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DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.

Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of GJB2 in a cohort of hearing impaired patients and a multi-ethnic control group is reported. Among 610 hearing impaired cases, 43 DNA sequence variations were identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms, 3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and 7 novel variants (G12C, N14D, V63A, T86M, L132V, D159, 592_600delinsCAGTGTTCATGACATTC). Sixteen non-coding sequence variations were also identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13 novel variants. A diagnosis of GJB2-associated hearing loss was confirmed for 63 cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases carrying novel or unclassified variants (1.8 %) and 18 cases carrying the controversial V37I variant were identified (3%). In addition, 294 control subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence variations in the coding region of GJB2 were identified among controls including 2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1 controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence variations were identified among controls in the non-coding regions in and around GJB2 exon 2. Of particular interest among controls were the variability in carrier rates and ethnic stratification of alleles, and the complex genotypes among Asians, 47% of whom carried two to four sequence variations in the coding region of GJB2. These data provide new information about carrier rates for GJB2-based hearing loss in various ethnic groups and contribute to evaluation of the pathogenicity of the controversial V37I variant.

Alleles↗

Stratificational relationship among the main nerves from the dorsal division of the sacral plexus and the innervation of the piriformis.

In order to comprehend more completely the morphology of the nerves to the piriformis, it is necessary to obtain a detailed understanding of the relationship of the origin and the course of these nerves from the dorsal division of the sacral plexus, with reference to the superior and inferior gluteal nerves. Twelve of seven human pelvic halves were carefully dissected in order to examine the origins of the nerves from the dorsal division of the sacral plexus. Six of these pelvic halves were further dissected under a stereomicroscope to examine the nerves to the piriformis. 1. The origin of the superior gluteal nerve was more proximal and dorsal in the sacral plexus than that of the inferior gluteal nerve. 2. The superior gluteal nerve consisted of a thick cranial part and a thin caudal part; the former continued as the inferior branch of the nerve, and the latter, the superior branch. The cranial and caudal parts crossed before reaching the glutei medius and minimus. 3. The nerves to the piriformis arose from three main nerves from the dorsal division of the sacral plexus: 1) the caudalmost root of the superior gluteal nerve, 2) the caudal roots of the inferior gluteal nerve and 3) the common peroneal nerve. Considering the stratificational relationship among the main nerves from the dorsal division of the sacral plexus, the piriformis appears to be composed of parts from different muscle layers.

Buttocks↗

Mortality and perforated peptic ulcer: a case for risk stratification in elderly patients.

In a consecutive series of 284 patients with a perforated peptic ulcer (229 pyloroduodenal, 55 gastric) there was a 26 per cent hospital mortality rate, and patients aged greater than or equal to 70 years (n = 176) had a significantly higher mortality rate (34 per cent) than patients aged less than 70 years (14 per cent, P less than 0.001). Multiple clinical variables were significantly more common in the elderly group of patients (65 per cent), in those having non-steroidal anti-inflammatory drugs or steroid therapy (56 per cent), in patients where there is an absence of a previous dyspeptic history (69 per cent), and when risk factors such as delayed presentation (33 per cent) and the presence of shock on admission to hospital (27 per cent) are present. Definitive operations (vagotomy or gastrectomy) had an increased mortality rate in the elderly (P = 0.018). Risk scores based upon the presence of shock, delayed presentation or concurrent medical illness could have predicted 87 per cent of postoperative deaths in elderly subjects, and it is suggested that risk stratification and greater caution in the use of definitive operations for perforated ulcer may result in a reduction in the high mortality rate in elderly subjects.

Adult↗

The role of cardiac troponin T and other new biochemical markers in evaluation and risk stratification of patients with acute chest pain syndromes.

BACKGROUND AND HYPOTHESIS: Increased serum creatinine kinase (CK) and CK-MB enzyme levels have been used for years to detect myocardial infarction (MI). However, serum myoglobin and CK-MB mass or protein levels may indicate MI earlier; cardiac troponin T is the most specific marker of myocardial injury and it can detect even minor myocardial necrosis. The diagnostic and prognostic utility of the traditional and new markers of cardiac injury in the emergency evaluation of patients with acute chest pain syndromes were therefore compared. METHODS: One hundred and fifteen consecutive patients with an acute coronary syndrome, and 64 controls recruited during the same period, were examined. The time elapsed from onset of symptoms to blood collection was recorded. Cardiac markers were measured in specimens collected upon arrival (0 h), and 2 and 5-9 h, and later in cases of longer observation. The major cardiac events occurring up to 40 months after the index examination were recorded. RESULTS: cTnT levels provided unique information: they were the most specific indicators of myocardial damage and identified unstable angina patients at high risk of future major events. Up to 6 h after the onset of chest pain, the new markers were elevated more frequently than the traditional ones and permitted earlier MI recognition. The worst prognosis (nonfatal myocardial infarction or death) was noted in subjects with chest pain at rest within 48 h before the index examination and elevated cTnT levels. CONCLUSIONS: The new markers, particularly cardiac troponin T, offer considerable advantages and they should be more widely used in the diagnosis and risk stratification of acute coronary syndromes.

Adult↗

Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials.

BACKGROUND: The objective of the current study was to develop an algorithm to predict progression to metastases after radical nephrectomy for patients with clinically localized renal cell carcinoma (RCC) to allow stratification of patients for potential adjuvant therapy trials. METHODS: The authors identified 1671 sporadic patients with clinically localized, unilateral clear cell RCC who underwent radical nephrectomy between 1970 and 2000. The clinical features examined included age, gender, smoking history, recent onset hypertension, performance status, and presenting symptoms. The pathologic features examined included surgical margins, tumor stage, regional lymph node status, tumor size, nuclear grade, histologic tumor necrosis, sarcomatoid component, cystic architecture, and multifocality. Metastases free survival was estimated using the Kaplan-Meier method. A multivariate Cox proportional hazards regression model was fit to determine associations between the clinical and pathologic features and distant metastases. RESULTS: The median follow-up was 5.4 years (range, 0-31 years). Metastases occurred in 479 patients at a median of 1.3 years (range, 0-25 years) after nephrectomy. The estimated metastases free survival rates were 86.9% at 1 year, 77.8% at 3 years, 74.1% at 5 years, 70.8% at 7 years, and 67.1% at 10 years. Multivariate analysis showed that the following features were associated with progression to metastases: tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis (P < 0.001 for all). CONCLUSIONS: In patients with clear cell RCC, tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis showed statistically significant associations with progression to metastatic RCC. The authors present a scoring algorithm based on these features that can be used to predict disease progression after patients undergo radical nephrectomy for clinically localized clear cell RCC. Cancer 2003;97:1663-71.

Adenocarcinoma, Clear Cell↗

Recursive partitioning for risk stratification in men undergoing repeat prostate biopsies.

BACKGROUND: The current study was performed to identify risk factors and risk groups for carcinoma detection in men undergoing repeat prostate biopsies. METHODS: The medical records of all men who had a negative initial prostate biopsy and underwent at least one repeat biopsy between 1992 and 2003 were reviewed to extract age, race, family history of prostate carcinoma, body mass index, referral indication, all prostate-specific antigen (PSA) values, digital rectal examination, PSA density (PSAD), the presence of a hypoechoic lesion, and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy. Risk factors for a subsequent diagnosis of prostate carcinoma were identified using the log-rank test and a stepwise, stratified Cox regression model. Based on the risk factors identified by Cox regression analysis, recursive partitioning was further used for risk stratification. RESULTS: A total of 373 patients underwent 975 biopsy procedures. During a median follow-up of 37.0 months, prostate carcinoma was detected in 107 of 373 patients (28.9%). Independent predictors of a positive biopsy (P < 0.05) were PSA doubling time (PSADT), PSAD, referral indication, the presence of HGPIN, patient age, and family history of prostate carcinoma. Recursive partitioning identified 4 distinct risk groups that were characterized by their PSADT and PSAD and the presence of HGPIN and had estimated 2-year and 5-year carcinoma detection rates of 3 +/- 1% and 21 +/- 4%, 28 +/- 5% and 40 +/- 7%, 22 +/- 6% and 58 +/- 8%, and 66 +/- 9% and 100%, respectively. CONCLUSIONS: The authors identified a series of independent risk factors for prostate carcinoma detection after an initial negative prostate biopsy and characterized clinically meaningful and distinct patient risk groups. Despite a negative initial biopsy, patients with high-risk features remain at risk for the detection of prostate carcinoma.

Adult↗

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans↗

Polyaxonal amacrine cells of rabbit retina: morphology and stratification of PA1 cells.

Polyaxonal amacrine cells are a new class of amacrine cell bearing one to six branching, axon-like processes, closely resembling the axons of Golgi type II cells found elsewhere in the central nervous system. Of the four types of polyaxonal amacrine cell that we have recognized in rabbit retina, three have been described previously in brief communications, and one is the subject of this paper. Type 1 polyaxonal (PA1) amacrine cells have larger cell bodies than most amacrine cells in Golgi preparations, averaging about 13 microns in diameter. These are typically positioned interstitially in the middle of the inner plexiform layer (IPL), although some are also found in the amacrine and ganglion cell layers. Axons and dendrites are broadly stratified in the middle of the IPL, in the vicinity of the a/b sublaminar border. Sparsely branching dendrites have a conventional appearance, branching at a narrow angle, and giving rise to smaller daughter branches, which taper gradually toward their termination. An unusual feature of the dendrites is the zig-zag course of some terminal branches. Clusters of small, pedunculated spines are common on proximal dendrites, and spines are virtually absent on axons. Axons emerge from proximal dendrites within 50 microns of the soma, and more rarely from the soma, in a tapering initial segment, commonly interrupted by one or two large swellings. Subsequent branching is at a wide angle, and the fine caliber is maintained in the transition from parent to daughter branches. The uniform thickness of the axonal branches is interrupted at intervals by boutons en passant. Although the extent of the dendritic tree is large, exceeding 500 microns in radial extent from the cell body, for cells a few millimeters distant from the visual streak, the axonal tree is much larger, and its radial extent is measured in millimeters. PA1 amacrine cells are believed to be polarized in their functional organization, with a primarily recipient dendritic tree and a primarily transmissive axonal tree. PA1 amacrine cells co-stratify with nab cone bipolar cells and with certain small tufted amacrine and ganglion cells at the a/b sublaminar border. The co-stratification of both axons and dendrites at the a/b sublaminar border of the IPL suggests that PA1 amacrine cells are important modulators of neural activity in the middle of the IPL, affecting both ON and OFF responses, and perhaps ON-OFF cells selectively.

Animals↗

Large retinal ganglion cells in the channel catfish (Ictalurus punctatus): three types with distinct dendritic stratification patterns form similar but independent mosaics.

Retinal ganglion cells in the channel catfish (Ictalurus punctatus) were retrogradely labelled, and those with the largest somata and thickest primary dendrites were categorized by their levels of dendritic stratification. Three types were found, each forming a mosaic making up approximately 1% of the ganglion cell population. Using a system based on established sublaminar terminology, we call these the alpha-a (alpha a), alpha-b (alpha b), and alpha-c (alpha c) ganglion cell mosaics. Cells of the alpha a mosaic had large, sparsely branched trees in sublamina a at 10-30% of the depth of the inner plexiform layer (IPL), sclerad to those of all other large ganglion cells. Some alpha a somata were displaced into the IPL or inner nuclear layer (INL) but belonged to the same mosaic as their orthotopic counterparts. Cells of the alpha b mosaic had dendrites that branched a little more and arborized in sublamina b at 50-60% of the IPL depth. Many also sent fine branches into sublamina a, and some were fully bistratified in a and b. The alpha c cells arborized in the most vitread sublamina, sublamina c, at 80-95% of the IPL depth. The soma areas of the three types in the largest retina studied ranged between 139 microns 2 and 670 microns 2 with significant differences in the order alpha a > alpha c > or = alpha b. Analyses based on nearest-neighbour distance (NND) and on spatial auto- and cross-correlograms showed that each mosaic was statistically regular and independent of the others. Mosaic spacings were similar for each type, giving mean NNDs of 242-279 microns in the largest retina and 153-159 microns in a smaller one. Correspondences between these mosaics, previously defined large ganglion cell types in catfish, and other mosaic-forming large ganglion cells in fish and frogs are discussed along with their implications for neuronal classification, function, development, and evolution.

Animals↗

Thrombus Metabolism-Based Molecular Subtyping for Prognostic Risk Stratification in Acute Ischemic Stroke: A Preliminary Study.

AIMS: To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS: Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS-LVO using ultra-performance coupled liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. RESULTS: Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short-term (7-day &#x2206;NIHSS) and long-term (90-day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short-term and long-term outcomes. A six-metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90-day outcomes. CONCLUSION: This preliminary exploratory study identifies two metabolically distinct thrombus molecular subtypes with clinical implications in anterior circulation AIS-LVO, providing a novel basis for risk stratification and personalized secondary prevention and warrants further investigation.

Humans↗

Immunophenotyping is an independent factor for risk stratification in AML.

BACKGROUND: Chromosomal abnormalities are one of the most important prognostic factors in acute myeloid leukemia (AML). However, only a limited number of patients have such informative chromosomal abnormalities. The prognostic value of immunophenotyping in this disease is still unclear. METHODS: Seven hundred and eighty-three newly diagnosed AML patients treated in the German SHG-AML trials in 1991 and 1996 were analyzed with a panel of 33 antibodies. Expression was correlated to overall survival, complete remission-rate, and complete remission duration, and tested in a multivariate analysis including other clinical and biological markers. RESULTS: With a median follow-up of 4.3 years, patients with AML blasts negative for CD9, CD11b, CD13, CD34, and CD41, or positive for CD15, CD33, CD38, CD64, and MPO had superior overall survival. This effect was associated with a significantly higher complete remission rate (CD13, CD34, CD41, and CD64) or a longer complete remission duration (CD9, CD11b, and CD64). Cox-regression analysis, including cytogenetic, morphologic, and biologic parameters showed CD9, CD13, CD34, and CD64 as independent factors for overall survival. These markers were used for a prognostic score. Patients were pooled in three groups with highly significant differences of overall survival. The prognostic relevance of this score was confirmed in patients with normal karyotype and/or in younger patients </= 60 years. CONCLUSIONS: Immunophenotyping is not only helpful for diagnosis but is of independent significance for prognosis, and may be useful for risk stratification in AML patients.

Acute Disease↗

Stratification techniques to explore genotype environment interactions.

Linkage analysis was performed on the GAW11 Problem 2 data set using stratification to explore the effects of the environmental risk factors and the differences between mild and severe phenotypes. Analysis of the four study populations stratified by the two risk factors identified regions on chromosomes 3 and 5 with significant evidence for linkage. Other loci were sought by removing families consistent with linkage to the chromosome 3 locus. Our studies identified a locus on chromosome 3 (markers 43-46) associated with the mild phenotype in the presence of risk factor 1 and with the severe phenotype independent of risk factor 1. This suggests that distinct allelic variants at the chromosome 3 locus may cause different forms of disease. The locus identified on chromosome 5 (markers 36-39) was linked to the severe phenotype, but exposure to factor 1 or 2 may have a protective effect. The regions on chromosomes 3 and 5 appeared to have independent roles in disease etiology. Evidence for two loci on chromosome 1 linked to the mild form was found. The methods successfully identified linkages and interaction consistent with the generating model.

Environment↗

Evaluating bias due to population stratification in case-control association studies of admixed populations.

The potential for bias from population stratification (PS) has raised concerns about case-control studies involving admixed ethnicities. We evaluated the potential bias due to PS in relating a binary outcome with a candidate gene under simulated settings where study populations consist of multiple ethnicities. Disease risks were assigned within the range of prostate cancer rates of African Americans reported in SEER registries assuming k=2, 5, or 10 admixed ethnicities. Genotype frequencies were considered in the range of 5-95%. Under a model assuming no genotype effect on disease (odds ratio (OR)=1), the range of observed OR estimates ignoring ethnicity was 0.64-1.55 for k=2, 0.72-1.33 for k=5, and 0.81-1.22 for k=10. When genotype effect on disease was modeled to be OR=2, the ranges of observed OR estimates were 1.28-3.09, 1.43-2.65, and 1.62-2.42 for k=2, 5, and 10 ethnicities, respectively. Our results indicate that the magnitude of bias is small unless extreme differences exist in genotype frequency. Bias due to PS decreases as the number of admixed ethnicities increases. The biases are bounded by the minimum and maximum of all pairwise baseline disease odds ratios across ethnicities. Therefore, bias due to PS alone may be small when baseline risk differences are small within major categories of admixed ethnicity, such as African Americans.

Black or African American↗

Hierarchical modeling of the relation between sequence variants and a quantitative trait: addressing multiple comparison and population stratification issues.

When analyzing the relation between genetic sequence information and disease traits, false-positive associations can arise due to multiple comparisons and population stratification. In an attempt to address these issues, we incorporate into a conventional analytic model higher-level--or "prior"--models that use additional information to improve estimates while allowing for differing population structures. We apply this hierarchical model to simulated data from the Genetic Analysis Workshop 12. We focus on the effects of common candidate gene sequence variants on quantitative risk factor 5 (Q5) levels. In particular, we compare the regression coefficients (and 95% confidence intervals) obtained from conventional (one-stage) analyses versus the corresponding results from the hierarchical analyses. When examining either the marry-ins or all subjects in the general and isolate populations, the conventional model detected numerous sites in candidate genes 1-5 and 7 that had statistically significant regression coefficients (alpha level = 0.05). In contrast, our hierarchical model primarily only detected associations for variants in candidate gene 2, which is the casual gene for Q5.

Chromosome Mapping↗

Centralizing the non-central chi-square: A new method to correct for population stratification in genetic case-control association studies.

We present a new method, the delta-centralization (DC) method, to correct for population stratification (PS) in case-control association studies. DC works well even when there is a lot of confounding due to PS. The latter causes overdispersion in the usual chi-square statistics which then have non-central chi-square distributions. Other methods approach the noncentrality indirectly, but we deal with it directly, by estimating the non-centrality parameter tau itself. Specifically: (1) We define a quantity delta, a function of the relevant subpopulation parameters. We show that, for relatively large samples, delta exactly predicts the elevation of the false positive rate due to PS, when there is no true association between marker genotype and disease. (This quantity delta is quite different from Wright's F(ST) and can be large even when F(ST) is small.) (2) We show how to estimate delta, using a panel of unlinked "neutral" loci. (3) We then show that delta2 corresponds to tau the noncentrality parameter of the chi-square distribution. Thus, we can centralize the chi-square using our estimate of 6; this is the DC method. (4) We demonstrate, via computer simulations, that DC works well with as few as 25-30 unlinked markers, where the markers are chosen to have allele frequencies reasonably close (within +/- .1) to those at the test locus. (5) We compare DC with genomic control and show that where as the latter becomes overconservative when there is considerable confounding due to PS (i.e. when delta is large), DC performs well for all values of delta.

Bayes Theorem↗

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5&#x2009;months, 5-year PFS and OS for the whole cohort (n&#x2009;=&#x2009;86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR&#x2009;=&#x2009;3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR&#x2009;=&#x2009;4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n&#x2009;=&#x2009;59; 89.7%-58.3%). OS differed across groups (log-rank p&#x2009;=&#x2009;0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein&#x2013;Barr virus DNA↗

Dobutamine stress echocardiography for preoperative cardiac risk stratification in patients undergoing orthotopic liver transplantation.

This study attempts to evaluate the efficacy of dobutamine stress echocardiography for preoperative cardiac risk stratification in patients undergoing orthotopic liver transplantation. Two hundred twenty consecutively submitted patients were evaluated in preparation for orthotopic liver transplantation. Dobutamine stress echocardiography was performed in 80 patients with known or suspected coronary artery disease. Follow-up information was available in 40 patients in the form of cardiac catheterization and/or outcome from liver transplantation to validate the dobutamine stress echo findings. The prevalence of coronary artery disease in this cohort was 5% and was closely associated with the presence of diabetes mellitus. Dobutamine stress echocardiography, when interpreted as abnormal in the presence of wall motion abnormalities only, is associated with a sensitivity, specificity, and positive and negative predictive value of 100%. Dobutamine stress echocardiography is highly efficacious and should be the screening study of choice to detect coronary artery disease in patients undergoing orthotopic liver transplantation.

Adult↗

Stratification and weighting via the propensity score in estimation of causal treatment effects: a comparative study.

Estimation of treatment effects with causal interpretation from observational data is complicated because exposure to treatment may be confounded with subject characteristics. The propensity score, the probability of treatment exposure conditional on covariates, is the basis for two approaches to adjusting for confounding: methods based on stratification of observations by quantiles of estimated propensity scores and methods based on weighting observations by the inverse of estimated propensity scores. We review popular versions of these approaches and related methods offering improved precision, describe theoretical properties and highlight their implications for practice, and present extensive comparisons of performance that provide guidance for practical use.

Computer Simulation↗