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Risk stratification by guidelines compared with risk assessment by risk equations applied to a MONICA sample.

BACKGROUND: The World Health Organization/International Society of Hypertension (WHO/ISH) Hypertension Guidelines from 1999 propose a risk stratification scheme for estimating absolute risk for cardiovascular disease (CVD). Risk equations estimated by statistical methods are another way of predicting cardiovascular risk. OBJECTIVE: We studied the differences between these two approaches when applied to the same set of individuals with high blood pressure. DESIGN AND METHODS: The two northernmost counties in Sweden (NSW) constitute one of the centres in the WHO MONICA (monitoring trends and determinants in cardiovascular disease) Project. Three population surveys have been carried out in 1986, 1990 and 1994, and were used to estimate a risk equation for predicting the 10-year risk of fatal/non-fatal stroke and myocardial infarction. Another MONICA sample from 1999, a total of 5997 subjects, was classified according to the recent WHO/ISH risk stratification scheme. A risk assessment was also performed, by using the risk equations from the NSW MONICA sample and Framingham risk equations. RESULTS: The agreement between the two methods was good when the values obtained from the risk equation were averaged for each risk group obtained from the risk classification by guidelines. However, if the predicted risk for each individual was considered, the agreement was poor for the medium and high-risk groups. Although the average risk for all individuals is the same, many subjects have a higher risk or a lower risk than predicted by guidelines. CONCLUSIONS: Risk classification by the 1999 WHO/ISH Hypertension Guidelines is not accurate and detailed enough for medium- and high-risk patients, which could be of clinical importance in the medium risk group.

Adult↗

"Sepsis/SIRS," physiologic classification, severity stratification, relation to cytokine elaboration and outcome prediction in posttrauma critical illness.

OBJECTIVE: To develop a quantitative severity stratification within the framework of a Physiologic State Classification (PSSC) system that can be applied to critically ill post-trauma patients with "sepsis/SIRS" and to relate PSSC to the nature of the plasma cytokine response. MATERIALS AND METHODS: At each study time period, a patient was classified into one of seven physiologic States previously derived from clustering 17 cardiopulmonary and metabolic variables from 338 critically ill patients: R = reference, A = normal stress response, B = metabolic insufficiency, C1 (early) and C2 (late) = respiratory insufficiency, D = cardiogenic insufficiency, H = nonshock hypovolemia. MAIN RESULTS: The PSSC used State data from a developmental set of 159 trauma patients in a logistic model (L2PDEATH) to provide a quantitative index of severity. This severity index was tested on 80 new trauma patients (mean injury Severity Score (ISS) = 27.6, 64% survivors). Using PSSC State distributions for evaluation of enzyme-linked immunosorbent assay (ELISA) measured cytokines interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF) showed the multicytokine score to be greatest in those C2- and B-State regions associated with a higher severity as measured by L2PDEATH. Compared with ARDEATH of the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system, L2PDEATH provided a better indicator of severity of sepsis/systemic inflammatory response syndrome (SIRS) for posttrauma patients. CONCLUSIONS: PSSC allows classification of the physiologic and cytokine mediator response to trauma and permits stratification of severity in posttrauma critical illness.

APACHE↗

Can risk stratification improve the management of acute upper-gastrointestinal bleeding?

Acute upper-gastrointestinal bleeding is a common indication for emergency admission to hospital. Risk-stratification scores have been devised to identify patients at risk of re-bleeding or death, but these have usually required both clinical and endoscopic assessment. Two recent studies have employed clinical criteria alone to identify low-risk patients that may not require admission or in-patient endoscopy. While each of these studies has individual merit, both are unable to answer the question of whether risk stratification improves health outcomes or resource use in acute gastrointestinal haemorrhage. They will nevertheless help the development of guidelines that enable patients to be managed more efficiently and outcomes to be compared more fairly.

Acute Disease↗

Left ventricular hypertrophy and cardiovascular risk stratification: impact and cost-effectiveness of echocardiography in recently diagnosed essential hypertensives.

BACKGROUND: Echocardiography is more accurate than electrocardiography in the assessment of cardiac target organ damage related to hypertension, thus leading to a more precise stratification of total cardiovascular risk. However, ultrasound examination of the heart on a routine basis remains a matter of debate. OBJECTIVE: To evaluate the impact and cost-effectiveness of echocardiographic examination on global risk stratification in low and medium-risk hypertensive patients in relation to age and sex. METHODS: A total of 580 untreated hypertensive individuals (355 men and 225 women, mean age 47.8 +/- 11.4 years), classified at low to medium risk, according to routine clinical work-up suggested by the 2003 European Society of Hypertension/European Society of Cardiology guidelines, were included in the study. Total risk was reassessed by adding the results of ultrasound examination of the heart. Left ventricular hypertrophy (LVH) was defined as a left ventricular mass index of 125 g/m2 or more in men and 110 g/m2 or more in women. The impact of LVH in stratifying risk was assessed according to age (< 50 and > or = 50 years) and sex. RESULTS: According to routine classification, 16.3% (n = 93) of the 580 patients were considered to be at low added risk and 83.7% (n = 487) at medium added risk. In the whole population, echocardiographic LVH was found in 86 patients (14.8%) who were then reclassified in the high-risk stratum. The prevalence rates of patients reclassified in the high-risk class as a consequence of LVH detection, according to age and sex, were as follows: 8.9% in men under 50 years, 12.3% in women under 50 years, 26.7% in men aged 50 years and over and 15.3% in women aged 50 years and over. The cost per detected case of LVH was 595 euros in patients under 50 years of age and 290 euros in those 50 years of age and older. CONCLUSIONS: Our findings indicate that the prevalence of LVH, and consequently the probability of upgrading the total cardiovascular risk profile, is highest in the group of old hypertensive men; echocardiography has a limited impact on the risk reclassification in younger patients and an unfavourable cost-effectiveness profile. Our data thus do not support the systematic ultrasound assessment of the heart in all uncomplicated hypertensive individuals.

Adult↗

Use of prognostic factors in risk stratification at diagnosis and time of treatment of patients with chronic lymphocytic leukemia.

PURPOSE OF REVIEW: To review risk stratification strategies used in chronic lymphocytic leukemia at diagnosis to predict aggressiveness of disease and, at time of treatment, to predict duration of response. RECENT FINDINGS: Several new prognostic factors can better assist clinicians in predicting the aggressiveness of chronic lymphocytic leukemia at diagnosis and the likelihood of maintaining a prolonged remission with treatment. This article reviews older prognostic factors such as beta2-microglobulin and thymidine kinase activity that have been partially validated by recently completed large studies. New prognostic factors such as interphase cytogenetics, immunoglobulin heavy-chain gene mutational analysis, and relevant secondary surrogate markers of immunoglobulin heavy-chain gene, including methylation of the zeta-associated protein gene, lipoprotein lipase overexpression, telomere length, and telomerase activity are reviewed. Some prognostic factors (interphase cytogenetics) but not others (immunoglobulin heavy-chain gene mutational status, zeta-associated protein expression) predict the duration of response to fludarabine-based combination strategies. SUMMARY: Recent advances in risk stratification provide clinicians with tools to better predict outcome of chronic lymphocytic leukemia at the time of treatment and response to treatment at the time of developing symptomatic disease.

Biomarkers, Tumor↗

A prognostic model for HIV seroconversion among injection drug users as a tool for stratification in clinical trials.

OBJECTIVE: The main goal of this study was to construct a prognostic model for HIV seroconversion among injection drug users (IDUs) using easy-to-measure risk indicators. DESIGN: Cox proportional hazards regression modeling was used for risk stratification in a heterogeneous population of IDUs with regards to HIV risk-taking behaviors. METHODS: Subjects were recruited in a prospective cohort of IDUs followed between September 1992 and October 2001. A total of 1602 men, seronegative at enrollment with at least 1 follow-up visit, were included in the analyses. Only variables that consistently predict HIV seroconversion in several settings were considered. The final model was used to assign a risk score for each participant. RESULTS: Three risk indicators were included in the risk score to predict HIV seroconversion: unstable housing, average cocaine injections per day, and having shared a syringe with a known HIV-positive partner. Kaplan-Meier survival functions were generated and risk score values stratified in 3 groups. HIV incidence rates per 100 person-years were as follows: 0.91 (95% CI, 0.55-1.52) for the low-risk group, 3.10 (95% CI, 2.49-3.84) for the moderate-risk group, and 7.82 (95% CI, 6.30-9.73) for the high-risk group (log-rank P value < 0.0001). CONCLUSION: If validated in other settings, this risk score may improve the prediction of outcome and allow more accurate stratification in clinical trials.

Adolescent↗

Intubation of pediatric trauma patients in the field: predictor of negative outcome despite risk stratification.

BACKGROUND: Recently, evidence has shown that intubation in the field may not improve or may even adversely affect outcomes. Our objective was to analyze outcomes in pediatric intubated trauma patients using a large national pediatric trauma registry. METHODS: The patient population was derived from the last phase of the National Pediatric Trauma Registry, comprising admissions from 1994 through 2002. Intubated patients were identified, as was their place of intubation: in the field, at a hospital that was not a trauma center, and at a trauma center. Risk stratification was performed for mortality using logistic regression models and variables available at presentation to the emergency room. Odds ratio and variable significance were calculated from the logistic regression model. The percentage of patients discharged to home and an abnormal Functional Independence Measure at hospital discharge examined functional outcome of survivors. RESULTS: There were a total of 50,199 patients, 5460 (11.6%) of whom were intubated (1,930 in the field, 1,654 in the hospital, and 1,876 in a trauma center). Unadjusted mortality rates for intubated patients were as follows: field, 38.5%; hospital, 16.7%; and trauma center, 13.2% (all different, p < 0.05). The developed logistic regression model had an area under the receiver operating characteristic curve of 0.98. Compared with nonintubated patients, the odds ratio for field intubation, for non-trauma center, and for trauma center intubation was 14.4, 5.8, and 4.8, respectively (significantly different field vs. either hospital). The actual (observed) death rate was significantly higher than predicted in those intubated in the field. Stratification of injury by New Injury Severity Score or degree of head injury showed that this difference extended from mild to severe (e.g., odds ratio for New Injury Severity Score < 15 field vs. trauma center intubation, 12.3; odds ratio for none or moderate head injury, 5.1). Similar results were obtained for functional outcome in the survivors. CONCLUSION: Field intubation is an independent strong negative predictor of survival or good functional outcome despite adjustment for severity of injury. Although not causal, the magnitude of these differences should lead to future controlled studies of pediatric trauma field intubations.

Abbreviated Injury Scale↗

p63 is the molecular switch for initiation of an epithelial stratification program.

Development of stratified epithelia, such as the epidermis, requires p63 expression. The p63 gene encodes isoforms that contain (TA) or lack (DeltaN) a transactivation domain. We demonstrate that TAp63 isoforms are the first to be expressed during embryogenesis and are required for initiation of epithelial stratification. In addition, TAp63 isoforms inhibit terminal differentiation, suggesting that TAp63 isoforms must be counterbalanced by DeltaNp63 isoforms to allow cells to respond to signals required for maturation of embryonic epidermis. Our data demonstrate that p63 plays a dual role: initiating epithelial stratification during development and maintaining proliferative potential of basal keratinocytes in mature epidermis.

Animals↗

Stripes ordering in self-stratification experiments of binary and ternary granular mixtures

The self-stratification of binary and ternary granular mixtures has been experimentally investigated. Ternary mixtures lead to a particular ordering of the strata which was not accounted for in former explanations. Bouncing grains are found to have an important effect on stratum formation. A complementary mechanism for self-stratification of binary and ternary granular mixtures is proposed.

Journal Article↗

Particle density stratification in transient sedimentation.

Theoretical predictions for the scaling of particle velocity fluctuations with container size in homogeneous Stokes suspensions are not consistent with experimental observations. Several explanations have been advanced, including the formation of stratification in bounded systems, such as those used in experiments. Numerical simulations of transient Stokes sedimentation in bounded cells are presented here for several cell sizes. The simulated cells have top and bottom wall boundaries and periodic boundaries in the horizontal. Throughout the course of the simulations the number and distribution of particles in the cell evolve, with impacts on the bulk mean particle velocity, velocity fluctuations, and particle density gradient. Initially the sedimentation follows the classical description, with a sharp front and uniform particle concentration below, but this is not sustained. A layer of higher particle concentration develops below the front. This is unstable and there is a large-scale overturning of the fluid. As a consequence, there is a redistribution of the particles, leaving behind a mass loading of the particles, which is stably stratified (subject to small density fluctuations between horizontal levels). The mean velocity and fluctuations of the particles initially grow and then decay once stable stratification has developed.

Journal Article↗

High Energy Charge as a Requirement for Axis Elongation in Response to Gibberellic Acid and Kinetin during Stratification of Acer saccharum Seeds.

The growth potential of embryonic axes of Acer saccharum Marsh. increased during moist storage at 5 C but not at 20 C. During the period of increasing growth potential, the oxygen consumption of the axes remained constant. It was possible to distinguish three phases of the stratification-germination process at 5 C with respect to response of the axis to gibberellic acid and kinetin. From 0 to 10 days the growth regulators had no effect on elongation; from 10 to 60 days axis elongation was stimulated; and between day 60 and day 75, when germination had begun, the growth substances were inhibitory. The adenylate energy charge remained low (0.15) in axes of dry dormant seeds but increased to 0.78 following imbibition of water and 10 days of moist storage at 5 C. This phenomenon was not specifically related to low temperature stratification, since a rapid increase in the energy charge of the axes also occurred following imbibition and moist storage at 20 C. The excised axes would elongate in response to the growth substances only when a high energy charge (approximately 0.8) was maintained.

Journal Article↗

Imbibition, but not release from stratification, sets the circadian clock in Arabidopsis seedlings.

Circadian rhythms in the abundance of the CAT2 catalase mRNA were not seen in etiolated seedlings but developed upon illumination. These circadian oscillations were preceded by a rapid and transient induction of CAT2 mRNA abundance that varied strikingly according to the timing (circadian phase) of the onset of illumination. This variation oscillated with a circadian periodicity of approximately 28 hr, indicating that the circadian oscillator is running in etiolated seedlings and regulates (gates) the induction of CAT2 by light. Moreover, because we assayed populations of seedlings, we infer that the individual clocks among populations of etiolated seedlings were synchronized before the onset of illumination. What developmental or environmental signals synchronized the clocks among seedlings? Varying the phase of the onset of illumination relative to release from stratification failed to affect the acute induction of CAT2, indicating that the temperature step from 4 to 22 degrees C associated with release from stratification did not reset the circadian clock. However, the acute induction of CAT2 mRNA varied with time after imbibition, demonstrating that imbibition provides a signal capable of resetting the circadian clock and of synchronizing the clocks among populations of seedlings.

Arabidopsis↗

Role of electrophysiologic studies, signal-averaged electrocardiography, heart rate variability, T-wave alternans, and loop recorders for risk stratification of ventricular arrhythmias.

Ventricular tachycardia and fibrillation are major causes of morbidity and mortality after myocardial infarction. Frequently, sudden cardiac death is the first manifestation of such malignant rhythms. Optimal risk stratification strategies in this population are of utmost importance. In this review the authors discuss the background and clinical use of invasive tests, such as electrophysiologic study and implantable loop recorders, and noninvasive tests, such as signal-averaged electrocardiography, heart rate variability, and T-wave alternans. The utility, indications, and limitations of each test in clinical practice are discussed, especially for the purpose of postmyocardial infarction risk stratification in the elderly population.

Action Potentials↗

United Network for Organ Sharing's expanded criteria donors: is stratification useful?

The United Network for Organ Sharing (UNOS) Expanded Criteria Donor (ECD) system utilizes pre-transplant variables to identify deceased donor kidneys with an increased risk of graft loss. The aim of this study was to compare the ECD system with a quantitative approach, the deceased donor score (DDS), in predicting outcome after kidney transplantation. We retrospectively reviewed 49 111 deceased donor renal transplants from the UNOS database between 1984 and 2002. DDS: 0-39 points; >or=20 points defined as marginal. Recipient outcome variables were analyzed by ANOVA or Kaplan-Meier method. There was a 90% agreement between the DDS and ECD systems as predictors of renal function and graft survival. However, DDS identified ECD- kidneys (10.7%) with a significantly poorer outcome than expected (DDS 20-29 points, n = 5,252). Stratification of ECD+ kidneys identified a group with the poorest outcome (DDS >or=30 points). Predictability of early post-transplant events (i.e. need for hemodialysis, decline of serum creatinine and length of hospital stay) was also improved by DDS. DDS predicted outcome of deceased donor renal transplantation better than the ECD system. Knowledge obtained by stratification of deceased donor kidneys can allow for improved utilization of marginal kidneys which is not achieved by the UNOS ECD definition alone.

Adult↗

Aerobic methane oxidation and methanotroph community composition during seasonal stratification in Mono Lake, California (USA).

Patterns of aerobic methane (CH4) oxidation and associated methanotroph community composition were investigated during the development of seasonal stratification in Mono Lake, California (USA). CH4 oxidation rates were measured using a tritiated CH4 radiotracer technique. Fluorescence in situ hybridization (FISH), denaturing gradient gel electrophoresis (DGGE) and sequence analysis were used to characterize methanotroph community composition. A temporally shifting zone of elevated CH4 oxidation (59-123 nM day(-1)) was consistently associated with a suboxycline, microaerophilic zone that migrated upwards in the water column as stratification progressed. FISH analysis revealed stable numbers of type I (4.1-9.3 x 10(5) cells ml(-1)) and type II (1.4-3.4 x 10(5) cells ml(-1)) methanotrophs over depth and over time. Denaturing gradient gel electrophoresis and sequence analysis indicated slight shifts in methanotroph community composition despite stable absolute cell numbers. Variable CH4 oxidation rates in the presence of a relatively stable methanotroph population suggested that zones of high CH4 oxidation resulted from an increase in activity of a subset of the existing methanotroph population. These results challenge existing paradigms suggesting that zones of elevated CH4 oxidation activity result from the accumulation of methanotrophic biomass and illustrate that type II methanotrophs may be an important component of the methanotroph population in saline and/or alkaline pelagic environments.

Aerobiosis↗

Socio-economic stratification generated by international migration loops.

This paper analyzes the migration phenomenon within a framework that treats migration movements as continuous loops, from the country of origin to the destination and back. Significant social-psychological factors at each step of the loop process contribute to the development of migration streams along a predictable pattern. The general model of the loop process shows that the migration stream is 1st sparked when labor is recruited from less developed countries for work in developed industrialized countries. Once the social process of migration has begun, it tends to acquire a self-feeding character. Social and economic change in sending and receiving societies brought about by migration make further migration more likely. The case of the Mexico-US-Mexico loop process is analyzed. This case illustrates the effects of socioeconomic stratification that occurs in communities where the migration loop process reaches a certain level of maturity. The majority of a town's population may become committed to migration as a way of life. Eventually, wealth becomes concentrated in the hands of those that are most able to migrate. Thus, migrants may become a new elite segment of rural populations that were once relatively homogenous societies. Further research of the migration loop process should be conducted. At least in the case of Mexico, the socioeconomic stratification in the villages and towns acting as sources of migration loops with destinations in the US have significant internal economic, social, and political implications.

Americas↗

Stratification by cyanobacteria in lakes: a dynamic buoyancy model indicates size limitations met by Planktothrix rubescens filaments.

The ability of the Planktothrix rubescens to stratify in Lake Zürich is related to the size and shape of the cyanobacterial filaments. Detailed measurements made in the lake are used in a dynamic computer model of buoyancy regulation to investigate the vertical movements of filaments tracking the depth at which the irradiance would support neutral buoyancy. The movement of the filament lags behind the constantly changing target depth owing to (a) the time taken for the filament to respond to the irradiance by changing its density and (b) the time it takes to move by sinking down or floating up through the water column. The model simulates the stratification depth over a 5-month period of the summer from the continuous measurements of irradiance and weekly measurements of light attenuation and temperature, without any further adjustment over the period. Models using filaments of the size observed in Lake Zürich explain several details of the observed depth changes: smaller planktonic cyanobacteria (e.g. Limnothrix sp.) are unable to migrate fast enough and larger ones (e.g. Anabaena spp.) will overshoot and become entrained in the epilimnion. The model can be used to simulate recruitment of Planktothrix filaments from different depths after vernal stratification. Recruitment of filaments from depths down to 45 m will contribute to the metalimnetic population increase in early July.

Cyanobacteria↗

Cardiovascular disease risk stratification and comparison in a California population.

This study was designed to identify the need for primary prevention of cardiovascular disease in an HMO population and to develop appropriate interventions for individuals in different risk groups, based on risk stratification and comparison. The analysis is based on a cross-sectional survey of the HMO members of a large employer group. Respondents (n=17,878) were stratified based on the Framingham model; 34% of respondents without cardiovascular disease were classified as moderate to high attributable risk for the disease, and 66% were classified as low attributable risk. Results of logistic regression analyses suggest that, compared with respondents with pre-existing cardiovascular disease, moderate- to high-risk respondents are more likely to smoke, have unhealthy diets, and be overweight, hypertensive, and hypercholesterolemic. More low-risk respondents had unhealthy diets than did those with pre-existing cardiovascular disease. There were no differences between these groups for physical activity and stress. Respondents had fewer modifiable risk factors and healthier lifestyles than did those who were at risk. These findings suggest that primary prevention should be enhanced, especially among those with significantly increased risk for the disease. Moreover, the approaches of this project-population-based risk assessment, stratification, and comparison-were instrumental in identifying the target population and designing appropriate interventions. (c) 2001 by CHF, Inc.

Journal Article↗