SEARCH · PubMed Health

Results for “Surrogate variables analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1997

Prognosis of idiopathic membranous nephropathy: a methodologic meta-analysis.

Results in studies on prognosis and treatment of membranous nephropathy are conflicting. The aim of this investigation was to analyze the methodology of the existing research and to identify sources of these conflicting results. Studies published on prognosis of membranous nephropathy from 1970 to 1995 were identified using a Medline database literature search. The criteria for inclusion in the methodologic analysis were: (1) original article; (2) cohort study or clinical trial with > or = 50 adults; (3) zero time near the diagnostic renal biopsy; and (4) follow-up > or = six months. Ten well-accepted methodologic standards for prognostic research were applied to each study and the compliance was evaluated. Among the 26 studies that met the inclusion criteria, the median number of standards fulfilled was 4 and the highest was 7. The proportion of studies adhering to the individual standards was: (1) adequate diagnostic criteria, 35%; (2) definite end point, 46%; (3) adequate analysis of a surrogate end point, 52%; (4) analysis of baseline severity, 0%; (5) indication of baseline frequency for candidate predictors, 35%; (6) reproducible classification of predictors, 85%; (7) multivariable analysis, 50%; (8) identification of the variables' importance in multivariable analysis, 38%; (9) evaluation of the effect of treatment on predictors, 19%; and (10) adequate analysis of censored patients, 58%. We conclude that basic methodologic principles have frequently been disregarded. The consideration of these standards in future research can improve the interpretability and applicability of results and help reconcile conflict when results are compared among different studies.

Adult↗

PubMed1996

A DNA repair abnormality specific for rearranged immunoglobulin variable genes in germinal center B cells.

The somatic hypermutation mechanism produces high-rate mutagenesis specifically targeted to rearranged immunoglobulin (Ig) variable (V) gene segments during the germinal center (GC) stage of B lymphocyte differentiation. The mechanism of this process remains uncertain, partly due to the lack of a direct assay for hypermutation activity. In this study, a gene-specific DNA repair assay was used to compare the rate and quality of DNA repair in the mantle zone (MZ) and GC B cells at rearranged and unrearranged Ig V genes. GC B cells were distinguished from MZ B cells by a retarded repair rate specific for rearranged Ig V genes. In addition, a unique feature of GC cells after DNA repair was the appearance of predominant mutations in rearranged Ig VH5 gene PCR products. These predominant mutations also occurred in natural mutants of VH5 genes. However, repair-associated mutations reflected, at least in part, "template-jumping" during amplification of the residually damaged genomic template. Overall, these findings reflect a repair abnormality associated with the hypermutation process by the criteria of sequence- and B cell stage-specificity. We conclude that locus-specific retardation of DNA repair is a component of the hypermutation mechanism. RFLP or SSCP analysis provides a simple assay to monitor this repair abnormality as a surrogate biochemical marker for hypermutation during B cell differentiation.

B-Lymphocytes↗

PubMed2006

A robust ratio metric method for analysis of Zap-70 expression in chronic lymphocytic leukemia (CLL).

Since Zap-70 expression in chronic lymphocytic leukemia (CLL) cells correlates with a lack of somatic mutation of the immunoglobulin variable heavy chain (IgVH) genes, it has been proposed as a surrogate marker for disease prognosis. However, published studies of Zap-70 expression have used different commercial antibodies and analytic strategies. This study was undertaken to determine if any strategy was broadly applicable in a clinical flow cytometry laboratory. Expression of Zap-70 was determined in 37 CLL patients using four different commercial antibodies. T, NK, and CLL cells were identified by immunophenotyping along with Zap-70 expression. Data was analyzed in terms of both percent of CLL cells expressing Zap-70 and the ratio of Zap-70 expression in CLL cells compared to that in T + NK cells. Three Zap-70 antibodies showed wide ranges of Zap-70 expression as a percentage of tumor cells, while a fourth gave consistently elevated results. Comparing the percent Zap-70 expression with any two antibodies gave poor correlations (r(2) = 0.45-0.63). Our results indicated that the previous analytical strategies were not reproducible. A ratio metric is proposed, which gave better correlations (r(2) as high as 0.95) and would allow separation of CLL patients with elevated or decreased Zap-70 expression.

Antibodies, Monoclonal↗

PubMed2001

Ultrasound velocity and cortical bone characteristics in vivo.

Axial transmission of ultrasound along cortical bone may reflect a combination of material and structural properties of long bone cortices. The goal of this study was to determine the association of speed of sound (SOS) with cortical density (CoD), cortical wall thickness (CWT), and total cortical area (CoA). Quantitative ultrasound (QUS) and peripheral quantitative computed tomography (pQCT) were used to measure the above variables in the distal third of radius and the midshaft of tibia in 51 postmenopausal women aged 62 to 71 years. Univariate regression analysis showed that the site-specific CoD accounted for 34% of the variability in the radial SOS and 29% of that in the tibial SOS (p < 0.001 both). SOS was only moderately associated with radial CWT (R2 = 0.14, p < 0.05) and CoA (R2 = 0.12, p < 0.05), but not with tibial CWT nor CoA. After controlling for CoD, these dimension-related associations disappeared. Stepwise multiple regression analysis showed that CoD was the only significant determinant of radial SOS (adjusted R2 = 0.31), whereas for tibia, not only CoD but also the years since menopause were associated with SOS (adjusted R2 = 0.41). In conclusion, out of the studied macroscopic cortical variables, CoD (an apparent surrogate for material properties of bone) was the only determinant of SOS measured in vivo at radial and tibial shafts. The key question that still needs to be answered is whether the SOS information obtained from the peripheral long bone cortical shafts can be translated to describe the mechanical competence and quality of clinically pertinent bones (e.g. proximal femur) of a given individual.

Aged↗

PubMed1994

Statistical analysis of proliferative index data in clinical trials.

Measurements of proliferative activity in colonic epithelial cells are being used as surrogate endpoints in clinical trials for colon cancer prevention. Proliferative index data exemplify an important type of clinical trial endpoint. The outcome variable is a proportion in which the denominator is an ancillary statistic and in which measurement error and technician judgement are important sources of variability. The paper proposes a statistical model for a repeated measures clinical trial with this type of endpoint, in the context of proliferative activity data. The model is a two-stage random effects linear model in the log scale. In addition to fixed effects covariates, it explicitly incorporates two major sources of variability: the number of epithelial cells counted and the reader effect. Although the resulting likelihood is complicated, one can fit an approximate likelihood with minimal loss of efficiency using standard packages. We apply the model to a pilot randomized clinical trial.

Cell Division↗

PubMedDate not supplied

Estimating ground water recharge from topography, hydrogeology, and land cover.

Proper management of ground water resources requires knowledge of the rates and spatial distribution of recharge to aquifers. This information is needed at scales ranging from that of individual communities to regional. This paper presents a methodology to calculate recharge from readily available ground surface information without long-term monitoring. The method is viewed as providing a reasonable, but conservative, first approximation of recharge, which can then be fine-tuned with other methods as time permits. Stream baseflow was measured as a surrogate for recharge in small watersheds in southeastern Wisconsin. It is equated to recharge (R) and then normalized to observed annual precipitation (P). Regression analysis was constrained by requiring that the independent and dependent variables be dimensionally consistent. It shows that R/P is controlled by three dimensionless ratios: (1) infiltrating to overland water flux, (2) vertical to lateral distance water must travel, and (3) percentage of land cover in the natural state. The individual watershed properties that comprise these ratios are now commonly available in GIS data bases. The empirical relationship for predicting R/P developed for the study watersheds is shown to be statistically viable and is then tested outside the study area and against other methods of calculating recharge. The method produces values that agree with baseflow separation from streamflow hydrographs (to within 15% to 20%), ground water budget analysis (4%), well hydrograph analysis (12%), and a distributed-parameter watershed model calibrated to total streamflow (18%). It has also reproduced the temporal variation over 5 yr observed at a well site with an average error < 12%.

Climate↗

PubMed2001

Stochastic structures between quantity and quality responses of rainfall-runoff at an upland agricultural watershed.

The causality between hydrologic parameters and water quality variations has been studied for a small upland agricultural watershed using a time-series analysis approach. The stage at the outlet of the watershed, which is a proxy for the outflow, and the average saturation deficit, which is a surrogate for the groundwater level, were used as hydrologic variables. The stages were measured at a triangular weir at the watershed outlet. The saturation deficits were obtained by means of a rainfall-runoff simulation model for agricultural upland watersheds (an extended version of TOPMODEL). Sequential water quality data were also collected at the watershed outlet. A systematic procedure for testing the causality between the hydrologic and water quality time-series is presented and used to investigate possible relationships between the two systems. The stochastic structure of a causality between hydrologic and water quality systems is shown. This stochastic structure is associated not only with the transport pathways (surface or subsurface) of each water quality parameter but also with the characteristics of the rainfall events.

Agriculture↗

PubMed2003

Nonlinear dynamics indicates aging affects variability during gait.

OBJECTIVE: To investigate the nature of variability present in time series generated from gait parameters of two different age groups via a nonlinear analysis. DESIGN: Measures of nonlinear dynamics were used to compare kinematic parameters between elderly and young females. BACKGROUND: Aging may lead to changes in motor variability during walking, which may explain the large incidence of falls in the elderly. METHODS: Twenty females, 10 younger (20-37 yr) and 10 older (71-79 yr) walked on a treadmill for 30 consecutive gait cycles. Time series from selected kinematic parameters of the right lower extremity were analyzed using nonlinear dynamics. The largest Lyapunov exponent and the correlation dimension of all time series, and the largest Lyapunov exponent of the original time series surrogated were calculated. Standard deviations and coefficient of variations were also calculated for selected discrete points from each gait cycle. Independent t-tests were used for statistical comparisons. RESULTS: The Lyapunov exponents were found to be significantly different from their surrogate counterparts. This indicates that the fluctuations observed in the time series may reflect deterministic processes by the neuromuscular system. The elderly exhibited significantly larger Lyapunov exponents and correlation dimensions for all parameters evaluated indicating local instability. The linear measures indicated that the elderly demonstrated significantly higher variability. CONCLUSIONS: The nonlinear analysis revealed that fluctuations in the time series of certain gait parameters are not random but display a deterministic behavior. This behavior may degrade with physiologic aging resulting in local instability. RELEVANCE: Elderly show increased local instability or inability to compensate to the natural stride-to-stride variations present during locomotion. We hypothesized that this may be the one of the reasons for the increases in falling due to aging. Future efforts should attempt to evaluate this hypothesis by making comparisons to pathological subjects (i.e. elderly fallers), and examine the sensitivity and specificity of the nonlinear methods used in this study to aid clinical assessment.

Adult↗

PubMed2005

Hyperinsulinemia predicts hepatic fat content in healthy individuals with normal transaminase concentrations.

Although the prevalence of insulin resistance (IR) and compensatory hyperinsulinemia (CH) is increased in patients with nonalcoholic fatty liver disease, the role of IR/CH in regulation of hepatic fat content in healthy volunteers with normal concentrations of alanine transaminase (ALT) has not been defined. To address this issue, hepatic fat content was quantified by ultrasound in 69 (30 men, 39 women) healthy individuals, without known risk factors for liver disease and with plasma ALT concentrations of less than 30 U/L. Experimental variables quantified included body mass index, waist circumference, systolic and diastolic blood pressures, and fasting plasma glucose, fasting plasma insulin (FPI), and lipid concentrations. Subjects were classified as having no (55%), mild (27%), or moderate to severe (18%) hepatic steatosis on the basis of the ultrasound results. Statistically significant (P < .05-.001) correlations (Spearman rho values) existed between liver fat content and ALT (0.26), body mass index (0.52), waist circumference (0.50), systolic blood pressure (0.28), diastolic blood pressure (0.27), fasting plasma glucose (0.47), FPI (0.56), triglycerides (0.30), and high-density lipoprotein cholesterol (-0.35). Multivariate general discriminant analysis and multiple linear regression analysis indicated that FPI was the only independent predictor (P < .001) of both liver fat content and ALT concentrations. Fasting plasma insulin (a surrogate estimate of IR/CH) predicts hepatic fat content and ALT in healthy volunteers with normal transaminase concentrations, independently of the other anthropometric and metabolic variables measured.

Aged↗

PubMed2003

A multitrial analysis for revealing significant corticocortical networks in magnetoencephalography and electroencephalography.

We present an MEG/EEG framework to reveal statistically significant brain areas engaged in the same cognitive process across trials without resort to averaging procedures. The variability of neuronal responses is assumed to take place only in the reconstructed time series of cortical sources and not in their positions. This hypothesis allows the use of the surrogate data method to detect recurrently active brain areas across trials adjusted with any cortically constrained focal MEEG inverse solution. Results obtained from synthetic data show that considering several trials enhances the accuracy of the source localisation. We apply this approach on MEG data recorded during a simple visual stimulation. The considered stimulus is frequency tagged in order to reveal the neural network correlated to its perception using phase synchronisation analysis. The results show consistent patterns of distributed synchronous networks centred on occipital areas.

Adult↗

PubMedDate not supplied

Uses of epidemiologic information in pollution episode management.

Epidemiologic information and analysis are essential for the process of health risk assessment and management in pollution episodes. Recognition of causal associations between exposure and disease requires an understanding of the nature of data upon which such associations are based and of the limitations that affect such data. Data concerned with disease detection are often affected by long and variable latencies, clinical nonspecificity, low frequencies (small population sizes), and reporting biases. Data concerned with measuring exposures must take into account pathway uncertainties, probable low dose levels, inability to develop dose-response information, and the frequent necessity to rely on indirect surrogates for dose estimation. Where such difficulties can be overcome, epidemiologic analysis can be decisive in identifying causal relationships. More often, data limitations require more limited conclusions. Case studies from New York, Michigan, South Carolina, and Massachusetts illustrate the impact of these principles on the process of health risk assessment.

Data Collection↗

PubMed2004

The genomics of gene expression.

The study of gene regulation on a genomic scale has been constrained by the modest pace with which new trans-regulatory factors have been identified and by the fact that cis-regulatory sequences have to date been described even in part for only a small fraction of vertebrate genes. An indirect approach for assessing the significance of cis- and trans-regulatory mechanisms on a global scale is to utilize gene expression as a surrogate for transcriptional regulation and to combine genome-scale transcriptional profiling with studies of genetic variation, classical genetic techniques such as linkage analysis, and examination of allelic expression patterns that reveal cis-regulatory variability. A number of recent studies employing these methods provide insight into questions of central importance to our understanding of the larger role of transcriptional regulation in the organization of the human and other complex genomes.

Animals↗

PubMed2002

Evidence for fractal correlation properties in variations of peripheral arterial tone during REM sleep.

Previous studies utilizing detrended fluctuation analysis (DFA) of heart rate variability during sleep revealed a higher fractal exponent during rapid eye movement (REM) sleep than non-REM sleep. The aim of this study was to determine whether the same difference exists in the variations of peripheral arterial tone (PAT). Finger pulse wave measured by a novel plethysmographic technique was monitored during sleep in 12 chronic heart failure patients, 8 heavy snorers, and 12 healthy volunteers. For each subject, at least two 15-min time series were constructed from the interpulse intervals and from pulse wave amplitudes during REM and non-REM sleep. Fractal scaling exponents of both types of time series were significantly higher for REM than non-REM sleep in all groups. In each of the groups and in both sleep stages, the fractal scaling exponents based on pulse wave amplitude were significantly higher than those based on pulse rate variability. A repeat of the analysis for short-, intermediate-, and long-term intervals revealed that the fractal-like exponents were evident only in the short- and intermediate-term intervals. Because PAT is a surrogate of sympathetic activation, our results indicate that variations in sympathetic activation during REM sleep have a fractal-like behavior.

Adult↗

PubMed2005

[DNA adducts as biological markers for human exposure to polycyclic aromatic compounds].

Polycyclic Aromatic Hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention or preventive study. The successful applicability of DNA adducts as early endpoints depends on several criteria: (1) Adduct levels in easily accessible surrogate tissues should reflect adduct levels in target tissues (2) Toxic-kinetics and the temporal relevance should be properly defined (3) Sources of inter and intra individual variability must be know and controllable (4) Adduct analysis must have advantages as compared to other markers of PAH exposure. Higher proportions of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposure. Furthermore, DNA adducts levels varied according to changes in exposure. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Intra-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH metabolism. DNA adducts measurements have three advantages over traditional exposure assessment: (1) they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over longer periods of time (2) Biological monitoring of DNA adducts accounts for all exposure routes (3) DNA adduct may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. There is a sufficiently large scientific basis to justify the application of DNA adduct measurements as biomarkers in exposure assessment. However, their use in risk assessment requires further investigation.

Biological Transport↗

PubMed2003

High vibration perception threshold and autonomic dysfunction in hemodialysis patients with intradialysis hypotension.

BACKGROUND: Intradialysis hypotension is a common problem among hemodialysis patients. Some studies have shown that autonomic neuropathy could be a major cause of intradialysis hypotension, whereas others have not. Furthermore, whether there are parallel changes in the autonomic nervous system and somatic nerves remains unclear. METHODS: We investigated the autonomic and peripheral nervous functions of 12 chronic hemodialysis patients who suffered from intradialysis hypotension, and of 12 age- and sex-matched hemodialysis patients who had stable blood pressure during hemodialysis. We used spectral analysis of their heart rate variability and systemic vascular resistance to evaluate autonomic functions. Vibrameter and nerve conduction studies to assess peripheral nervous function were also performed. Low-frequency/high-frequency ratio power index was used as a surrogate of sympathovagal balance. RESULTS: The power index rose progressively in the control group and reached significantly high levels at hour 4 compared to the basal values (3.7 +/- 0.5 vs. 2.1 +/- 0.3; P < 0.05). However in the group prone to hypotension, the power index remained almost unchanged. In addition, their systemic vascular resistance was lower than that in the control group (13.7 +/- 1.8 vs. 22.3 +/- 2.6 Wood units; P < 0.05). The vibration perception thresholds of the index finger and great toe were significantly higher in the group prone to hypotension (4.7 +/- 0.7 vs. 2.2 +/- 0.3 vibration units and 3.1 +/- 0.4 vs. 1.5 +/- 0.2 vibration units, respectively; both P < 0.05). CONCLUSION: We found that more severe damage to autonomic and peripheral nervous system occurred in patients prone to hypotension.

Adult↗

PubMed2000

Linear and nonlinear time series analysis of the black hole candidate cygnus X-1

We analyze the variability in the x-ray lightcurves of the black hole candidate Cygnus X-1 by linear and nonlinear time series analysis methods. While a linear model describes the overall second order properties of the observed data well, surrogate data analysis reveals a significant deviation from linearity. We discuss the relation between shot noise models usually applied to analyze these data and linear stochastic autoregressive models. We debate statistical and interpretational issues of surrogate data testing for the present context. Finally, we suggest a combination of tools from linear and nonlinear time series analysis methods as a procedure to test the predictions of astrophysical models on observed data.

Journal Article↗