PubMed Health⌕ Search

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 163 records · Page 9Linked to original sources

Heart rate variability and 24-hour minimum heart rate.

Heart rate variability (HRV) indices based on 24-hr electrocardiograph recordings have been used in clinical research studies to assess the aggregate activity of the autonomic nervous system. Although 24-hr HRV is generally considered noninvasive, use in research protocols typically involves considerable data collection and processing expenses and substantial participant burden. The purposes of this research methods evaluation were to describe the relationships between 24-hr minimum heart rate (HR) and several 24-hr time domain HRV indices (Ln SDNN, Ln SDANN, Ln SDNNIDX, Ln RMSSD, and Logit50) across several research data sets (normal women, normal men, children enrolled in a study of recurrent abdominal pain, women with irritable bowel syndrome, sudden cardiac arrest survivors, and heart failure patients) and to explore the possibility that 24-hr minimum HR might serve as a simpler alternative or adjunct to HRV measures in some situations. The correlations of global HRV measures (e.g., Ln SDNN, Ln SDANN) with 24-hr minimum HR were consistently larger (typical r approximately -.80) than with average HR (typical r approximately -.50). In repeated measurements, change in minimum HR was also correlated with change in general HRV (typical r approximately -.60). However, modest differentiation of minimum HR and HRV measures was noted in patients taking certain classes of cardiac medications (e.g., anti-arrhythmics, beta blockers). Twenty-four-hour minimum HR is correlated with general time domain HRV measures and might be useful as a simpler proxy, surrogate, or auxiliary variable in some clinical research applications, especially those in which participants are not receiving cardiac medications.

Abdominal Pain↗

Heart rate variability: a measure of cardiac autonomic tone.

Analysis of HRV based on routine 24-hour Holter recordings provides a sensitive, noninvasive measurement of autonomic input to the heart. HRV can be measured in the time or frequency domain. Each frequency domain variable correlates at least r = 0.85 with a time domain variable. Thus time domain measures can be used as surrogates for frequency domain measures which may simplify future studies. Abnormalities of autonomic input to the heart, which are indicated by decreased indices of HRV, are associated with increased susceptibility to ventricular arrhythmias. Decreased indices of HRV are also associated with CHF, diabetes, and alcoholic cardiomyopathy. Decreased indices of HRV are an independent risk factor for mortality post MI and in patients with advanced CHF. Medications can also affect HRV, and that effect may become an important clinical consideration, especially in high-risk patients.

Autonomic Nervous System↗

[Atherogenic index of plasma is associated with carotid intima-media thickness in patients with type 2 diabetes mellitus].

OBJECTIVE: To investigate the relationship of atherogenic index of plasma (AIP), an indirect indicator of LDL particle size, to carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus (T2DM) among Chinese Han nationality population. METHODS: One hundred and seventy-nine type 2 diabetic patients and 87 healthy subjects from a population of Chinese Han nationality were included. The AIP is the logarithmically transformed ratio of TG/HDL-c, which may serve as a surrogate method for assessing LDL particle size. The carotid IMT, as a surrogate continuous variable for macroangiopathy, was measured by B-mode ultrasonography in type 2 diabetic patients. The patients with T2DM were divided into three subgroups according to the IMT: IMT < or = 0.65 mm, 0.65 mm < IMT < or = 1.1 mm and IMT > 1.1 mm. The Student-t test, one-way analysis of variance, univariate and multivariate analyses were implemented. RESULTS: (1) In T2DM group the values of triglyeeride (TG) and AIP were significantly higher than those in control group respectively, and the HDL-c value of T2DM group was significantly lower than that of control group. (2) There was significant difference in the age, body mass index (BMI), waist-hip ratio (WHR), the duration of DM, triglyceride (TG), total cholesterol (TC), LDL-c, HDL-c, HbAlc, TG/HDL-c and AIP among the three subgroups; the HDL-c value was inversely related to the IMT of T2DM, and all the other risk factors were positively related to the IMT of T2DM. (3) Multivariate analysis by linear regression showed that the value of AIP was an important risk factor in the pathogenesis and progress of IMT in patients with T2DM. CONCLUSION: AIP value, an indirect indicator of LDL particle size, is an important risk factor in pathogenesis and progress of IMT in patients with T2DM.

Adult↗

Salusin beta is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1.

The mas-like G protein-coupled receptors form a subfamily of G protein-coupled receptors that includes variable member numbers across different species and that have been shown to bind a wide variety of ligands from peptides to amino acid derivatives. While screening a library of peptides against different orphan G protein-coupled receptors, we found that human salusin beta activates the mouse mas-like G protein-coupled receptor, mMrgA1 with an EC(50) of about 300 nM. Salusin beta is a bioactive peptide recently discovered through bioinformatics analysis which stimulates arginine-vasopressin release from rat pituitary and causes rapid and profound hypotension and bradycardia. However, when we further analyzed the generality of the mMrgA1 activation, we found that human salusin beta does not activate corresponding human mas-like G protein-coupled receptors. Our results show that human salusin beta is a surrogate ligand of the mouse MrgA1 and raises a cautionary flag for experiments that analyze the pharmacological profiles of mas-like G protein-coupled receptors from different species.

Adenosine Triphosphatases↗

Estimating Lyapunov exponents in biomedical time series.

Among nonlinear dynamical invariants, determination of the largest Lyapunov exponent is well suited to positive identification of chaos in observed time series. When analyzing the dynamics of biomedical series, such as an electro-encephalogram (EEG), model-based methods should be used. Moreover, in the absence of any well founded theoretical model, and because of unexplained variability in the data, candidate models must provide for a stochastic component. Here we use nonlinear autoregressive stochastic modeling to estimate the dominant Lyapunov exponent in an EEG series and compute confidence intervals from surrogate data. The results are found to differ from those of approaches which aim at deleting noise prior to analysis.

Algorithms↗

Length of storage of transfused red cells and postoperative morbidity in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: The transfusion of old red cells (RBCs) may be associated with reduced delivery of oxygen to tissues and an increased risk of transfusion complications. The association of postoperative morbidity with the length of storage of perioperatively transfused RBCs was studied in 268 consecutive patients receiving a blood transfusion for coronary artery bypass graft surgery. STUDY DESIGN AND METHODS: The postoperative length of hospitalization, the postoperative length of stay in the intensive care unit, and the length of endotracheal intubation after the day of the operation were used as surrogate measures of global postoperative morbidity. The length of storage of the oldest transfused RBC unit, the mean length of storage of the oldest and second oldest RBC units, and the mean length of storage of all RBC units transfused to each patient were tested for association with the three outcome variables. Multiple linear regression analysis and Cox proportional-hazard analysis were used to adjust for the effects of confounding factors that pertained to each patient's severity of illness and the difficulty of each operation. RESULTS: There were no significant associations after adjustment for the effects of confounding factors. CONCLUSION: This study did not corroborate the previously reported association between transfusion of old RBCs and increased morbidity. However, there is surprisingly little research on the clinical outcomes of the transfusions of old RBCs, and this hypothesis should be investigated further.

Blood Preservation↗

Evaluation and documentation of rheumatoid arthritis disease status in the clinic: which variables best predict change in therapy.

To determine in clinical practice which rheumatoid arthritis (RA) clinical status variables are most associated with a change in disease modifying antirheumatic drug (DMARD) therapy, we studied 26,240 observations from 1905 RA patients occurring over 25 years. Variables included tender joint count, erythrocyte sedimentation rate (ESR), grip strength, visual analog scale for pain, global severity, fatigue and sleep, Health Assessment Question functional disability scale (HAQ), anxiety, depression and morning stiffness. Only the tender joint count required a physician. Observations at which a change in DMARD therapy occurred were compared to those where a change did not occur using generalized estimating equations (GEE) and classification and regression tree analysis (CART). Tender joint count, pain, global severity, and ESR were the 4 variables most strongly predictive of DMARD change. CART modeling indicated a special role for fatigue and sleep disturbance in some patients. These data add support in clinical practice for the ACR core set and the DAS set of variables. In addition, they validate the use of these variables in a practice setting. We suggest a minimum set of evaluations comprising: joint count, ESR or CRP, measures of pain and/or severity, a fatigue scale (fatigue being a surrogate for sleep disturbance), and a measure of function such as the HAQ or modified HAQ. Because only joint count requires physician participation, these evaluations are practical for the clinic, and allow quantitative measurement of RA status. With the use of quantile charts, the comparative status of RA and the change in RA status can be determined easily.

Adult↗

Ambient gas concentrations and personal particulate matter exposures: implications for studying the health effects of particles.

BACKGROUND: Data from a previous study conducted in Baltimore, MD, showed that ambient fine particulate matter less than 2.5 mum in diameter (PM2.5) concentrations were strongly correlated with corresponding personal PM2.5 exposures, whereas ambient O3, NO2, and SO2 concentrations were weakly correlated with their personal exposures to these gases. In contrast, many of the ambient gas concentrations were reasonable surrogates of personal PM2.5 exposures. METHODS: Personal multipollutant exposures and corresponding ambient air pollution concentrations were measured for 43 subjects living in Boston, MA. The cohort consisted of 20 healthy senior citizens and 23 schoolchildren. Simultaneous 24-hour integrated PM2.5, O3, NO2, and SO2 personal exposures and ambient concentrations were measured. All PM2.5 samples were also analyzed for SO4 (sulfate). We analyzed personal exposure and ambient concentration data using correlation and mixed model regression analyses to examine relationships among (1) ambient PM2.5 concentrations and corresponding ambient gas concentrations; (2) ambient PM2.5 and gas concentrations and their respective personal exposures; (3) ambient gas concentrations and corresponding personal PM2.5 exposures; and (4) personal PM2.5 exposures and corresponding personal gas exposures. RESULTS: We found substantial correlations between ambient PM2.5 concentrations and corresponding personal exposures over the course of time. Additionally, our results support the earlier finding that summertime gaseous pollutant concentrations may be better surrogates of personal PM2.5 exposures (especially personal exposures to PM2.5 of ambient origin) than they are surrogates of personal exposures to the gases themselves. CONCLUSIONS: Particle health effects studies that include both ambient PM2.5 and gaseous concentrations as independent variables must be analyzed carefully and interpreted cautiously, since both parameters may be serving as surrogates for PM2.5 exposures.

Aged↗

Testicular function of rats following exposure to microwave radiation.

Male Sprague-Dawley rats were exposed for 6 h per day for nine days to pulse-modulated microwave radiation (1.3 GHz, at 1-microseconds pulse width, 600 pulses per second). Exposures were carried out in cylindrical waveguide sections at a mean dose rate of 6.3 mW/g; sham controls were treated similarly and received no irradiation. At time periods corresponding to 0.5, 1.0, 2.0, and 4.0 cycles of the seminiferous epithelium, groups of four sham-irradiated and four irradiated rats were killed and the testes removed for analysis. Net mass of the testes, epididymides, and seminal vesicles; daily sperm production (DSP) per testis and per gram of testis; sperm morphology; and the number of epididymal sperm were determined. There were no statistically significant differences between the sham-irradiated and irradiated groups with respect to any measured variable. In a group of seven surrogate animals of similar body mass, the dose rate of 6.3 mW/g caused a net change in body temperature (via rectal probe) of 1.5 degrees C.

Animals↗

Hypoxanthine-guanine phosphoribosyltransferase reporter gene mutation for analysis of in vivo clonal amplification in patients with HTLV type 1-associated Myelopathy/Tropical spastic paraparesis.

We tested a surrogate selection approach utilizing mutation at a reporter gene [hypoxanthine-guanine phosphoribosyltransferase (hprt)] as a probe for in vivo cell division, for detection of clonal T cell expansion in human T lymphotropic (HTLV-1) carriers. Peripheral blood samples from HTLV-1-infected individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were tested to determine the hprt mutant frequency (Mf). Wild-type and hprt mutant T cell clones were isolated, and clonal identity determined by multiplex PCR and DNA sequencing of T cell receptor (TCR) variable region beta-chain (TCR BV) and third complementarity determining regions (CDR3). Seven samples from HAM/TSP patients were tested, and Mfs were within the normal range for adults (mean 11.3 x 10(-6), max 22.4 x 10(-6), min 5.6 x 10(-6)). The frequency of HTLV-1 infection in wild-type and hprt mutant T cells from HAM/TSP patients was determined to identify enrichment in the mutant fraction of cells. This analysis was performed on 196 isolates from 6 individuals with HAM/TSP. In each case, there is enrichment for virally infected cells in the hprt mutant fraction of isolates. Ten mutant and eight wild-type isolates from sample LS42A (Mf 8.4 x 10(-6)) were tested for clonality by TCR BV PCR and sequencing. Of the 10 hprt mutants, there were two in vivo-expanded clones (four isolates with two identical TCRs, or 80% unique TCR sequences). These studies may provide new insights into the precise mechanism of HTLV-1 leukemogenesis, and aid in the study of mutator phenotypes generated by a combination of Tax-mediated in vivo expansion and mutagenesis.

Clone Cells↗

The effects of the new 65 mile-per-hour speed limit on rural highway fatalities: a state-by-state analysis.

This paper examines the effects of the new 65 mile-per-hour (mph) speed limit on U.S. rural highway fatality counts. Separate analyses are conducted for each of the 40 states that had adopted the new (higher) limit by mid-1988. Using monthly Fatal Accident Reporting System (FARS) data from January 1976 through November 1988, time-series regression equations--including policy variables, seasonal variables, and surrogate exposure variables--are estimated for each state. The results suggest that the new laws have increased fatalities on both rural interstate and rural noninterstate highways in most states, but also that these effects differ substantially across the states. For rural interstate fatalities the estimates suggest a median (among the 40 states) effect of the increased speed limit of roughly 15% more fatalities; the median estimates for rural noninterstates suggest a 5% increase in fatalities due to the increased speed limits. Estimates such as those reported here should be revised as more information becomes available.

Accidents, Traffic↗

Determinants of lung cancer risk among cadmium-exposed workers.

Workers at a cadmium recovery plant in Globe, Colorado, showed an increased risk of lung cancer, which some investigators have attributed to cadmium exposure. We conducted a cohort mortality analysis of this work force and a case-control analysis of the lung cancer cases within this work force in order to assess the probable causes of the lung cancer excess. The Globe plant began as a lead smelter about 1886, switched to arsenic production in 1920, and became a cadmium metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are three potential lung carcinogens found in this workplace. Industrial hygiene data collected from 1943 onward served as the basis for the National Institute for Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned cadmium exposure estimates to employees based on their work area in the plant and calendar time. Few exposure data existed for substances other than cadmium. Feedstock ore concentrations were used as a surrogate measure of air arsenic levels. The arsenic content of the fines used as feedstock prior to 1940 was considerably higher than that of the fines used after 1940. Smoking histories had been obtained previously for 45% of the workers. A case-control analysis of the 25 cases of lung cancer known to have occurred among these workers through 1982 was conducted using three controls per case, matched by closest data of hire and age at hire. Potential causal agents for lung cancer included cadmium exposure, cigarette smoking, and arsenic exposure. Exposure variables for each case and control included estimated cumulative cadmium exposure in milligram-years per cubic meter, cigarette smoking history, and plant arsenic exposure status at the time of hire. Estimated cumulative cadmium exposures of cases and controls did not differ overall or within the date-of-hire strata. Cases were more than eight times more likely to have been cigarette smokers than were controls. Lung cancer risk in this workplace was more closely related to the period of hire, not to the cumulative cadmium exposure. The period of hire appears to be a surrogate for arsenic exposure as related to feedstock. The measures used here seem to indicate that exposure to arsenic and cigarette particulates, rather than to cadmium particulates, may have caused the increased rate of lung cancer of these workers.

Adult↗

Multivariate head injury threshold measures for various sized children seated behind vehicle seats in rear impacts.

Government recommendations to place children into the rear areas of motor vehicles to avoid airbag induced injuries have been complicated by the fact that most adult occupied front seats will collapse into the rear area during rear-impacts, and thus pose another potentially serious injury hazard to rear-seated children. Many variables affect whether or not a front seat occupant will collapse into the rear child, and whether that interaction could be injurious to the child. For instance, the severity of rear impact, coupled with front and rear occupant sizes (mass and stature), and the level of front seat strength, all interrelate to influence whether or not a rear seated child is likely to be impacted and possibly injured. The most common types of child injuries in these instances are head and chest injuries. In this study, a "high-low" experimental method was employed with a multi-level "factorial analysis" technique to study "multivariate" biomechanics of child head injury potential determined from rear-seated 3 and 6 year-old child surrogates in different types of vehicle bodies mounted to a sled system. The sled-buck systems were towed rearward into crushable barriers that matched the crash pulses of the vehicle types being tested. Various sizes of adult surrogates (i.e. 50 kg up to 110 kg), seated in both the "typical" low strength "single recliner" collapsing type front seat (i.e. 3.2 kN) and a much stronger "belt-integrated" seat design (i.e. up to 14.5 kN), were tested in the two different "sled body-buck" set-ups at various impact levels (i.e. 22.5 to 50 kph). One set-up used a popular minivan vehicle body with "built-in booster" seats for the 3 year-old. The other used a 4-door family sedan vehicle body with the 6 year-old in a standard rear bench seat. The parameters of the tests enabled the experimental data to be combined into polynomial "head injury" functions of the independent variables so the "likelihood" of rear child head-injury potential could be "mapped" over ranges of the key parameters. Accident cases were compared with predictions to verify the methodology.

Accidents, Traffic↗

Routine analysis of IgVH mutational status in CLL patients using BIOMED-2 standardized primers and protocols.

Current methods for the detection of IgVH mutational status in chronic lymphocytic leukemia (CLL), which identifies 2 subgroups of patients with significantly different outcomes, are laborious, expensive and do not lend themselves to a routine diagnostic setting. With the introduction of BIOMED-2 primers, a rapid protocol is now available. This study evaluated the protocol by examining DNA from 100 CLL patients. Conventional methods using RNA, and fluorescence in-situ hybridization (FISH) analysis for recurring chromosomal abnormalities, were carried out on 30 and 60 of these patients, respectively. There was complete concordance between the BIOMED-2 protocol and the RNA based method, both in mutational status and gene usage, whilst unmutated IgVH genes showed association with 17p13 and 11q23 deletions, and trisomy 12, associated with poor and intermediate outcomes, respectively. This study demonstrates that it is feasible to use the BIOMED-2 protocol in the diagnostic profile of CLL patients, obviating the need for inclusion of surrogate markers such as ZAP-70.

Adult↗

Estimated cerebral respiratory quotient and arteriovenous differences of CO2 in the ultra early detection of global ischemia in severe head injury.

The specificity of jugular bulb saturation (SjO2) and arteriovenous oxygen difference (AVDO2) to detect global cerebral ischemia remains controversial. An absolute increase in the arteriovenous difference of carbon dioxide tension (AVDpCO2) and, more specifically, the estimated respiratory quotient (eRQ = AVDpCO2/AVDO2) may indicate anaerobic CO2 production. We compared these variables with SjO2 to predict global cerebral ischemia. We selected 36 patients from a cohort of 69 consecutive patients suffering from severe traumatic brain injury. All patients had jugular bulb sampling within 6 hours after injury. Brain death at 48 hours was used as a surrogate index of irreversible ischemia to build a receiver operating characteristics (ROC) curve analysis. The mean (+/- standard deviation) eRQ in the 13 patients who died early (3.7 +/- 3.2 mmHg/ml/dl) was higher than the survivors (1.78 +/- 0.45 mmHg/ml/dl, P = 0.03). There was no differences in SjO2 between groups. The area under the ROC curves for eRQ, but not that of AVDpCO2, was greater (P = 0.04) than that of SjO2. The eRQ, more than AVDpCO2, appears to be a potentially more informative index of global cerebral ischemia than SjO2.

Adult↗

Sampling strategies in nested case-control studies.

A stratified version of nested case-control sampling which we call "countermatching" is presented. This design uses data available for all cohort members to obtain a sample for collecting additional information in a case-control substudy. Hitherto the only stratified sampling design for such studies has involved matching of controls to cases with respect to confounding variables. However, in some situations, rather than sampling to make controls as similar as possible to cases, we might wish to make them as different as possible. This is achieved by the counter-matched design. Statistical analysis of counter-matched studies is straightforward using existing computer software. We investigate the use of the design when a surrogate measure of exposure is available for the full cohort, but accurate exposure data is to be collected only in a nested case-control study, and when exposure data are available for the whole cohort but data concerning important confounders are not. Asymptotic relative efficiency calculations indicate that a substantial efficiency gain relative to simple random sampling of controls can be expected in these situations. We also illustrate how the design might be implemented in practice.

Bias↗

Correlation dimension maps of EEG from epileptic absences.

PURPOSE: The understanding of brain activity, and in particular events such as epileptic seizures, lies on the characterisation of the dynamics of the neural networks. The theory of non-linear dynamics provides signal analysis techniques which may give new information on the behaviour of such networks. METHODS: We calculated correlation dimension maps for 19-channel EEG data from 3 patients with a total of 7 absence seizures. The signals were analysed before, during and after the seizures. Phase randomised surrogate data was used to test chaos. RESULTS: In the seizures of two patients we could distinguish two dynamical regions on the cerebral cortex, one that seemed to exhibit chaos whereas the other seemed to exhibit noise. The pattern shown is essentially the same for seizures triggered by hyperventilation, but differ for seizures triggered by light flashes. The chaotic dynamics that one seems to observe is determined by a small number of variables and has low complexity. On the other hand, in the seizures of another patient no chaotic region was found. Before and during the seizures no chaos was found either, in all cases. CONCLUSIONS: The application of non-linear signal analysis revealed the existence of differences in the spatial dynamics associated to absence seizures. This may contribute to the understanding of those seizures and be of assistance in clinical diagnosis.

Adolescent↗

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization.

AIMS: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.

Aged↗