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Risk stratification in the asymptomatic child with Wolff-Parkinson-White syndrome.

PURPOSE OF REVIEW: As the safety and efficacy of invasive electrophysiologic studies and ablation therapy in pediatrics improves, there has been a greater interest in developing adequate risk stratification criteria for the asymptomatic pediatric patient with Wolff-Parkinson-White syndrome. This review will discuss the recent literature regarding this debate. RECENT FINDINGS: Recent retrospective and prospective studies of Wolff-Parkinson-White syndrome in asymptomatic pediatric patients have shown that the well established adult criteria for risk stratification may not be applicable in children. Both symptomatic and asymptomatic children had similar accessory pathway effective refractory periods and supraventricular tachycardia inducibility in recent invasive electrophysiologic studies. The first attempt at prospective evaluation of the use of ablation therapy in asymptomatic adult and pediatric patients with the condition has sparked a debate as to the definition of a high-risk patient and the utility of ablation in the asymptomatic patient. SUMMARY: It is still controversial whether the established criteria for risk stratification in adults can be confidently applied to the pediatric patient. The majority of pediatric electrophysiologists use invasive electrophysiologic studies for risk stratification and selection of appropriate therapy. This clinical practice reflects the increasing prevalence and safety of electrophysiologic study and ablation. Further studies to better define indications for study and ablation are still necessary, however, to define accurate criteria for risk stratification in this difficult pediatric problem.

Age Factors↗

Evaluating bias due to population stratification in epidemiologic studies of gene-gene or gene-environment interactions.

Confounding by ethnicity (i.e. population stratification) can result in bias and incorrect inferences in genotype-disease association studies, but the effect of population stratification in gene-gene or gene-environment interaction studies has not been addressed. We used logistic regression models to fit multiplicative interactions between two dichotomous variables that represented genetic and/or environmental factors for a binary disease outcome in a hypothetical cohort of multiple ethnicities. Biases in main effects and interactions due to population stratification were evaluated by comparing regression coefficients in mis-specified models that ignored ethnicities with their counterparts in models that accounted for ethnicities. We showed that biases in main effects and interactions were constrained by the differences in disease risks across the ethnicities. Therefore, large biases due to population stratification are not possible when baseline disease risk differences among ethnicities are small or moderate. Numerical examples of biases in genotype-genotype and/or genotype-environment interactions suggested that biases due to population stratification for main effects were generally small but could become large for studies of interactions, particularly when strong linkage disequilibrium between genes or large correlations between genetic and environmental factors existed. However, when linkage disequilibrium among genes or correlations among genes and environments were small, biases to main effects or interaction odds ratios were small to nonexistent.

Bias↗

The relationship between social stratification and all-cause mortality among children in the United States: 1968-1992.

BACKGROUND: US childhood poverty rates have increased for most of the past 2 decades. Although overall mortality among children has apparently fallen during this interval, these aggregate mortality rates may hide a disproportionate burden imposed on the least advantaged. This study assessed the impact of social stratification on long-term US childhood mortality rates and examined the temporal relationship between mortality attributable to social stratification and childhood poverty rates. METHODS: Using US childhood mortality data obtained from the Compressed Mortality File (National Center for Health Statistics) and a county-level measure of social stratification (residential telephone availability), I evaluated the impact of social stratification on long-term trends (1968-1992) in age-adjusted mortality and compared the resulting attributable proportions to trends in childhood poverty rates. RESULTS: Between 1968 and 1987 the proportion of US childhood deaths attributable to social stratification decreased from.22 to.17. Subsequently, it increased to.24 in 1992, despite continuous declines in overall childhood mortality rates. These proportions correlated strongly with earlier childhood poverty rates, taking into account an apparent 9-year lag. Among black children comparable trends were not observed, although throughout this time period their mortality rates were far higher than among the rest of the population and declined more slowly. CONCLUSIONS: Despite declining childhood mortality rates between 1968 and 1992, children living in the least advantaged counties continued to die at higher rates than those living in the most advantaged counties. This differential worsened considerably after 1987, and by 1992 had a substantive impact on US life expectancy at birth, resulting in perhaps the most significant (in terms of years of life lost) reversal in the health of the US public in the 20th century.

Adolescent↗

[Method for measurement of optical stratification porosity (OSP) and its application in studies of management for secondary forests].

Secondary forest is the main body of forests in China, and hence, its management plays a very important role in the projects of natural forest conservation and ecological environment construction in this country. The structure, especially the vertical stratification structure of secondary forest is one of the key factors in the management of secondary forest, and can be considered as the base of its management. Based on previous studies, the concept of stratification porosity was introduced, and the optical stratification porosity (OSP), which is the two dimensional alternative measurement of stratification porosity, could be used to represent the vertical stratification structure of secondary forest. The method using hemispherical photographic silhouette (photographic silhouette taken with fisheye lens) to estimate the OSP of a forest stand was also introduced. In addition, the possible applications of OSP in studies on the structure and restoration ecology of secondary forest, and the theory and techniques for the management of secondary forest were also given in this paper.

Conservation of Natural Resources↗

Assessing the validity of cardiac surgery risk stratification systems for CABG patients in a single center.

BACKGROUND: Most cardiac surgery risk stratification systems were primarily designed using patient-related factors to predict mortality and postoperative morbidity. Relative mortality rates are higher at cardiac surgery centers which perform surgery on elderly patients. Our aim was to assess the validity of risk stratification systems for our regional population. MATERIAL/METHODS: The study involved 1021 patients. Risk stratification was carried out using the EuroSCORE, Ontario, and QMMI scoring systems. Analysis comparing the scoring systems included sensitivity, specificity, predictive values, and receiver operating characteristics (ROC) curves. Accuracy was assessed using the systems' ability to avoid Type I and Type II errors. RESULTS: Sensitivity and specificity of the QMMI scoring system were 33.3% and 97.2%, of EuroSCORE 20.7% and 96.7%, and of Ontario 21.1% and 94.4%, respectively. The best positive predictive value was for QMMI and EuroSCORE with 75% versus Ontario's 50%. The highest negative predictive value was QMMI's 85.4% versus Ontario's 78.9% and EuroSCORE's 72.0%. The best accuracy showed QMMI scoring with 84.5% versus Ontario's 78.9% and EuroSCORE's 72.2%. CONCLUSIONS: All the investigated risk stratification systems were moderately predictive. The QMMI score showed the best predictive characteristics (sensitivity, specificity, and accuracy) for our patient population. The QMMI system had high specificity and accuracy. The EuroSCORE system showed mortality overprediction for our population, associated with high false negative test results and low accuracy. The Ontario risk stratification system often commits Type II errors, associated with a high rate of false positive test results and low accuracy.

Age Factors↗

Development and regulation of dendritic stratification in retinal ganglion cells by glutamate-mediated afferent activity.

In the mature retina, the dendrites of retinal ganglion cells (RGCs) are segregated into either ON or OFF sublaminae of the inner plexiform layer (IPL), but early in development the dendritic processes of these cells are multistratified, ramifying throughout the IPL. We examined the time course of dendritic stratification in developing beta cells, the largest class of ganglion cells in the cat retina, by retrograde labeling of fixed tissue with Dil. Dendritic stratification begins in the central and peripheral retina by embryonic day 50, about 2 weeks before birth and is not fully completed until 5 months postnatally. A clear central-to-peripheral gradient in the incidence of stratified beta cells first becomes evident shortly after birth. This stratification process was effectively halted by short-term intraocular injections (4-11 d) of the glutamate analog 2-amino-4-phosphonobutyrate (APB), which hyperpolarizes rod bipolar cells and ON cone bipolar cells, thereby preventing the release of glutamate by these interneurons. APB treatment did not alter the somal sizes or the tangential extent of the dendrites of developing beta cells, nor did it cause abnormal loss of these neurons. The organization of the inner nuclear layer, containing the APB-sensitive bipolar cells, was also not compromised by such injections. When APB treatment was discontinued there was a rapid resumption of dendritic stratification resulting in a normal incidence of stratified RGCs. Thus, short-term APB treatment causes a delay rather than a permanent arrest of the stratification process.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis.

CONTEXT: Estimation of mortality risk in patients hospitalized with acute decompensated heart failure (ADHF) may help clinicians guide care. OBJECTIVE: To develop a practical user-friendly bedside tool for risk stratification for patients hospitalized with ADHF. DESIGN, SETTING, AND PATIENTS: The Acute Decompensated Heart Failure National Registry (ADHERE) of patients hospitalized with a primary diagnosis of ADHF in 263 hospitals in the United States was queried with analysis of patient data to develop a risk stratification model. The first 33,046 hospitalizations (derivation cohort; October 2001-February 2003) were analyzed to develop the model and then the validity of the model was prospectively tested using data from 32,229 subsequent hospitalizations (validation cohort; March-July 2003). Patients had a mean age of 72.5 years and 52% were female. MAIN OUTCOME MEASURE: Variables predicting mortality in ADHF. RESULTS: When the derivation and validation cohorts are combined, 37,772 (58%) of 65,275 patient-records had coronary artery disease. Of a combined cohort consisting of 52,164 patient-records, 23,910 (46%) had preserved left ventricular systolic function. In-hospital mortality was similar in the derivation (4.2%) and validation (4.0%) cohorts. Recursive partitioning of the derivation cohort for 39 variables indicated that the best single predictor for mortality was high admission levels of blood urea nitrogen (> or =43 mg/dL [15.35 mmol/L]) followed by low admission systolic blood pressure (<115 mm Hg) and then by high levels of serum creatinine (> or =2.75 mg/dL [243.1 micromol/L]). A simple risk tree identified patient groups with mortality ranging from 2.1% to 21.9%. The odds ratio for mortality between patients identified as high and low risk was 12.9 (95% confidence interval, 10.4-15.9) and similar results were seen when this risk stratification was applied prospectively to the validation cohort. CONCLUSIONS: These results suggest that ADHF patients at low, intermediate, and high risk for in-hospital mortality can be easily identified using vital sign and laboratory data obtained on hospital admission. The ADHERE risk tree provides clinicians with a validated, practical bedside tool for mortality risk stratification.

Acute Disease↗

Modulation of corneal epithelial stratification by polymer surface topography.

The topography and porosity of a polymer may affect the epithelialization of a corneal implant. We used an in vitro model to examine the effect of polymer surface topography on corneal epithelial tissue stratification and the deposition of proteins associated with epithelial adhesion. A range of topographies was provided by polycarbonate membranes with nominal pore diameters of 0.1, 0.4, 0.8, 1.0, 2.0, or 3.0 microm and a nonporous surface. Stratification of epithelial tissue outgrowth on these surfaces was evaluated using light and electron microscopy. Deposition of proteins associated with basement membrane and adhesion complex formation at the tissue-polymer interface was assessed using immunohistochemistry. Surfaces with pores in the 0.1-0.8-microm-diameter range supported superior stratification and protein deposition compared with those containing pores of > or = 1.0 microm. Cytoplasmic processes penetrated single pores 2.0 and 3.0 microm in diameter and fused pores 1.0 microm in diameter. Tissue on the nonporous surface had a lower level of stratification compared with surfaces with pores 0.1-0.8 microm in diameter. These results point to the significance of surface topography in biomaterial applications that require persistent epithelialization.

Animals↗

Detecting association in a case-control study while correcting for population stratification.

Case-control studies are subject to the problem of population stratification, which can occur in ethnically mixed populations and can lead to significant associations being detected at loci that have nothing to do with disease. Here, we describe a way to measure and correct for stratification by genotyping a moderate number of unlinked genetic markers in the same set of cases and controls in which a candidate association was found. The average of association statistics across the markers directly measures stratification. By dividing the candidate association statistic by this average, a P-value can be obtained that corrects for stratification.

Case-Control Studies↗

On the development of the stratification of the inner plexiform layer in the chick retina.

This study investigated the development of the subdivision of the chick inner plexiform layer (IPL). The approach included an immunohistological analysis of the temporal and spatial expressions of choline acetyltransferase, of the neural-glial-related and neural-glial cell adhesion molecules (NrCAM and NgCAM, respectively) and axonin-1, and of inwardly rectifying potassium (Kir) channels in 5- to 19-day-old (E5-E19) embryos. Ultrastructural investigations evaluated whether synaptogenesis accompanies the onset of differentiation of the IPL. We found that the differentiation of the IPL started at E9. Distinct cholinergic strata appeared, NrCAM immunoreactivity showed a poorly defined stratification, and Kir3.2 was expressed in the IPL and in the inner nuclear layer. From E10 until late E14, NgCAM- and axonin-1-immunoreactive strata emerged in an alternating sequence from the outer to the inner IPL. During this period, the NrCAM pattern sharpened, and eventually five bands of weaker and stronger immunoreactivity were found. Conventional synapses formed at the beginning of E9, and stratification of the IPL also began on the same day at the same location. Synaptogenesis and stratification followed a gradient from the central to the peripheral retina. The topographic course of differentiation of the IPL generally corresponded to the course of maturation of ganglion and amacrine cells. Synaptogenesis and the expression of G-protein-gated Kir3.2 channels accompanied the onset of stratification. These events coincide with the occurrence of robust and rhythmic spontaneous neuronal activity. The subsequent differentiation of the IPL seemed to be orchestrated by several mechanisms.

Animals↗

Golgi-impregnated amacrine cells and GABAergic retinal neurons: a comparison of dendritic, immunocytochemical and histochemical stratification in the inner plexiform layer of rat retina.

This paper concerns the banding pattern produced in the inner plexiform layer of rat retina by glutamic acid decarboxylase (GAD) immunocytochemistry. It presents a comparison of this pattern with the dendritic stratification of neurons that are reasonable candidates for GABAergic amacrine cells in Golgi preparations, and also with the banding patterns produced by other histochemical techniques. First, the spacing of five dense GAD-positive bands and four intervening less dense bands in central retina is quantitatively described. Second, examples of a particular, morphologically homogenous group of Golgi-impregnated amacrine cells are examined in the details of their structure, especially with regard to their dendritic stratification. Computer reconstructions of the dendritic trees of some of these narrow-field, multistratified amacrines are compared with the GAD-positive banding pattern. This group of amacrines is judged to represent many of the GABAergic neurons in rat retina, accounting for the form and distribution of GAD-positive synaptic terminals by their dendritic morphology and stratification. Third, a general schema for the laminar subdivision (stratification) of the inner plexiform layer in rat retina is derived from a comparison of the results of several histochemical procedures. Finally, similarities and differences in the distribution of GAD-positive amacrine cell dendrites are noted among mammals and the functional implications of their broad distribution are discussed. A conspicuous difference is cited between mammals and certain nonmammalian vertebrates in which GAD-positive dendrites are restricted to sublamina beta (ON-center cells) of the inner plexiform layer.

Animals↗

Joint modeling of genetic association and population stratification using latent class models.

We show how latent class log-linear models can be used to test for an association between a candidate gene and a disease phenotype in a stratified population when the stratification is unobserved. The stratification may arise because of several ethnic groups or immigration and may lead to spurious associations between several loci and the disease. The information about the stratification is drawn from additional markers that are chosen to be independent of the disease and unlinked to the candidate gene and to each other within each population stratum. We use the EM algorithm to simultaneously estimate all the model parameters, including proportions of individuals in the latent population strata. The latent class model is used to test the phenotype association of single nucleotide polymorphism markers in four candidate regions in population-based case-control data selected from simulated Genetic Analysis Workshop (GAW) 12 population isolate 30. The analysis clearly demonstrates how the number of false positive associations can be reduced when the model accounts for population stratification.

Case-Control Studies↗

Population stratification confounds genetic association studies among Latinos.

In the United States, asthma prevalence and mortality are the highest among Puerto Ricans and the lowest among Mexicans. Case-control association studies are a powerful strategy for identifying genes of modest effect in complex diseases. However, studies of complex disorders in admixed populations such as Latinos may be confounded by population stratification. We used ancestry informative markers (AIMs) to identify and correct for population stratification among Mexican and Puerto Rican subjects participating in case-control studies of asthma. Three hundred and sixty-two subjects with asthma (Mexican: 181, Puerto Rican: 181) and 359 ethnically matched controls (Mexican: 181, Puerto Rican: 178) were genotyped for 44 AIMs. We observed a greater than expected degree of association between pairs of AIMs on different chromosomes in Mexicans (P < 0.00001) and Puerto Ricans (P < 0.00002) providing evidence for population substructure and/or recent admixture. To assess the effect of population stratification on association studies of asthma, we measured differences in genetic background of cases and controls by comparing allele frequencies of the 44 AIMs. Among Puerto Ricans but not in Mexicans, we observed a significant overall difference in allele frequencies between cases and controls (P = 0.0002); of 44 AIMs tested, 8 (18%) were significantly associated with asthma. However, after adjustment for individual ancestry, only two of these markers remained significantly associated with the disease. Our findings suggest that empirical assessment of the effects of stratification is critical to appropriately interpret the results of case-control studies in admixed populations.

Alleles↗

Artificial neural network based model for cardiovascular risk stratification in hypertension.

This study was to develop an objective method to stratify cardiovascular risk in hypertension. Stratification for cardiovascular risk is crucial in deciding treatment strategy for hypertension but has yielded undesirable results in clinic due to its low accuracy which is caused by physicians' subjective experience and the uncertainty of patients' statements. Our model proposed herein overcomes these disadvantages by applying artificial neural network based on a classic back propagation net. The model input is derived from the clinical investigation. The target output is the stratification level of total cardiovascular risk, which is learned from the guidelines of hypertension treatment. Study in 348 normotensive and hypertensive subjects showed that the results of model stratification are consistent with the standard stratification suggested by hypertension guidelines in 81.61% cases. The results confirm the accuracy of the model and demonstrate its ability in risk evaluation for hypertension.

Algorithms↗

Risk stratification with electrocardiographic-gated dobutamine stress technetium-99m sestamibi single-photon emission tomographic imaging: value of heart rate response and assessment of left ventricular function.

OBJECTIVES: The purpose of this research was to evaluate the significance of heart rate response to dobutamine and the assessment of left ventricular (LV) function during risk stratification of patients undergoing dobutamine stress myocardial perfusion imaging (DSMPI). BACKGROUND: Dobutamine stress myocardial perfusion imaging has been shown to effectively risk stratify highly selected patients. However, based on perfusion alone, patients with normal and abnormal tests have twice the risk as comparable patients with exercise testing. The added value of assessment of LV function and the heart rate response to dobutamine in risk stratification of these patients is unknown. METHODS: Follow-up information (cardiac death or non-fatal myocardial infarction) was obtained on 1,367 consecutive patients who underwent DSMPI due to inability to perform adequate exercise and contraindications to vasodilators. Perfusion images were interpreted using a 17-segment model. Abnormal perfusion and function were defined as: summed stress score > or =4 and ejection fraction <50%, respectively. RESULTS: Annualized event rates (AERs) were related to the extent/severity of perfusion defects and worsening LV function. A three-risk category model was constructed from combined assessment of perfusion and function, with AERs of 2.4% (both normal), 5.8% (discordant), and 11.3% (both abnormal); p < 0.001. Stress electrocardiogram (ECG) data added incremental value to myocardial perfusion alone but not to combined assessment of perfusion and function. Importantly, inability to achieve 85% of mean predicted heart rate was associated with worse outcomes and was an independent predictor of cardiac events. For patients in whom perfusion, function, and stress ECG response were normal, inability to achieve target heart rate was associated with significantly higher AER (1.5% vs. 3.4%, respectively, p = 0.021). CONCLUSIONS: In highly selected patients undergoing DSMPI, assessment of perfusion and function is effective in risk stratification. The stress ECG and heart rate response to dobutamine have prognostic value and should be incorporated into image interpretation so as to maximize risk stratification.

Aged↗

Defining high risk prostate cancer--where do we set the bar? A translational science approach to risk stratification.

PURPOSE: Risk stratification is commonly used in patients with prostate cancer but this effort has had no demonstrable effect on patient decision making for initial therapy. We propose new risk strata for clinically localized prostate cancer. MATERIALS AND METHODS: We examined current stratification methods for prostate cancer and their impact on prostate cancer therapy. RESULTS: Three risk strata for patients with clinically localized prostate cancer are proposed. Stratum 1 includes patients in whom active surveillance is associated with a low risk of disease progression. Stratum 2 includes patients in whom monotherapy, including external beam, interstitial radiotherapy or radical prostatectomy, is generally successful. Stratum 3 includes patients at high risk for recurrence with monotherapy in whom multimodal therapy may be superior. CONCLUSIONS: Risk stratification systems for prostate cancer should harmonize the needs of researchers to develop comparable groupings of patients, of patients who seek guidance on optimal therapy and of clinical trialists who seek to advance therapy for this disease. Our new stratification system provides such a structure.

Decision Making↗

Stress myocardial perfusion imaging versus echocardiography for the diagnosis and risk stratification of patients with known or suspected coronary artery disease.

Stress perfusion imaging and stress echocardiography (ECHO) are both very useful for assessment of diagnosis and risk stratification of patients with coronary artery disease (CAD). Both techniques have been well validated during exercise and inotropic stress, but coronary vasodilation stress is better used in combination with perfusion imaging. The overall sensitivity for detection of CAD is slightly higher by single photon emission computed tomography (SPECT) than by two-dimensional (2D) ECHO during all stress modalities, whereas the specificity is slightly higher by ECHO, although the differences in general are not statistically significant. SPECT, however, appears to be superior to ECHO in the diagnosis of isolated circumflex stenosis, as well as for the correct identification of multivessel CAD. A substantially greater amount of information is available regarding risk stratification with SPECT than with 2D ECHO. Although the data suggest that both techniques are very useful for risk stratification of patients with stable CAD, after myocardial infarction, and for preoperative risk stratification, the risk for cardiac events is lower in the presence of a normal stress SPECT study than of a normal stress ECHO.

Coronary Disease↗

Various manifestations of stratification phenomenon during intravenous cholangiography.

The authors classify various types of stratification phenomenon during intravenous cholangiography. The stage of gallbladder opacification in the recumbent position has been classified as (I) mottled, (II) dendritic, (III) ring-like, and (IV) homogeneous. 'Dendritic' type of stratification phenomenon has never been reported in the literature to our knowledge. At 20 min following infusion of contrast material homogeneous opacification of the gallbladder was noticed in only 14% of patients. The others fell into types I, II or III of stratification phenomenon. In contrast, 87% of the opacified gallbladders were homogeneous on the after fatty meal film. It is therefore mandatory for diagnosis that either a 24 h film or a fatty meal film be taken to avoid the stratification phenomenon.

Cholangiography↗