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PubMed2006

C-reactive protein and echocardiography have little impact on risk stratification in never-treated hypertensive patients.

The aim of this study was to assess the contribution of increased concentrations of high-sensitivity C-reactive protein (hsCRP) and echocardiography to risk stratification according to the 2003 European guidelines for the management of arterial hypertension in patients with untreated hypertension. A total of 207 consecutive medical outpatients with untreated hypertension were included. History and clinical examination, electrocardiography, laboratory analyses including the measurement of hsCRP and echocardiography were performed in all patients. Patients were classified into four risk groups with and without using echocardiography and hsCRP concentrations of at least 10 mg/l according to the 2003 guidelines for the management of hypertension. The majority of the 207 patients (81%) were at moderate or high cardiovascular risk before adding echocardiography and/or hsCRP to the risk stratification process. When echocardiography was included, only three patients were reclassified from the moderate added risk to the high added risk group. Adding hsCRP concentrations of at least 10 mg/l had no impact on risk stratification. Using an hsCRP cutoff level of 3 mg/l, one patient was at moderate instead of low added risk, eight patients were at high instead of moderate added risk and one patient was at very high instead of high added risk. We conclude that hsCRP at the proposed cutoff level of 10 mg/l has no impact on risk stratification in outpatients with untreated hypertension. An hsCRP cutoff level of 3 mg/l may be more suitable for risk stratification. Finally, our data suggest that depending on the population studied, there is minimal impact of echocardiography on risk stratification.

C-Reactive Protein↗

PubMed1983

Protein Changes during the Stratification of Malus domestica Borkh. Seed.

Apple seeds (Malus domestica Borkh. cv Golden Delicious) were stratified at 5 and 15 degrees C for various lengths, weighed, and soluble protein of axis and cotyledon tissue was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Only seeds treated at 5 degrees C germinated; seeds treated at 15 degrees C did not germinate. Optimal germination required 63 days of stratification. Excised embryos required less stratification time for germination than intact seeds. When stratification was less than 35 days, the resulting seedlings from 5 degrees C stratified embryos were dwarfed and epinastic. After 63 days of stratification, axes from 5 and 15 degrees C treated intact seeds had increased in fresh weight by 72 and 28% (w/w), respectively. The dry weights of the axes did not change significantly and both fresh and dry weights of cotyledons remained unchanged during stratification. Total soluble protein in axes and cotyledons changed very little during stratification. However, axis polypeptide profiles changed. Most obvious was the occurrence of a new polypeptide and the increase of four other clearly identifiable polypeptides during 5 degrees C treatment. The levels of the five most predominant axis proteins decreased at the same time. We observed no changes in the profiles of soluble cotyledon proteins. Control seeds kept at -10 degrees C showed none of the reported changes.

Journal Article↗

PubMed1997

Risk assessment and risk stratification in sudden cardiac death: a biostatistician's view.

Determining individual probabilities of developing lethal arrhythmia over time (risk assessment) and grouping individuals by that probability (risk stratification) are similar to, yet differ in purpose from, screening, diagnosis, risk factor identification, and prognostic staging. Methods of handling bias, use of multiple predictors, and evaluation of results provide challenges. A key purpose of risk assessment and stratification is examined. The role of operational definitions of predictors and events and of methods that account for multiple predictors and known confounding factors is analyzed. Constructed examples illustrate potential pitfalls in assessment and how multivariate techniques can deal with multiple predictors. A trial design to evaluate risk stratification for the identified purpose is elaborated and potential results are interpreted. Bias from predictors regressing to the mean can be minimized either by averaging a number of measurements or by equalizing the bias in comparison groups. An analysis of two predictors and two risk strata illustrates how the discrimination of combined predictors may be greater than the sum of the individual variables' discrimination. Risk stratification can be evaluated in trials that randomize competing interventions within different risk strata. Results of such trials indicate whether the risk strata adequately distinguish individuals by their responsiveness to particular intervention. Potential pitfalls, not easily recognized in risk stratification, can be avoided in the methods and in studies for evaluating those methods. Multivariate techniques maximize the discrimination of multiple predictors, but may increase complexity. Randomized trials of treatment provide evidence for utility of risk stratification.

Arrhythmias, Cardiac↗

PubMed2005

The bias introduced by population stratification in IBD based linkage analysis.

The lack of replication of model-free linkage analyses performed on complex diseases raises questions about the robustness of these methods to various biases. The confounding effect of population stratification on a genetic association study has long been recognized in the genetic epidemiology community. Because the estimation of the number of alleles shared identical by descent (IBD) does not depend on the marker allele frequency when founders of families are observed, model-free linkage analysis is usually thought to be robust to population stratification. However, for common complex diseases, the genotypes of founders are often unobserved and therefore population stratification has the potential to impair model-free linkage analysis. Here, we demonstrate that, when some or all of the founder genotypes are missing, population stratification can introduce deleterious effects on various model-free linkage methods or designs. For an affected sib pair design, it can cause excess false-positive discoveries even when the trait distribution is homogeneous among subpopulations. After incorporating a control group of discordant sib pairs or for a quantitative trait, two circumstances must be met for population stratification to be a confounder: the distributions for both the marker and the trait must be heterogeneous among subpopulations. When this occurs, the bias can result in either a liberal, and hence invalid, test or a conservative test. Bias can be eliminated or alleviated by inclusion of founders' or other family members' genotype data. When this is not possible, new methods need to be developed to be robust to population stratification.

Bias↗

PubMed1996

Income, social stratification, class, and private health insurance: a study of the Baltimore metropolitan area.

Most studies of inequalities and access to health care have used income as the sole indicator of social stratification. Despite the significance of social theory in health insurance research, there are no empirical studies comparing the ability of different models of social stratification to predict health insurance coverage. The aim of this study is to provide a comparative analysis using a variety of theory-driven indicators of social stratification and assess the relative strength of the association between these indicators and private health insurance. Data were collected in a 1993 telephone interview of a random digit dialing sample of the white population in the Baltimore Metropolitan Statistical Area. Indicators of social stratification included employment status, full-time work, education, occupation, industry, household income, firm size, and three types of assets: ownership, organizational, and skill/credential. The association between social stratification and private health insurance was strongest for those having higher household incomes, having attained at least a bachelor's degree, and working in a firm with more than 50 employees, followed by being an owner or manager, and by being employed. The addition of education and firm size improved the prediction of the household income model. The authors conclude that studies of inequalities in health insurance coverage can benefit from the inclusion of theory-driven indicators of social stratification such as human capital, labor market segmentation, and control over productive assets.

Adult↗

PubMed2003

[Cluster analysis applied in the epidemiological stratification analysis].

OBJECTIVE: To establish a new method on stratification analysis when the stratification limits of confounding factors was not clear or contradictory. METHOD: Data on a study of diabetes mellitus in Guangdong province collected in the year of 1997 and 1998 was analyzed using cluster-stratification analysis. RESULTS: The efficiency of stratification analysis was improved and the confounding bias was effectively controlled with information bias avoided when the clusters-stratification analysis was applied. CONCLUSION: The problem was logically solved using cluster analysis as an assistant stratification means.

Adult↗

PubMed2026

Research progress and application prospects of multi-omics integration strategies in precision risk stratification of type 1 diabetes mellitus.

Type 1 diabetes (T1D) is a chronic metabolic disease mediated by autoimmunity. Its pathogenesis involves complex interactions between genetic susceptibility and environmental factors. Conventional T1D risk stratification primarily relies on genetic markers, islet autoantibodies, and glycemic indicators. Although these biomarkers remain indispensable in current clinical practice, they are often insufficient when used alone to accurately identify ultra-early high-risk individuals, predict disease progression rates, or support individualized preventive strategies. Consequently, more comprehensive molecular approaches are needed to improve precision risk stratification. In recent years, the rapid development of multi-omics technologies has provided new strategies for precise risk stratification of T1D. This narrative review critically evaluates how multi-omics integration strategies can improve precision risk stratification throughout the T1D disease continuum by integrating complementary molecular information from genomics, transcriptomics, proteomics, metabolomics, epigenomics, and the microbiome. Particular emphasis is placed on stage-specific biomarker discovery, multi-omics data integration frameworks, artificial intelligence-assisted prediction models, biomarker validation, and the opportunities and challenges associated with clinical translation. Current evidence suggests that integrated multi-omics approaches have the potential to improve risk prediction accuracy, distinguish heterogeneous disease trajectories, identify individuals at imminent risk of progression, and provide biologically informed targets for precision intervention. However, important challenges remain, including data harmonization, external validation, model interpretability, cost-effectiveness, and integration into routine clinical screening programs. Future research should prioritize prospective multicenter cohorts, standardized analytical pipelines, externally validated prediction models, and clinically interpretable multi-omics frameworks to facilitate the translation of precision risk stratification into routine T1D prevention and management.

Humans↗

PubMed2005

Risk stratification models fail to predict hospital costs of cardiac surgery patients.

BACKGROUND: The aim of this prospective study was to determine if commonly used risk stratification models can predict total hospital costs in cardiac surgical patients. METHODS: Between October 1st and December 31st 2003, all consecutive adult patients undergoing cardiac surgery on CPB at our institution were classified using seven risk stratification scoring systems: EuroSCORE, Cleveland, Parsonnet, Ontario, French, Pons, and CABDEAL. Total hospital costs for each patient were calculated on a daily basis including preoperative diagnostic tests, operating room costs, disposable materials, drugs, blood components, costs for personnel, and hospital fixed-costs. Linear regression analysis was used to determine the correlation between costs and the seven risk stratifications models as well as length of stay (LOS) on ICU. The Spearman correlation coefficient was calculated from the regression line, and an analysis of residuals was performed to determine the quality of the regression. RESULTS: A total of 252 patients were operated for CABG (n=175), valve (n=39), CABG plus valve (n=21), thoracic aorta (n=13) and miscellaneous (2 myxoma, 1 ASD, 1 pulmonary embolism). Mean age of the patients was 66.0+/-11.4 years, 29.4% were female. LOS on ICU was 3.3+/-6.3 days and the 30-day mortality rate was 6.7%. Spearman correlation between the seven risk stratification models and hospital costs was below r=0.32 (p=0.0001), but was r=0.94 (p=0.0001) between ICU LOS and costs. CONCLUSIONS: Total hospital costs can be identified by length of ICU stay. None of the common risk stratification models accurately predicted total hospital costs in cardiac surgical patients.

Aged↗

PubMed2002

CYP3A4-V and prostate cancer in African Americans: causal or confounding association because of population stratification?

CYP3A4-V, an A to G promoter variant associated with prostate cancer in African Americans, exhibits large differences in allele frequency between populations. Given that the African American population is genetically heterogeneous because of its African ancestry and subsequent admixture with European Americans, case-control studies with African Americans are highly susceptible to spurious associations. To test for association with prostate cancer, we genotyped CYP3A4-V in 1376 (2 N) chromosomes from prostate cancer patients and age- and ethnicity-matched controls representing African Americans, Nigerians, and European Americans. To detect population stratification among the African American samples, 10 unlinked genetic markers were genotyped. To correct for the stratification, the uncorrected association statistic was divided by the average of association statistics across the 10 unlinked markers. Sharp differences in CYP3A4-V frequencies were observed between Nigerian and European American controls (0.87 and 0.10, respectively; P<0.0001). African Americans were intermediate (0.66). An association uncorrected for stratification was observed between CYP3A4-V and prostate cancer in African Americans (P=0.007). A nominal association was also observed among European Americans (P=0.02) but not Nigerians. In addition, the unlinked genetic marker test provided strong evidence of population stratification among African Americans. Because of the high level of stratification, the corrected P-value was not significant (P=0.25). Follow-up studies on a larger dataset will be needed to confirm whether the association is indeed spurious; however, these results reveal the potential for confounding of association studies by using African Americans and the need for study designs that take into account substructure caused by differences in ancestral proportions between cases and controls.

Adult↗

PubMed1997

The integration of two health systems: social stratification, work and health in East and West Germany.

This is an analysis of system integration, social stratification and work for health status and health care in East and West Germany. It is based on aggregate data and representative survey data of random samples of 2554 adults in both subsystems. Findings show that there were marked differences in life-expectancy prior to unification. The integration of the two systems, which occurred almost totally with regard to terms of West German health care organization, shows adjustment problems in the East for the public Health-Care-Funds and few if any for ambulatory care. The work situation has an impact on health, but there are no significant differences for East versus West. Social stratification variables show an influence on subjective health status for education (East) and for income, social status (West), while physician utilization (despite a preference of specialists by those with higher status) is not significantly determined by stratification variables in either East or West Germany. Beyond the central focus on work and stratification determinants a major finding pertains to a comparatively worse health situation for the aged and for women in what was the former East Germany. System models of Capitalism versus Socialism fit the results and recent history of the two systems to only a limited degree, as the West German corporate health system shows clear limits in following free market principles. The East German system, regardless of its centralized organization and move towards a socialist system, never fully abandoned the traditional model of German health care. Unlike the East German health system, that of West Germany, with its general expansion to 92% of the population, shows an increasing effect for social redistribution. The latter may be a reason why standard indicators of social stratification show less of an impact on health and health care than expected, while conditions at work clearly determine the health of people-the latter being the case in both the former East and West Germany.

Adult↗

PubMed2001

Risk stratification. A practical approach to using epiluminescence microscopy/dermoscopy in melanoma screening.

Risk stratification of pigmented lesions during melanoma screening is a method of classifying lesions into groups based on their relative risk of being melanoma. Risk stratification accepts the fact that clinical examination with and without ELM is not perfect but uses potential ELM clues to early melanoma to increase the sensitivity of screening. Risk stratification permits the use of all available a priori clinical information and the physician's judgement in making a final management decision for each lesion and for each patient. Risk stratification using ELM is based on two primary concepts: (1) a pigment network suggests a lesion is melanocytic and (2) melanoma causes the network to develop heterogeneous (i.e., irregular) and eccentric (i.e., not centered) pigmentation. In applying ELM risk stratification to melanoma screening the physician follows these four steps: 1. Inspect each lesion carefully for a pigment network. 2. If a pigment network is seen, group lesions by their relative degrees of heterogeneity and eccentricity of the pigment network. 3. If a network is not seen, look for typical patterns of benign lesions and melanoma mimickers. 4. Use the resulting clinical risk class to guide management using all available clinical information combined with clinical judgment.

Decision Trees↗

PubMedDate not supplied

Development of cholinergic amacrine cell stratification in the ferret retina and the effects of early excitotoxic ablation.

The present study has examined the emergence of cholinergic stratification within the developing inner plexiform layer (IPL), and the effect of ablating the cholinergic amacrine cells on the formation of other stratifications within the IPL. The population of cholinergic amacrine cells in the ferret's retina was identified as early as the day of birth, but their processes did not form discrete strata until the end of the first postnatal week. As development proceeded over the next five postnatal weeks, so the positioning of the cholinergic strata shifted within the IPL toward the outer border, indicative of the greater ingrowth and elaboration of processes within the innermost parts of the IPL. To examine whether these cholinergic strata play an instructive role upon the development of other stratifications which form within the IPL, one-week-old ferrets were treated with L-glutamate in an attempt to ablate the population of cholinergic amacrine cells. Such treatment was shown to be successful, eliminating all of the cholinergic amacrine cells as well as the alpha retinal ganglion cells in the central retina. The remaining ganglion cell classes as well as a few other retinal cell types were partially reduced, while other cell types were not affected, and neither retinal histology nor areal growth was compromised in these ferrets. Despite this early loss of the cholinergic amacrine cells, which are eliminated within 24 h, other stratifications within the IPL formed normally, as they do following early elimination of the entire ganglion cell population. While these cholinergic amacrine cells are present well before other cell types have differentiated, apparently neither they, nor the ganglion cells, play a role in determining the depth of stratification for other retinal cell types.

Aging↗

PubMed2001

Palaeoceanography. Antarctic stratification and glacial CO2.

One way of accounting for lowered atmospheric carbon dioxide concentrations during Pleistocene glacial periods is by invoking the Antarctic stratification hypothesis, which links the reduction in CO2 to greater stratification of ocean surface waters around Antarctica. As discussed by Sigman and Boyle, this hypothesis assumes that increased stratification in the Antarctic zone (Fig. 1) was associated with reduced upwelling of deep waters around Antarctica, thereby allowing CO2 outgassing to be suppressed by biological production while also allowing biological production to decline, which is consistent with Antarctic sediment records. We point out here, however, that the response of ocean eddies to increased Antarctic stratification can be expected to increase, rather than reduce, the upwelling rate of deep waters around Antarctica. The stratification hypothesis may have difficulty in accommodating eddy feedbacks on upwelling within the constraints imposed by reconstructions of winds and Antarctic-zone productivity in glacial periods.

Antarctic Regions↗

PubMed1998

Stratification does not limit O2 uptake in rabbit lungs.

This study was performed to assess the role of stratification, i.e. axial gas mixing deficit within alveolar space, in limiting alveolar gas exchange for oxygen. The single-breath method for varying breath-holding time with oxygen-labelled carbon dioxide, C18O2, was applied to 10 anaesthetized, paralysed and artificially ventilated rabbits. Alveolar partial pressure of C18O2 was analysed using respiratory mass spectrometry. Starting from residual volume, the lungs were rapidly inflated using 40 mL of indicator gas mixture (1% C18O2 in nitrogen). After executing breath-holding, the lungs were rapidly deflated. Pulmonary diffusing capacity of carbon monoxide was determined in the same way. On the basis of a serial compartment model, the lower limit of the stratificational conductance of oxygen was estimated, using the rate constant of C18O2 removal from alveolar space (4 s-1) and Graham's law. We found that the stratificational conductance in rabbits amounts to at least 13.5 mL mmHg-1 min-1. The pulmonary diffusing capacity of oxygen was calculated by multiplying the carbon monoxide diffusing capacity of rabbit lungs by a factor of 1.2, yielding a value of 0.77 mL mmHg-1 min-1. These results show that stratificational conductance is at least 17.5 times higher than pulmonary oxygen diffusing capacity, indicating that stratification does not limit oxygen uptake in rabbit lungs.

Animals↗

PubMed2002

Risk stratification theme for congenital heart surgery.

Surgical practice is changing and auto-evaluation of quality of care, organized by scientific societies, is very likely to become an obligation during this new decade. This evaluation requires a common nomenclature, a registry, and risk stratification. The primary purpose of risk stratification is to offer the possibility of objective analysis of surgical outcomes according to the complexity of the pathology treated. Registries, databases containing select essential data on a complete population, are not able to produce a statistically reliable risk stratification model. Academic databases, like that of the Congenital Heart Surgeons Society, contain comprehensive data on select patients, and are able to produce risk stratification, but only very slowly. The absence of risk discrimination in current registries penalizes centers treating complex pathologies. They may be reluctant to release their results without the security of risk stratification. Given the diversity of congenital heart surgery, a new method has been developed to stratify risks: the complexity score. This approach is based on the perceived opinions of a group of 50 internationally recognized surgeons and centers. It allows a hierarchical classification of surgical procedures according to mortality, morbidity, and surgical difficulty. Surgical procedures are scored globally on simple pathologies and in detail according to seven categories of risks. The complexity score in congenital heart surgery, also known as the Aristotle Score, is currently being developed as a collaborative effort of the members of the European Association for Cardio-thoracic Surgery, the Society of Thoracic Surgeons, the Congenital Heart Surgeons Society, and the European Congenital Heart Surgeons Foundation, and should be available next year.

Databases, Factual↗

PubMed2000

Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias.

BACKGROUND: Some critics argue that bias from population stratification (the mixture of individuals from heterogeneous genetic backgrounds) undermines the credibility of epidemiologic studies designed to estimate the association between a genotype and the risk of disease. We investigated the degree of bias likely from population stratification in U.S. studies of cancer among non-Hispanic Caucasians of European origin. METHODS: An expression of the confounding risk ratio-the ratio of the effect of the genetic factor on risk of disease with and without adjustment for ethnicity-is used to measure the potential relative bias from population stratification. We first use empirical data on the frequency of the N-acetyltransferase (NAT2) slow acetylation genotype and incidence rates of male bladder cancer and female breast cancer in non-Hispanic U.S. Caucasians with ancestries from eight European countries to assess the bias in a hypothetical population-based U.S. study that does not take ethnicity into consideration. Then, we provide theoretical calculations of the bias over a large range of allele frequencies and disease rates. RESULTS: Ignoring ethnicity leads to a bias of 1% or less in our empirical studies of NAT2. Furthermore, evaluation of a wide range of allele frequencies and representative ranges of cancer rates that exist across European populations shows that the risk ratio is biased by less than 10% in U.S. studies except under extreme conditions. We note that the bias decreases as the number of ethnic strata increases. CONCLUSIONS: There will be only a small bias from population stratification in a well-designed case-control study of genetic factors that ignores ethnicity among non-Hispanic U.S. Caucasians of European origin. Further work is needed to estimate the effect of population stratification within other populations.

Alleles↗

PubMed1999

The development of retinal ganglion cell dendritic stratification in ferrets.

A signature feature of mature ferret retinal ganglion cells (RGCs) is the stratification of their dendrites within either ON or OFF sublayers of the retinal inner plexiform layer (IPL). Dendritic stratification is achieved through the gradual restriction of RGC dendrites which initially ramify throughout the IPL. We examined the time course of stratification by retrogradely labeling ferret retinas with DiI at various postnatal ages. Stratification of beta and alpha RGC dendrites into either the ON or OFF sublayers of the IPL begins around postnatal day 5, when class-specific morphologies begin to emerge, and is largely completed by eye opening, at the end of the first postnatal month. Our results imply that dendritic stratification of ferret ON and OFF RGCs, as in other mammals, occurs independently of visually driven activity.

Aging↗

PubMed2002

Three-year prospective validation of a pre-endoscopic risk stratification in patients with acute upper-gastrointestinal haemorrhage.

OBJECTIVE: To assess the accuracy of a risk stratification that is used at initial assessment to identify groups with increased risk of mortality and requirement for urgent treatment intervention. DESIGN: Prospective assessment of risk stratification in consecutive patients with acute upper-gastrointestinal haemorrhage. METHODS: Over a 3-year period, 1349 consecutive patients with acute upper-gastrointestinal haemorrhage presenting to a single teaching hospital were prospectively risk stratified before endoscopy and followed up for outcome. MAIN OUTCOME MEASURES: Two-week, all-cause mortality, re-bleeding, and need for urgent treatment intervention. RESULTS: Stratification within the high-risk group predicted a significant increased risk of 2-week, all-cause mortality (P < 0.001) when compared with intermediate- and low-risk patients (11.8%, 3% and 0%, respectively), re-bleeding (P < 0.001) (44.1%, 2.3% and 0%, respectively), and need for urgent treatment intervention (P < 0.001) (71%, 40.6% and 2.6%, respectively). CONCLUSIONS: Over a 3-year period, medical staff at this institution have routinely used this risk stratification, which identifies groups of patients at high and low risk of mortality, re-bleeding and need for urgent treatment intervention following acute upper-gastrointestinal haemorrhage. Use of this risk stratification should allow targeting of more intensive treatment where it might be of most benefit. Those patients at lowest risk from outpatient management are also identified.

Acute Disease↗