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Identifiability, stratification and minimum variance estimation of causal effects.

The weakest sufficient condition for the identifiability of causal effects is the weakly ignorable treatment assignment, which implies that potential responses are independent of treatment assignment in each fine subpopulation stratified by a covariate. In this paper, we expand the independence that holds in fine subpopulations to the case that the independence may also hold in several coarse subpopulations, each of which consists of several fine subpopulations and may have overlaps with other coarse subpopulations. We first show that the identifiability of causal effects occurs if and only if the coarse subpopulations partition the whole population. We then propose a principle, called minimum variance principle, which says that the estimator possessing the minimum variance is preferred, in dealing with the stratification and the estimation of the causal effects. The simulation results with the detail programming and a practical example demonstrate that it is a feasible and reasonable way to achieve our goals.

Computer Simulation↗

Stratification of summary statistic tests according to missing data patterns.

Summary statistics, such as slope or area under the time-response curve, reduce the dimensionality of repeated measures data and can thereby simplify the comparison of groups in longitudinal studies. Since summary statistic distributions vary according to the amount, timing, and type of any missingness that occurs, one must choose between analysing the data unconditionally or conditionally on the missingness patterns. This paper uses simulations to compare such unstratified and stratified summary statistic analyses with respect to their size and power under models that allow for both non-informative and informative missingness mechanisms. Of particular interest is the robustness of these methods to violations of the assumptions that one must make if they are to have proper test size. It is found that stratification of the analysis tends to result in an increase of power, and improves the robustness to violations of missing data assumptions.

Computer Simulation↗

The LEP gene and age of menarche: maternal age as a potential cause of hidden stratification in association studies.

Leptin has a powerful effect on fertility and the initiation of puberty in addition to its effect on obesity. It has been suggested that that in times of fasting, infertility induced by low leptin levels protect the female from the energy demands of pregnancy. Despite this there have been no studies of the potential role of LEP gene variants on the age of onset of menarche. We genotyped 183 non-Hispanic Caucasian adult females at the LEP D7S1875 dinucleotide repeat polymorphism. The alleles were placed into three genotypes, <208/<208 bp, heterozygotes, and > or =208/> or =208 bp. A hierarchical ANOVA was performed with age of menarche as the dependent variable and LEP(1875) genotypes and maternal age (age of the mothers at birth of the subject) as independent variables. There was a significant (P </= 0.006) interaction of LEP(1875) x maternal age but neither independent variable was significant by itself. This was due to an "association crossover effect" in which the LEP(1875) by age of menarche effects were in opposite directions for those with a maternal age of <30 years compared to those with a maternal age of > or =30 years. If maternal age effects prove to be generalized, failure to take them into consideration could provide a source of hidden stratification that could significantly alter the replication of association studies.

Adult↗

Renal-cell carcinoma with intracaval neoplastic extension: stratification and surgical technique.

Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.

Aged↗

Stratification for elective laparoscopic cholecystectomy.

BACKGROUND: In a former retrospective study in our clinic, an improvement in patient care was observed after the introduction of laparoscopic cholecystectomy. The aim of this study was to verify whether this improvement could be maintained or even be further improved. METHODS: Retrospective evaluation of all patients who underwent an elective cholecystectomy due to symptomatic cholelithiasis. We compared the results of 1992, the year of the introduction of laparoscopic cholecystectomy with 1993, the year that laparoscopic cholecystectomy became standard procedure. Also we compared specialized with general surgeons. RESULTS: In comparison with 1992 more elective cholecystectomies were performed in 1993 (162 vs 211). In 1993 there were more primary laparoscopic procedures (86 vs 93%) but due to an increase in conversion rate in 1993 (2.5 vs 10%) the overall number of open procedures remained comparable (17 vs 16%). In 1993 there was an increase in cholecystectomies by general surgeons (56 vs 72%). The general surgeons almost doubled their conversion rate in 1993 (6 vs 13%) while that of the specialized surgeons remained comparable (0 vs 2%). Morbidity and mortality remained comparable between 1992 and 1993 and between specialized and general surgeons. CONCLUSIONS: The quality of patient care has not significantly been altered. An improvement could be made if more laparoscopic operations were performed by specialized surgeons, but this would negatively interfere with the working methods of a general hospital. Therefore we suggest stratification: Certain patients, as high-risk patients, preferably should be operated on by specialized surgeons, while routine operations could be performed by general surgeons.

Cholecystectomy, Laparoscopic↗

Stratification in perception and action.

This paper discusses the concept of stratification, in the sense of levels of analysis and levels of control, in relation to human perception and performance. It is contended that functional analysis is the proper level of analysis for the domain of perception and action. This is illustrated by means of models of cognitive energetics and motor control. The functional level of analysis can be situated in between the level of symbolic representations and the level of neurophysiological mechanisms. It is also argued that the concept of levels of control provides a way of integrating or relating ecological and information-processing approaches to psychology, in the sense that ecological psychology is concerned with lower and more peripheral levels of control (coordinative structures). Finally, some remarks are made on the relation between cognition and perception and action, drawing on Piaget, and it is proposed that the concept of schema is more appropriate for the domain of perception and action than is the notion of symbolic representations.

Attention↗

Proposed definitions for diagnosis, severity scoring, stratification, and outcome for trials on intraabdominal infection. Joint Working Party of SIS North America and Europe.

Analysis of the experience with scientific studies on patients with secondary intraabdominal infection has revealed that problems of interpretation and comparability between studies exist as they relate to variable diagnostic criteria, unmeasured severity of disease, and unclear outcome measures. A consistent system of definitions has been developed to address these deficiencies. Intraabdominal infection is defined as clinical peritonitis requiring both operative and microbiological confirmation for proof of infection. The APACHE II system is proposed for grading the severity of the infection and for stratification of patient risk of mortality. Mortality and time until death, on one hand, and recovery and time until recovery, on the other, are proposed as the main outcome measures, both being independently and positively defined. It is anticipated that this system of minimum rules will produce studies that can be compared, hence, accelerating knowledge and understanding about intraabdominal infection and its best treatment.

Abscess↗

Seasonality of birth in schizophrenia. An insufficient stratification of control population?

The seasonality of birth in 142 schizophrenics from Barcelona (Spain) has been studied, showing a pattern similar to that described by other authors, with a maximum in winter. If sample is compared with the local general population there are significant differences, but these disappear when the comparison is made with a control population properly stratified by age, sex, place of birth, place of residence and social status. The same results are obtained using statistical methods suggested by other authors. The seasonality pattern usually obtained in schizophrenia could be due to a selective stratification of the ill population based on variables that might or might not be related to illness.

Adolescent↗

Stratification in the gallbladder during intravenous cholangiography.

The stratification (layering) phenomenon in the gallbladder is a source of errors in interpretation of intravenous cholangiography. It may mimic stones that do not exist or conceal stones that do. To avoid false-positive or false-negative interpretations, it is suggested that delayed films be taken at 4 hours in cases which demonstrate a layering phenomenon. By this time, a normal gallbladder will be homogeneously opacified and a diseased one will reveal its stones. Horizontal beam roentgenograms are mandatory for complete evaluation.

Adult↗

Risk group stratification and prognostic factors in papillary carcinoma of thyroid.

BACKGROUND: Our understanding of the natural history of differentiated thyroid carcinoma has improved with the definition of prognostic factors. These prognostic factors have helped us identify patients in various risk groups. METHODS: A retrospective review of a consecutive series of 810 previously untreated patients with papillary carcinoma of the thyroid was undertaken to analyze the prognostic factors and risk groups. There were 403 patients in the low-risk group, 313 in the intermediate group, and 94 classified in the high-risk group. RESULTS: With a median follow-up of 20 years, 99% survival was achieved in the low-risk group, whereas only 43% survived in the high-risk group. The intermediate-risk group had a 20-year survival of 83%. The favorable prognostic factors included female sex, young age, absence of distant metastases and extrathyroidal extension of the disease, size < 4 cm, and low-grade histology. Focality, presence of lymph node metastasis, and pure papillary or mixed variant had no statistical significance on prognosis. CONCLUSIONS: Based on various prognostic factors, low-, intermediate-, and high-risk groups are identified. Patients in the low-risk group have excellent survival (99%). Appropriate selection of surgical and adjuvant treatment should therefore be used based on prognostic factors and risk group stratification.

Age Factors↗

Squamous cell metaplasia in the human lung: molecular characteristics of epithelial stratification.

Squamous cell metaplasia (SCM) is a frequent epithelial alteration of the human tracheobronchial mucosa. This review pays particular attention to the fact that SCM can mimic esophageal, and in some instances even skin-type differentiation, showing striking similarities not only in morphology but also in terms of gene expression. Therefore, characterization of this dynamic process lends insight into the process of stratification, squamous cell formation, and "keratinization" in a pathologically relevant in vivo situation in man. First, the concept of metaplasia is presented with certain historical viewpoints on histogenesis. Then, the morphological characteristics of normal bronchial epithelium are compared with the altered phenotype of cells in SCM. These changes are described as a disturbance of the finely tuned balance of differentiation and proliferation through the action of a variety of extrinsic and intrinsic factors. Molecular aspects of altered cell/cell and cell/extracellular matrix interactions in stratified compared with single-layered epithelia are discussed with reference to SCM in the lung. Intracellular organizational and compositional changes are then summarized with special emphasis on the differential distribution of the cytokeratin (CK) polypeptides. Finally, the still unresolved problems of the histogenetic relationships between normal bronchial mucosa, SCM, and pulmonary neoplasms are addressed. As these questions remain open, examples for detection of well defined "markers" are provided that may be employed as objective criteria for determining clinically important cellular differentiation features.

Cell Differentiation↗

Risk stratification of patients with coronary artery disease and left ventricular dysfunction by exercise radionuclide angiography and exercise electrocardiography.

BACKGROUND: The results of multicenter trials indicate that patients with left ventricular dysfunction and either three-vessel or left main coronary artery disease have improved prognosis when treated surgically. OBJECTIVE: As part of a larger evaluation and follow-up study of coronary artery disease, the objective of this investigation was to determine whether exercise radionuclide angiography can be used, in patients with mild symptoms of coronary artery disease and left ventricular dysfunction at rest, to identify patients with three-vessel or left main coronary artery disease. METHODS AND RESULTS: Eighty-four consecutive patients were studied with angiographically defined coronary artery disease in whom left ventricular ejection fraction at rest ranged from 20% to 40%. Patients underwent exercise electrocardiography, rest and exercise radionuclide angiography, and 24-hour electrocardiographic monitoring. There were 22 patients with one-vessel, 31 with two-vessel, 27 with three-vessel, and four with left main coronary artery disease. All but four patients had a documented history of myocardial infarction. By univariate analysis, the following parameters were related to the anatomic severity of coronary artery disease: magnitude of ST segment depression with exercise (p < 0.001), magnitude of change in ejection fraction with exercise (p < 0.005), and occurrence of angina during exercise (p < 0.005). However, because of the extensive overlap among anatomic subgroups, no single factor had both a satisfactory sensitivity and a satisfactory specificity in identifying patients with three-vessel and left main coronary artery disease. Multivariate stepwise regression analysis also failed to predict three-vessel or left main coronary artery disease satisfactorily (sensitivity 73% and specificity 73%; positive predictive accuracy 59% and negative predictive accuracy 83%). Nonetheless, this multivariate analysis provided important prognostic information. During medical therapy (mean follow-up 56 months), the patients with a high likelihood of three-vessel or left main coronary artery disease had a greater risk of death or reinfarction than had patients with a low likelihood (p < 0.05). These functional data were better than coronary anatomy alone in providing risk stratification. Four of six patients with two-vessel disease who died were classified incorrectly by the multivariate analysis in the high-likelihood group for three-vessel or left main coronary artery disease, but classified correctly as being at high risk; whereas none of the patients with three-vessel disease who were misclassified in the low-likelihood group died during medical therapy. CONCLUSION: Although exercise radionuclide angiography in patients with minimal symptoms of coronary artery disease and left ventricular dysfunction is not precise in predicting three-vessel or left main coronary artery disease, it provides important functional information regarding subsequent prognosis during medical therapy.

Adult↗

The stratification of cardiac surgical procedures according to use of blood products: a retrospective analysis of 1480 cases.

The use of blood products in 1480 consecutive cases of adult cardiac surgical procedures over a period of 15 mth was studied retrospectively using the database of the Department of Anaesthesia of the Institut de Cardiologie de Montréal. Use of blood products was compared in patients having (1) coronary artery bypass grafting, (2) valvular surgery, (3) or a combination of 1 and 2. First operations were compared with reoperations. Overall, the use of homologous blood products was greatest in patients of Group 3, intermediate in patients of Group 2, and smallest in patients of Group 1. Reoperations were associated with an increase in intraoperative transfusion of packed red blood cells, but postoperative chest drainage was similar to first operations. When all blood products (packed red blood cells, fresh frozen plasma and platelets) were taken into consideration, patients undergoing primary CABG or valve surgery were the least exposed to homologous blood donors (five and six units transfused respectively). Repeat CABG was associated with an intermediate exposure to homologous blood products (eight units). Finally, primary and repeat combined procedures, and repeat valve surgery were associated with the greatest exposure to foreign blood products (10, 13 and 10 units respectively). The data presented in this study provide a rational basis for stratification of procedures according to the expected use of blood products, particularly in view of future studies which may be planned to examine the efficiency of blood conservation strategies.

Aged↗

Genetic and epigenetic biomarkers in cancer : improving diagnosis, risk assessment, and disease stratification.

Gene expression patterns change during the initiation, progression, and development of cancer, as a result of both genetic and epigenetic mechanisms. Genetic changes arise due to irreversible changes in the nucleotide sequence, whereas epigenetic changes occur due to changes in chromatin conformation, histone acetylation, and methylation of the CpG islands located primarily in the promoter region of a gene. Both genetic and epigenetic markers can potentially be utilized to identify different stages of tumor development. Several such markers exhibit high sensitivity and specificity for different tumor types and can be assayed in biofluids and other specimens collected by noninvasive technologies. In spite of the availability of large numbers of diagnostic markers, only a few have been clinically validated so far. The current status and the challenges in the field of genetic and epigenetic markers in cancer diagnosis, risk assessment, and disease stratification are discussed.

Biomarkers, Tumor↗

[Acute coronary syndromes: an update. II. Coronary revascularization and risk stratification].

UNLABELLED: CORONARY REVASCULARIZATION: PTCA in patients with refractory unstable angina is associated with a substantial risk of the following complications: death, myocardial infarction, need for emergency surgery, and restenosis. The introduction of intracoronary stents, however, has improved both short-term and long-term outcomes. The newer adjunctive pharmacologic therapies enhance even further the benefits associated with the use of stents. The decision regarding the specific revascularization procedure to be used (e.g., CABG, PTCA, stent placement, or atherectomy) is based on the coronary anatomy, the left ventricular function, the experience of the medical and surgical personnel, the presence or absence of coexisting illnesses, and the preferences of both the patient and the physician. RISK STRATIFICATION: Among patients with unstable angina or non-Q-wave myocardial infarction, there is an increased risk of death within 6 weeks in those with elevated troponin I levels and the risk of death continues to increase as the troponin level increases. Reversible ST segment depression is associated with an increase by a factor of 3-6 in the likelihood of death, myocardial infarction, ischemia at rest, or provocable ischemia during a test to stratify risk. Exercise or pharmacologic stress testing provides important information about a patient's risk. Although the conditions of the majority of patients with unstable angina will stabilize with effective antiischemic medications, approximately 50-60% of such patients will require coronary angiography and revascularization because of the "failure" of medical therapy. High-risk patients are those who have had angina at rest, prolonged angina, or persistent angina with dynamic ST segment changes or hemodynamic instability, and they urgently require simultaneous invasive evaluation and treatment. Medical therapy should be adjusted rapidly to relieve manifestations of ischemia and should include antiplatelet therapy (aspirin, or ticlopidine or clopidogrel if aspirin is contraindicated), antithrombotic therapy (unfractionated heparin or low-molecular-weight heparin), beta-blockers, nitrates, and possibly calcium-channel blockers. Early administration of glycoprotein IIb/IIIa inhibitors may be particularly important, especially in high-risk patients with positive troponin tests or those in whom implantation of coronary stents is anticipated.

Acute Disease↗

[Acute coronary syndrome and inflammation. Biomarkers for diagnostics and risk stratification].

Inflammation plays a pivotal role in atherosclerosis and coronary heart disease. Inflammatory processes of the coronary arterial wall are involved in plaque formation, progression and, finally, plaque instability consecutively leading to the clinical manifestations of stable coronary artery disease or acute coronary syndromes (unstable angina, non-ST elevation and ST elevation myocardial infarction). Acute coronary syndromes result from plaque rupture or erosion leading to local thrombus formation with consecutive necrosis of myocytes due to ischemia, which is associated with widespread and diffuse pancoronary and panmyocardial inflammation. Accordingly, markers of myocardial necrosis (e. g., cardiac troponins) do have crucial diagnostic and prognostic value. In case of troponin-negative acute coronary syndromes, however, markers of inflammation emerged as potentially useful tools for risk stratification. C-reactive protein has been shown to serve as a powerful predictor of future cardiovascular events following acute coronary syndromes, even if troponins are not (yet) positive. Moreover, a variety of pro- (soluble CD40 ligand, placental growth factor, interleukin-6, pregnancy-associated plasma protein A, myeloperoxidase, monocyte chemoattractant protein-1) and anti-inflammatory markers (interleukin-10, activin A) have been suggested to provide relevant prognostic information in patients with acute coronary syndrome. However, the clinical utility of these novel markers has not been established so far.

Acute Disease↗

[Acute coronary syndrome--better risk stratification by determination of inflammatory parameters?].

BACKGROUND: In the past years coronary atherosclerosis and plaque rupture have been characterized not only as a problem of growth of smooth vascular cells, of activated thrombocytes and coagulation but also of inflammation. PARAMETERS OF INFLAMMATION: Several studies have demonstrated the importance of C-reactive protein as a marker for cardiovascular complications. Also interleukin-6, tumor necrosis factor-alpha and adhesion molecules are discussed as predictors of a poor prognosis in patients with acute coronary syndromes. RISK STRATIFICATION: A positive troponin T test is correlated with an increased rate of early complications; thus, these patients benefit from an aggressive therapy with GP IIb/IIIa receptor antagonists and acute coronary intervention. The C-reactive protein is predictive for late complications such as restenosis, reinfarction and death due to cardiac events; these patients benefit from close controls and from an anti-inflammatory therapy with acetylsalicyclic acid and statins.

C-Reactive Protein↗

CT-guided percutaneous drainage of intra-abdominal abscesses: APACHE III score stratification of 1-year results. Acute Physiology, Age, Chronic Health Evaluation.

Our objective was to evaluate the clinical success rates of percutaneously drained intra-abdominal abscesses using a risk stratification score for severely ill patients (APACHE III; Acute Physiology, Age, Chronic Health Evaluation). In 75 patients CT-guided percutaneous abscess drainage was performed to treat intra-abdominal abscesses. The clinical success rate based on a 1-year follow-up was correlated with abscess etiology, size, and structure, as well as with the initial APACHE III score. Clinical success, i.e., the complete removal of the abscess without surgical treatment, was observed in 62 of 75 patients (83%). Abscess size (<200 cm(3)) and abscesses with a simple structure correlated with higher clinical success rates. Patients presenting with APACHE III scores below 30 were treated by percutaneous abscess drainages (PAD) alone significantly more often than patients presenting with higher APACHE scores. The percutaneous drainage of intra-abdominal abscesses shows good long-term results as long as abscesses are singular, small (<200 cm(3)), and located in well accessible regions in combination with low APACHE scores (<30).

Abdominal Abscess↗