0.950; 95% CI: 0.913, 0.987). A reduced model including only sum OD was equally good without any significant loss of predictive accuracy (93.3% correct overall classification rate). BRP also selected sum OD as the most predictive parameter; a sum OD cut-off of 7.73 in this model identified 93.3% of the nondiploid cases correctly. Morphometric OD can be used as a surrogate marker of nondiploidy. LR and BRP models are both equivalent in identifying and correctly classifying nondiploid cases of prostate cancer using sum OD as the predictor variable.

Adenocarcinoma↗

PubMed1990

The relationship of daily mortality to suspended particulates in Santa Clara County, 1980-1986.

This paper explores the relationship between daily mortality and suspended particulates in Santa Clara County, CA, for years 1980 to 1986. An association was found between high particulate concentrations and increased mortality. This association persists after adjustment for temperature, relative humidity, year, and seasonality. Contrary to expectation, the magnitude of the particulate effect appears the same or larger than that estimated for London, despite Santa Clara County's cleaner air. The persistence of an effect at these lower particulate concentrations suggests that the particulate variable may be acting as a surrogate for some constituent particles, such as acid aerosols.

Age Factors↗

PubMed2006

[Definition of low threshold volumes for quality assurance: conceptual and methodological issues involved in the definition and evaluation of thresholds for volume outcome relations in clinical care].

In a large number of mostly retrospective association studies, a statistical relationship between volume and quality of health care has been reported. However, the relevance of these results is frequently limited by methodological shortcomings. In this article, criteria for the evidence and definition of thresholds for volume-outcome relations are proposed, e.g. the specification of relevant outcomes for quality indicators, analysis of volume as a continuous variable with an adequate case-mix and risk adjustment, accounting for cluster effects and considering mathematical models for the derivation of cut-off values. Moreover, volume thresholds are regarded as surrogate parameters for the indirect classification of the quality of care, whose diagnostic validity and effectiveness in improving health care quality need to be evaluated in prospective studies.

Confounding Factors, Epidemiologic↗

PubMed1998

Dose-response characteristics of uterine responses in rats exposed to estrogen agonists.

Assays for uterine response have played major roles in developing an understanding of estrogen-mediated processes and for identifying compounds with hormonal activity. Data from assays measuring increases in uterine wet weight in rats were evaluated in terms of their dose-response characteristics. Analysis using a Hill equation found inconsistent estimates for the ED50 (concentration giving half-maximal response) and n (steepness of response) among the assays. This variability reflects disparate assay protocols and limitations of the dose-response data collected in the experiments. Although uterine wet weight is easily measured, it arises from several physiological processes (e.g., water retention, cell proliferation). This contributes to the assay variability with different protocols. The potential use of the Hill equation for dose-response analysis to estimate a benchmark dose was also considered using these data sets as surrogates for receptor-mediated toxicological effects. Strengths and weaknesses were identified, but overall the Hill equation should likely become a favored option for determining a benchmark dose, particularly when a data set demonstrates a maximal response. For screening purposes, empirical analysis using the Hill equation provides adequate information for classifying and prioritizing compounds. To develop an understanding of how incremental exposures to compounds with estrogen agonist activities would affect intact adult females, quantitative analyses are required that account for the pharmacokinetics of estradiol and subsequent interactions of the receptor complexes in regulating the responses.

Animals↗

PubMed1999

Anatomic changes after endovascular grafting for aneurysmal disease.

Long-term follow-up of controlled clinical trials of endovascular grafting for aortic aneurysms will provide data on the safety and efficacy of this new treatment to reduce morbidity and mortality compared with standard treatment. It will be several years before this information will be available, and careful analysis of surrogate markers for clinical success has value for predicting long-term outcome. One essential surrogate marker is aortic aneurysm diameter, which has traditionally been the most important variable in calculating rupture risk, and multiple studies have shown that aneurysms shrink after complete endovascular exclusion. Furthermore, measurements of aortic neck size and aortic length has shown interesting patterns that may affect the durability of endovascular repair and, thus, may suggest potential strategies for the design of future devices.

Aorta↗

PubMed2004

Heart rate analysis in normal subjects of various age groups.

BACKGROUND: Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. Linear parameters, Power spectral indice (LF/HF) is calculated with nonlinear indices Poincare plot geometry(SD1,SD2), Approximate Entropy (ApEn), Largest Lyapunov Exponent (LLE) and Detrended Fluctuation Analysis(DFA). The results show that, with aging the heart rate variability decreases. In this work, the ranges of all linear and nonlinear parameters for four age group normal subjects are presented with an accuracy of more than 89%. As a pre-analysis step, the HRV data is tested for nonlinearity using surrogate data analysis and the results exhibited a significant difference in the ApEn, LLE, SD1/SD2 and DFA parameters of the actual data and the surrogate data. METHODS: The heart rate is analyzed using the various time domain parameters, frequency domain parameter and nonlinear parameters like Poincare geometry, ApEn, LLE and DFA. RESULTS: In this work, the different linear and nonlinear parameters evaluated show a particular range for various cardiac abnormalities. And the results of these were subjected to 't' test with more than 89% confidence interval giving excellent 'p' values in all cases. CONCLUSIONS: Heart rate variability (HRV) signal can be used as a reliable indicator of state of the heart. It becomes less random with the aging(less chaotic). This is evaluated by using various time domain, frequency domain and nonlinear parameters like SD1/SD2, ApEn, LLE alphas and alphal. Different ranges of non-linear parameters for various age groups are presented with 'p' value < or = 0.12.

Adolescent↗

PubMed1995

Cumulative exposure to inorganic lead and neurobehavioural test performance in adults: an epidemiological review.

OBJECTIVES: To evaluate the current evidence that cumulative exposure to inorganic lead is associated with decreased performance in neurobehavioural tests in adults. METHODS: 21 unique studies were reviewed from 28 published manuscripts. An algorithm was developed to determine the usefulness of each study on the basis of exposure assessment, control of confounding variables, methods of subject selection, test conditions, and data analysis. Highest emphasis was placed on the use of cumulative measures of exposure or absorption. RESULTS: Only three studies used a measure of cumulative exposure to or absorption of lead, and two others used duration of exposure as a surrogate for cumulative exposure. All other studies used a measure that did not adequately estimate cumulative exposure to lead, most often current blood lead concentration. 20 of the studies controlled for age as a confounding variable, although in several studies the possibility for residual confounding by age remained. 16 studies controlled for intellectual ability before exposure; all of them used educational level for this purpose. Of the five studies that used direct or surrogate measures of cumulative exposure to or absorption of lead, two were thought to be of low usefulness because of inadequate duration of exposure. The three remaining studies found stronger associations of neurobehavioural performance with recent exposure measures than with those of cumulative exposure. CONCLUSION: The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioural tests in adults. The current evidence is flawed because of inadequate estimation of cumulative exposure to or absorption of lead and inadequate control for age and intellectual ability before exposure.

Age Factors↗

PubMed2006

Multiplex short tandem repeat DNA analysis confirms the accuracy of p57(KIP2) immunostaining in the diagnosis of complete hydatidiform mole.

Detailed histopathologic examination remains to be the basis for the diagnosis of hydatidiform mole (HM). However, poor sampling, necrosis, and earlier uterine evacuation can lead to uncertainty in the diagnosis. Also, the criteria are subjective, resulting in considerable interobserver variability. The p57(KIP2) gene is paternally imprinted and maternally expressed, and the presence of its protein product serves as a surrogate marker for the nuclear maternal genome. Because a complete HM (CHM) is the only type of conceptus lacking a maternal contribution, p57(KIP2) immunostaining is correspondingly absent, whereas it is present in CHM mimics. Although analysis of DNA microsatellite polymorphisms is a reliable method for the diagnosis and classification of HM, it is not universally available. To assess the relative accuracy of p57(KIP2) immunostaining and molecular diagnosis by nuclear DNA microsatellite polymorphisms in discriminating CHM from its mimics, we analyzed archival tissue from 33 case patients (7 with a definitive diagnosis of CHM, 16 with a possible diagnosis of HM, and 10 with normal placentas) by both methods. Concordant results were obtained in all cases, and p57(KIP2) immunostaining accurately identified all cases of CHM from the groups with a definitive or possible diagnosis of HM. p57(KIP2) immunohistochemistry is a time- and cost-effective means of distinguishing CHM from its mimics in challenging cases.

Alleles↗

PubMedDate not supplied

Estimating analytical variances in measurement of polycyclic aromatic hydrocarbons and application to monitoring contaminants in American lobster (Homarus americanus).

A method is presented for estimating replicate polycyclic aromatic hydrocarbon (PAH) concentrations in American lobster (Homarus americanus) digestive gland tissue based on recoveries of added perdeuterated surrogates from a single satisfactory analysis. PAH concentrations demonstrated a large interanimal variance, even in specimens captured at the same time in the same place. Principal component analysis showed that the variability of the total system of biological variables (carapace length, lobster weight, and digestive gland weight) could be adequately summarized by the first principal component alone in each data set. Ranks provide ordered classification of individuals, allowing data analysis by statistical methods for continuous variables (i.e., analysis of variance). PAH concentrations in individual lobsters were generally highly sensitive to animal size, sex, and fishing area. Efficient monitoring would result from analyzing individual animals of a single sex from a study area, using as small a geographical study area as possible, measuring a single biological variable, and using individual specimens of as narrow a size range as possible.

Analysis of Variance↗

PubMed2005

Aging and nonlinear heart rate control in a healthy population.

In recent years more studies are using nonlinear dynamics to describe cardiovascular control. Because of the large dispersion of physiological data, it is important to have large studies with both male and female participants to establish a range of physiological healthy values. This study investigated the effect of gender and age on nonlinear indexes. Nonlinear scaling properties were studied by using 1/f slope (where f is frequency), fractal dimension, and detrended fluctuation analysis short- and long-term correlations (DFAalpha(1) and DFAalpha(2), respectively). Nonlinear complexity was described with correlation dimension (CD), Lyapunov exponent (LE), and approximate entropy (ApEn). The population consisted of 135 women and 141 men (age, 18-71 yr). Twenty-four hour ECG recordings were obtained by using Holter monitoring. The recordings were split into daytime (8 AM-9 PM) and nighttime (11 PM-6 AM). A day-night variation was present in all nonlinear heart rate variability (HRV) indexes, except for the CD in the female population. During the night the percentage of CD values of surrogate data files differing from the CD value of the original data increased. All nonlinear indexes were significantly correlated with age. Deeper analysis per age category of 10 yr showed a stabilization in the age decline of the fractal dimension and ApEn at the age of > or =40 yr. The vagal pathways seemed to be more involved in the generation of nonlinear fluctuations. Higher nonlinear behavior was evident during the night. No clear difference between men and women was found in the nonlinear indexes. Nonlinear indexes decline with age. This can be related to the concept of decreasing autonomic modulation with advancing age.

Adult↗

PubMed2006

Trauma Associated Severe Hemorrhage (TASH)-Score: probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma.

BACKGROUND: To develop a simple scoring system that allows an early and reliable estimation for the probability of mass transfusion (MT) as a surrogate for life threatening hemorrhage following multiple trauma. METHODS: Potential clinical and laboratory variables documented in the Trauma Registry of the German Trauma Society (DGU) (1993-2003; n=17,200) were subjected to univariate and multivariate logistic regression analysis to predict the probability for MT. RESULTS: Clinical and laboratory variables available from data sets were screened for their association with mass transfusion. MT was defined by transfusion requirement of >or=10 units of packed red blood cells from emergency room (ER) to intensive care unit admission. Seven independent variables were identified to be significantly correlated with an increased probability for MT: systolic blood pressure (<100 mm Hg=4 pts, <120 mm Hg=1 pt), hemoglobin (<7 g/dL=8 pts, <9 g/dL=6 pts, <10 g/dL=4 pts, <11 g/dL=3 pts, and <12 g/dL=2 pts), intra-abdominal fluid (3 pts), complex long bone and/or pelvic fractures (AIS 3/4=3 pts and AIS 5=6 pts), heart rate (>120=2 pts), base excess (<-10 mmol/L=4 pts, <-6 mmol/L=3 pts, and <-2 mmol/L=1 pt), and gender (male=1 pt). These variables were incorporated into a risk score, the Trauma Associated Severe Hemorrhage Score (TASH-Score, 0-28 points). Performance of the score was tested with respect to discrimination, precision, and calibration. Increasing TASH-Score points were associated with an increasing probability for MT. CONCLUSION: The TASH-Score is an easy-to-use scoring system that reliably predicts the probability for MT after multiple trauma. Taken as a surrogate for life threatening bleeding calculation may focus attention on relevant variables indicative for risk and impact strategies to stop bleeding and stabilize coagulation in acute trauma care.

Adult↗

PubMedDate not supplied

Risk factors for tuberculosis among human immunodeficiency virus-infected persons. A case-control study in Belo Horizonte, Minas Gerais, Brazil (1985-1996).

The objective of this study was to identify tuberculosis risk factors and possible surrogate markers among human immunodeficiency virus (HIV)-infected persons. A retrospective case-control study was carried out at the HIV outpatient clinic of the Universidade Federal de Minas Gerais in Belo Horizonte. We reviewed the demographic, social-economical and medical data of 477 HIV-infected individuals evaluated from 1985 to 1996. The variables were submitted to an univariate and stratified analysis. Aids related complex (ARC), past history of pneumonia, past history of hospitalization, CD4 count and no antiretroviral use were identified as possible effect modifiers and confounding variables, and were submitted to logistic regression analysis by the stepwise method. ARC had an odds ratio (OR) of 3.5 (CI 95% - 1.2-10.8) for tuberculosis development. Past history of pneumonia (OR 1.7 - CI 95% 0.6-5.2) and the CD4 count (OR 0.4 - CI 0. 2-1.2) had no statistical significance. These results show that ARC is an important clinical surrogate for tuberculosis in HIV-infected patients. Despite the need of confirmation in future studies, these results suggest that the ideal moment for tuberculosis chemoprophylaxis could be previous to the introduction of antiretroviral treatment or even just after the diagnosis of HIV infection.

AIDS-Related Complex↗

PubMed2003

Quantitative image analysis: software systems in drug development trials.

Multi-dimensional image analysis is being used increasingly to arrive at surrogate end-points for drug development trials. Various imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound are used to analyze treatments for diseases such as cancer, multiple sclerosis, osteoarthritis, and Alzheimer's disease. However, extracting information from images can be tedious and is prone to high user variability. The medical image analysis community is moving towards advanced software systems specifically designed for drug development trials. These systems can automatically identify the anatomy of interest in medical images (segmentation methods), can compare the anatomy over time or between patients (registration methods) and allow the quantitative extraction of anatomical features and the integration of the data and results into a database management system, automatically tracking the changes made to the data (audit trail generation). In this article, we present a case study using a prototype system that is used for quantifying multiple sclerosis lesions from multivariate MRI.

Clinical Trials as Topic↗