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PubMed1997

Major benefit from antiplatelet therapy for patients at high risk for adverse cardiac events after coronary Palmaz-Schatz stent placement: analysis of a prospective risk stratification protocol in the Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial.

BACKGROUND: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial is a randomized study in which antiplatelet therapy is compared with anticoagulant therapy after coronary stent placement, showing a significantly lower rate of noncardiac and cardiac events with antiplatelet therapy. The present study is a report of the analysis of a prospective risk stratification protocol in the ISAR Trial and the association with the incidence of adverse cardiac events and stent vessel occlusion. METHODS AND RESULTS: In all 517 patients randomized in the ISAR Trial, risk stratification was done with a list of 18 clinical, procedural, and angiographic variables: 165 patients with two or fewer criteria were classified as low risk, 148 patients with three criteria were classified as intermediate risk, and 204 patients with four or more criteria were classified as high risk. Within a 30-day follow-up, cardiac event rate (death, myocardial infarction, repeat intervention) was 6.4% for high-risk, 3.4% for intermediate-risk, and 0% for low-risk patients (P<.01). Stent vessel occlusion occurred in 5.9%, 2.7%, and 0%, respectively (P<.01). There was no significant difference between anticoagulant and antiplatelet therapy in the low- and intermediate-risk groups. In high-risk patients, however, the cardiac event rate was 12.6% with anticoagulant therapy and 2.0% with antiplatelet therapy (P=.007), and the rate of stent vessel occlusion was 11.5% and 0%, respectively (P<.001). CONCLUSIONS: This risk stratification protocol can help to identify patients at risk for adverse cardiac events and stent vessel occlusion. Patients in the high-risk group had the most benefit from antiplatelet therapy. These data suggest that antiplatelet therapy is the therapy of choice after coronary stenting specifically for patients with acute ischemic syndromes, difficult procedures, or suboptimal final results.

Angioplasty, Balloon, Coronary↗

PubMed1988

Income under female versus male control: hypotheses from a theory of gender stratification and data from the Third World.

This article presents a summary of Blumberg's general theory of gender stratification, which emphasizes relative male/female control of economic resources as a main (although not sole) predictor of a broad array of gender stratification consequences. It also reviews evidence from numerous Third World countries that men and women spend income under their control differently--with women holding back less for themselves and spending more on child nutrition and family basic human needs. Thus the data indicate that when women lose control of income, what is affected is not only their relative marital/familial power (and self-esteem) but also family well-being. Moreover, evidence is presented that planned Third World development projects that rely on female labor but do not provide women with a return to that labor also are likely to suffer: women will attempt to reallocate their efforts to tasks yielding income under their own control. In Africa, where women raise most locally marketed/consumed food and usually have specific familial obligations that require them to have independently controlled income, the bypassing of women farmers and undercutting their returns may be an important--albeit unheralded--factor in the region's food crisis. In sum, the Third World data support both the theory of gender stratification and the relative resources approach to marital power, and point the way to broadening the US marital/family power debate to include male/female spending patterns.

Africa↗

PubMed2006

Using ancestry-informative markers to define populations and detect population stratification.

A serious problem with case-control studies is that population subdivision, recent admixture and sampling variance can lead to spurious associations between a phenotype and a marker locus, or indeed may mask true associations. This is also a concern in therapeutics since drug response may differ by ethnicity. Population stratification can occur if cases and controls have different frequencies of ethnic groups or in admixed populations, different fractions of ancestry, and when phenotypes of interest such as disease, drug response or drug metabolism, also differ between ethnic groups. Although most genetic variation is inter-individual, there is also significant inter-ethnic variation. The International HapMap Project has provided allele frequencies for approximately three million single nucleotide polymorphisms (SNPs) in Africans, Europeans and East Asians. SNP variation is greatest in Africans. Statistical methods for the detection and correction of population stratification, principally Structured Association and Genomic Control, have recently become freely available. These methods use marker loci spread throughout the genome that are unlinked to the candidate locus to estimate the ancestry of individuals within a sample, and to test for and adjust the ethnic matching of cases and controls. To date, few case-control association studies have incorporated testing for population stratification. This paper will focus on the debate about the quantity and methods for selection of highly informative marker loci required to characterize populations that vary in substructure or the degree of admixture, and will discuss how these theoretically desirable approaches can be effectively put into practice.

Case-Control Studies↗

PubMed2005

The quantitative trait linkage disequilibrium test: a more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification.

Linkage analysis based on identity-by-descent allele-sharing can be used to identify a chromosomal region harboring a quantitative trait locus (QTL), but lacks the resolution required for gene identification. Consequently, linkage disequilibrium (association) analysis is often employed for fine-mapping. Variance-components based combined linkage and association analysis for quantitative traits in sib pairs, in which association is modeled as a mean effect and linkage is modeled in the covariance structure has been extended to general pedigrees (quantitative transmission disequilibrium test, QTDT). The QTDT approach accommodates data not only from parents and siblings, but also from all available relatives. QTDT is also robust to population stratification. However, when population stratification is absent, it is possible to utilize even more information, namely the additional information contained in the founder genotypes. In this paper, we introduce a simple modification of the allelic transmission scoring method used in the QTDT that results in a more powerful test of linkage disequilibrium, but is only applicable in the absence of population stratification. This test, the quantitative trait linkage disequilibrium (QTLD) test, has been incorporated into a new procedure in the statistical genetics computer package SOLAR. We apply this procedure in a linkage/association analysis of an electrophysiological measurement previously shown to be related to alcoholism. We also demonstrate by simulation the increase in power obtained with the QTLD test, relative to the QTDT, when a true association exists between a marker and a QTL.

Genetic Predisposition to Disease↗

PubMed2006

Health inequality in adolescence. Does stratification occur by familial social background, family affluence, or personal social position?

BACKGROUND: Two new sets of stratification indicators--family's material affluence and adolescent's personal social position- were compared with traditional indicators of familial social position based on parental occupation and education for their ability to detect health inequality among adolescents. METHODS: Survey data were collected in the Adolescent Health and Lifestyle Survey in 2003 from nationally representative samples of 12-, 14- and 16-year-old Finns (number of respondents 5394, response rate 71%). Indicators of the familial social position were father's socio-economic status, parents' education, parents' labour market position. Indicators of material affluence were number of cars, vacation travels, and computers in the family, own room and amount of weekly spending money. Adolescent's personal social position was measured as school performance. Measures of health were long-standing illness, overweight, use of mental health services, poor self-rated health and number of weekly health complaints. Ordinal logistic regression analysis was applied to study the associations between stratification indicators and health variables. RESULTS: All three groups of indicators of social stratification showed inequality in health, but the strongest associations were observed with the adolescent's personal social position. Health inequality was only partly identifiable by the traditional indicators of familial social position. The direction of the inequality was as expected when using the traditional indicators or personal social position: adolescents from higher social positions were healthier than those from lower positions. The indicators of family's material affluence showed mainly weak or no association with health and some of the indicators were inversely associated, although weakly. CONCLUSION: In addition to traditional indicators describing the socio-structural influences on the distribution of health among adolescents, indicators of family's material affluence should be further developed. Adolescents' personal social position should be included in the studies of health inequalities.

Adolescent↗

PubMed2005

Performance of a population-based cardiac risk stratification tool in Asian patients with chest pain.

OBJECTIVES: Most contemporary cardiac risk stratification tools have been derived and validated in mixed-race populations. Their validity in single-race populations has not been tested. The authors sought to compare the performance of a risk stratification tool between a mixed-race U.S. patient population and an Asian patient population. METHODS: This study is an analysis of data from the Internet Tracking Registry for Acute Coronary Syndromes (i(*)trACS) registry of patients with chest pain presenting to the emergency departments of eight U.S. centers and one site in Singapore. The Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) was computed for included patients, and its performance in predicting acute coronary syndrome (ACS) was compared between patients from the United States and Singapore. RESULTS: Of the 11,991 included patients, 1,120 experienced ACS. Although the ACI-TIPI demonstrated similar accuracy among groups (area under the curve, 0.729 [U.S.] vs. 0.719 [Singapore]; p = 0.5611), sensitivity and specificity were different when equal ACI-TIPI thresholds were considered. Recreating the logistic regression models used to create the ACI-TIPI showed similar results between the derived parameters and the parameters estimated for the U.S. group. In contrast, age older than 50 years (log-odds ratio [LOR], 0.107; 95% confidence interval [CI] = 0.518 to 0.713), male gender (LOR, 0.487; 95% CI = 0.149 to 1.122), and chest pain as a primary complaint (LOR, 0.237; 95% CI = 0.139 to 0.613) had little predictive power in patients from Singapore. CONCLUSIONS: Differences exist in presentation and factors associated with ACS among patients from the United States and Singapore that may affect the performance of risk stratification tools. These findings suggest that cardiac clinical decision rules need international validation.

Acute Disease↗

PubMed1989

Onset of expression of peanut lectin-binding glycoproteins is correlated with stratification of keratinocytes during human epidermal development in vivo and in vitro.

During gestation the epidermis develops from a single layer of ectoderm into a layer of keratinocytes overlaid by a layer of periderm; this is followed by a progressive increase in the number of layers of keratinocytes, until finally the distinct granular and cornified layers characteristic of mature epidermis are formed. As part of our investigation into the function of the peanut lectin-binding glycoproteins of cultured human keratinocytes, we have examined their expression at different stages of human epidermal development. We found that the onset of expression of the glycoproteins coincided with the transition from a two- to a three-layered epidermis, both in vivo and in organ culture. In adult epidermis, the patterns of binding of peanut lectin and Limax flavus lectin are complementary, with peanut binding more strongly to suprabasal keratinocytes and Limax flavus lectin binding more strongly to cells in the basal layer. We found that the complementary pattern of binding of the two lectins was established at, or shortly after, the onset of stratification and retained throughout development. In contrast, expression by keratinocytes of involucrin, a protein precursor of the cornified envelope, occurred after stratification had begun. Finally, we identified the peanut lectin-binding glycoproteins of adult epidermis by immunoblotting with an antiserum raised against the glycoproteins of cultured neonatal keratinocytes. In conclusion, expression of the peanut lectin-binding glycoproteins is an early event in epidermal development, and this would be consistent with a role for the glycoproteins in stratification.

Embryonic and Fetal Development↗

PubMed2025

Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity and tested the value of these scores in predicting progression. Genome-wide association studies identified no loci associated with progression at genome-wide significance (α = 5×10-8); MR analyses provided no significant evidence of an association between cognitive decline in AD patients and protein levels in brain, cerebrospinal fluid (CSF), and plasma. Polygenic risk scores for AD risk did not reliably stratify fast from slow progressors; however, a deeper investigation found that APOE ε4 status predicts amyloid-β and tau positive versus negative patients (odds ratio for an additional APOE ε4 allele = 5.78 [95% confidence interval: 3.76-8.89], P<0.001) when restricting to a subset of patients with available CSF biomarker data. These results provided no evidence for large-effect, common-variant loci involved in the rate of memory decline, suggesting that patient stratification based on common genetic risk factors for progression may have limited utility. Where clinically relevant biomarkers suggest diagnostic heterogeneity, there is evidence that a priori identified genetic risk factors may have value in patient stratification. Mendelian randomization was less tractable due to the lack of large-effect loci, and future analyses with increased samples sizes are needed to replicate and validate our results.

Alzheimer Disease↗

PubMedDate not supplied

Germination responses to GA3 and stratification of threatened Festuca L. species from Eastern Mediterranean.

The seed germination characteristics of three threatened Festuca sp. [F. punctoria Sm., F. cyllenica Boiss. et Heldr. subsp. uluana Markgr.-Dannenb., F. paphlagonica (St.-Yves) Markgr.-Dannenb. subsp. paphlagonica] were investigated. These species are endemic and spread on alpine belt. The study was carried out with wet-cold and dry-cold stratification throughout 15 days, different doses of GA3 (50, 100 and 150 ppm) and hormone-stratification combined treatments, and non-treatment series. We found that the germination rates of three fescue seeds for various treatment series were different. The mean germination percentage of F. cyllenica was higher (80%) than that of F. punctoria and F. paphlagonica which were fairly low (50-60%). Germination rates increased by wet-stratification treatment in F. punctoria and also increased with 100 ppm GA3 application to the seeds of F. paphlagonica. When taken into consideration the germination percentages of all fescue species, the seeds of F. punctoria and F. paphlagonica can be dormant, but the seeds of F. cyllenica are non-dormant.

Festuca↗

PubMed1989

Geographical stratification by socio-economic status: methodology from a household survey with elderly people in S. Paulo, Brazil.

Considering that in most developing countries there are still no comprehensive lists of addresses for a given geographical area, there has always been a problem in drawing samples from the community, ensuring randomisation in the selection of the subjects. This article discusses the geographical stratification by socio-economic status used to draw a multistage random sample from a community-based elderly population living in a city like S. Paulo-Brazil. Particular attention is given to the fact that the proportion of elderly people in the total population of a certain area appeared to be a good discriminatory variable for such stratification. The validity of the stratification method is analysed in the light of the socio-economic results obtained in the survey.

Aged↗

PubMedDate not supplied

Stratification and oxidation-reduction potential change in an aerobic and sulfate-reducing biofilm studied using microelectrodes.

Recent studies in aerobic-nitrifying biofilms demonstrated the heterogeneity of biofilms used in wastewater treatment and led to modifications of the homogeneous assumptions in the conventional biofilm kinetic models. However, the stratification in aerobic-anaerobic biofilms has not been well investigated because of a lack of effective experimental tools. In this study a suite of microelectrodes, recently developed in the authors' laboratory, was used to examine the stratification of microbial processes and the change of oxidation-reduction potential (ORP) within an aerobic, sulfate-reducing biofilm. The microelectrodes have tip diameters of 3 to 20 microm and a high spatial resolution. They were used to measure the profiles of oxygen, total dissolved sulfide, ORP, and pH as a function of depth in the biofilm. The biofilm reactor was used to treat an azo-dye-containing wastewater with a chemical oxygen demand of 160 mg/L. The reactor bulk-phase dissolved oxygen concentration of the biofilm was 1.7 mg/L. The experimental results demonstrated that the microbial processes in the biofilm were stratified. In this biofilm, aerobic oxidation took place only in a shallow layer of 0.55 mm near the surface and sulfate reduction occurred in the deeper anoxic zone. The ORP changed with the shift of primary microbial process. The ORP was +362 mV at the biofilm surface and -166 mV near the substratum. Near the interface between the aerobic zone and the sulfate reduction zone, a surprisingly sharp decrease of ORP from a positive potential of +194 mV to a negative potential of -77 mV was observed. This occurred within a narrow band of 50 microm in depth. These new experimental findings support the concept of stratification of microbial processes and the associated ORP change in biofilms.

Azo Compounds↗

PubMed2003

A rosetta stone for coronary calcium risk stratification: agatston, volume, and mass scores in 11,490 individuals.

OBJECTIVE: We introduce stratification data for three methods (Agatston, volume, mass) obtained from one single patient population. MATERIALS AND METHODS: Measurements in 11,490 individuals scanned from 1999 to 2002 with electron-beam CT were used for this study. RESULTS: Our Agatston score ranges agree reasonably well with the Kondos values except for measurements in patients at the extreme ages, at which we sampled a wider age range and consequently had different biases of averages. Neither method is preferable because except for a small percentage of individuals near the dividing lines, stratification is the same for the three methods. When we matched them against a known "lesion" phantom, the Agatston and volume scores behave nonlinearly, and the latter grossly overestimates volume. The mass method is linear except for lesions near the edge of detectability and matches known volumes to within a small percentage. CONCLUSION: We provide validated risk stratification data for use with mass scoring methods.

Adult↗

PubMed2006

Medulloblastomas: new directions in risk stratification.

Medulloblastomas (MBs) are the most common malignant brain tumors in children. Current therapeutic approaches combine surgery, radiotherapy, and chemotherapy. Although, there has been significant improvement in long-term survival rates, the tumor remains incurable in about a third of patients while cognitive deficits and other sequelae of therapy are common among long-term survivors. Hence a major challenge remains to differentiate high-from low-risk patients and to tailor therapy based on the degree of biological aggressiveness. A clinical risk-stratification system has been widely used in MBs based on age, extent of resection and the Chang staging system. However, recent reports indicate that these clinical variables are inadequate methods of defining disease risk. This has prompted search for new markers for MB stratification. Recent studies indicate that the classification of MBs according to profiles of histopathology and molecular abnormalities possibly help better risk-stratification of patients, thereby rationalizing approaches to therapy, increasing cure rate, reducing long-term side effects and developing novel therapeutic strategies. The most accurate outcome prediction till date has been obtained through microarray gene expression profiling. In this article, the current histopathological classification and the recent advances in molecular genetics of MBs are reviewed. Global efforts to translate this knowledge of disease biology into clinical practice especially as outcome predictors are highlighted.

Brain Stem Neoplasms↗

PubMed1992

The role of risk stratification in the early management of a myocardial infarction.

OBJECTIVE: To review the literature on early management of myocardial infarction. DATA SOURCES: Papers published or referenced in major English-language cardiology journals for the last 15 years. STUDY SELECTION: Large recent multicenter studies and the guidelines for early management of patients with acute myocardial infarction (American College of Cardiology/American Heart Association Task Force) were emphasized. DATA SYNTHESIS: A strategy for risk stratification was developed from information available in the emergency department, from the first days of the hospitalization, and before discharge to identify patients in whom intervention might improve prognosis. CONCLUSIONS: Treatment of myocardial infarction requires establishing patency of the infarct-related artery, usually with thrombolysis. Risk stratification begins in the emergency department (phase 1) using clinical (primarily the electrocardiogram) and historical data to identify patients at risk for massive infarction. For patients at highest risk, the efficacy of thrombolytic therapy must be assured and, if not effective, emergency angiography and mechanical reperfusion should be considered. During days 2 to 5, (phase 2), patients with large amounts of ischemic myocardium, postinfarction angina, "flash" pulmonary edema, or anterior non-Q infarctions are identified and studied. Predischarge (phase 3) stratification identifies those patients at risk for early death. A previous infarction, an ejection fraction less than 0.40, pulmonary congestion during the hospitalization, delayed afterpotentials on signal-averaged electrocardiography, symptomatic ventricular ectopic beats, decreased heart rate variability, limited exercise tolerance, or ischemia on exercise testing identifies patients at high risk. Patients with jeopardized myocardium must be identified for revascularization to try to improve survival. More data are needed to determine whether angioplasty or bypass surgery will improve prognosis in these patients.

Algorithms↗

PubMed1999

Expression of galectin-7 during epithelial development coincides with the onset of stratification.

Galectin-7 is a 14 KDa member of the galectin family that we have cloned from human, rat and mouse. Our previous studies have shown that in the adult, galectin-7 is expressed in all cell layers of epidermis and of other stratified epithelia such asthe cornea and the lining of the oesophagus. This suggested that galectin-7 expression might be induced at a particular stage in the embryonic development of stratified epithelia. In the present study we have investigated this hypothesis by in situ hybridization of galectin-7 mRNA in mouse embryos. Starting from E13.5, weak expression of galectin-7 was detected in bilayered ectoderm, and stronger expression was found in areas of embryonic epidermis where stratification was more advanced. Galectin-7 expression was maintained in all living layers after epidermal development was completed. Galectin-7 was also strongly and specifically expressed in stratified regions of ectodermally-derived non-epidermal epithelia such as the lining of the buccal cavity, the oesophagus and the ano-rectal region. In contrast, no expression of galectin-7 was found in epithelia derived from endoderm, such as lining of the intestine, kidney and lung. Our results demonstrate that galectin-7 is expressed in all stratified epithelia examined so far, and that the onset of its expression coincides with the first visible signs of stratification. These results establish galectin-7 as the first region-independent marker of epithelial stratification.

Animals↗

PubMed2000

[Risk stratification after myocardial infarct].

In industrialized countries the rate of sudden cardiac death remains unchanged. The most frequently encountered structural heart disease in these patients is coronary artery disease. Despite the era of thrombolytic therapy of acute myocardial infarction patients carry an increased risk of sudden cardiac arrhythmogenic death within a time period of one to two years following the acute event. Therefore, risk stratification post-MI before patient discharge is furthermore mandatory. The spectrum of non-invasive techniques for risk stratification includes the clinical risk profile, measurement of left ventricular global function (LV ejection fraction), the resting ECG (QT dispersion), an ECG stress test (detection and severity of myocardial ischemia), ambulatory ECG monitoring (number and type of ventricular arrhythmias), surface high resolution ECG (detection of ventricular late potentials), measurement of T wave alternans (TWA, alternans ratio), and measurements of the activity and balance of the autonomous nervous system (heart rate variability, baroreflex sensitivity = BRS). Programmed ventricular stimulation (PVS) serves as an invasive risk stratification technique (detection of an arrhythmogenic substrate). The prognostic power of the non-invasive techniques is limited; in general, the prognostic value of a negative test is reasonably high (90 to 100% depending on the test used), whereas the prognostic value of a positive test is rather low (4 to 42% depending on the test used). Combining several non-invasive tests may significantly improve the positive predictive value above 50%, but this goes along with a significant decreases of sensitivity below 50%. Therefore, a combination of several non-invasive tests (detection and exclusion of a large number of low-risk individuals) with the invasive method of PVS (detection of an arrhythmogenic substrate, i.e. a high-risk patient) seems reasonable, as has been convincingly shown by several smaller prognostic studies.

Arrhythmias, Cardiac↗

PubMed2000

[The different meanings of the word stratification].

In clinical research, stratification has three different meanings. In its first meaning, it describes the natural distribution of patients into subgroups, for instance patients may be stratified by stage. In its second meaning, stratification controls the random allocation of the treatments in a clinical trial, for instance the randomisation can be stratified on stage. Lastly, in its third meaning, stratification of a trial analysis consists into taking into account patients' characteristics in the analysis. This three meanings will be illustrated with a basic example.

Humans↗

PubMed2001

Prediction of myocardial infarction versus cardiac death by gated myocardial perfusion SPECT: risk stratification by the amount of stress-induced ischemia and the poststress ejection fraction.

UNLABELLED: The combination of myocardial perfusion and poststress ejection fraction (EF) provides incremental prognostic information. This study assessed predictors of nonfatal myocardial infarction (MI) versus cardiac death (CD) by gated myocardial SPECT and examined the value of integrating the amount of ischemia and poststress EF data in risk stratification. METHODS: We identified 2,686 patients who underwent resting (201)Tl/stress (99m)Tc-sestamibi gated SPECT and were monitored for >1 y. Patients who underwent revascularization < or = 60 d after the nuclear test were censored from the prognostic analysis. Visual scoring of perfusion images used 20 segments and a scale of 0--4. Poststress EF was automatically generated. RESULTS: Cox regression analysis showed that after adjusting for prescan data, the most powerful predictor of CD was poststress EF, whereas the best predictor of MI was the amount of ischemia (summed difference score [SDS]). Integration of the EF and SDS yielded effective stratification of patients into low-, intermediate-, and high-risk subgroups. Patients with EF >50% and a large amount of ischemia were at intermediate risk (2%--3%), whereas those with mild or moderate ischemia were at low risk of CD (<1%/y). Patients with EF between 30% and 50% were at intermediate risk even in the presence of only mild or moderate ischemia. In patients with EF <30%, the CD rate was high (>4%/y) irrespective of the amount of ischemia. CONCLUSION: Poststress EF is the best predictor of CD, whereas the amount of ischemia is the best predictor of nonfatal MI. Integration of perfusion and function data improves stratification of patients into low, intermediate, and high risk of CD.

Adenosine↗