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Results for “Bootstrap resampling”

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PubMed2003

ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis.

Breast cancer diagnosis through ultrasound tissue characterization was studied using receiver operating characteristic (ROC) analysis of combinations of acoustic features, patient age, and radiological findings. A feature fusion method was devised that operates even if only partial diagnostic data are available. The ROC methodology uses ordinal dominance theory and bootstrap resampling to evaluate A(z) and confidence intervals in simple as well as paired data analyses. The combined diagnostic feature had an A(z) of 0.96 with a confidence interval of at a significance level of 0.05. The combined features show statistically significant improvement over prebiopsy radiological findings. These results indicate that ultrasound tissue characterization, in combination with patient record and clinical findings, may greatly reduce the need to perform biopsies of benign breast lesions.

Age Factors↗

PubMed2002

Survival analysis with time-varying regression effects using a tree-based approach.

Nonproportional hazards often arise in survival analysis, as is evident in the data from the International Non-Hodgkin's Lymphoma Prognostic Factors Project. A tree-based method to handle such survival data is developed for the assessment and estimation of time-dependent regression effects under a Cox-type model. The tree method approximates the time-varying regression effects as piecewise constants and is designed to estimate change points in the regression parameters. A fast algorithm that relies on maximized score statistics is used in recursive segmentation of the time axis. Following the segmentation, a pruning algorithm with optimal properties similar to those of classification and regression trees (CART) is used to determine a sparse segmentation. Bootstrap resampling is used in correcting for overoptimism due to split point optimization. The piecewise constant model is often more suitable for clinical interpretation of the regression parameters than the more flexible spline models. The utility of the algorithm is shown on the lymphoma data, where we further develop the published International Risk Index into a time-varying risk index for non-Hodgkin's lymphoma.

Algorithms↗

PubMed2004

Three-dimensional ultrasonographic assessment of fetal lung volume as prognostic factor in isolated congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the potential of three-dimensional ultrasound to predict outcome in congenital diaphragmatic hernia. DESIGN: Prospective observational study. SETTING: Tertiary care centre. POPULATION: Twelve cases of isolated congenital diaphragmatic hernia (11 left-sided, 1 right-sided) and 109 controls. METHODS: Fetal lung volume was assessed by three-dimensional ultrasound using the technique of rotation of the multiplanar imaging. In the control fetuses, a logistic transformation was performed to correlate fetal lung volume with gestational age, and the confidence interval was obtained with a bootstrap resampling. A mathematical equation was then obtained allowing calculation of the expected fetal lung volume as a function of gestational age. In fetuses with congenital diaphragmatic hernia, the observed/expected lung volume ratio was compared with postnatal outcome. MAIN OUTCOME MEASURES: Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012. RESULTS: The expected fetal lung volume was derived from the mathematical equation: Fetal lung volume (mL) = exp (4.72/(1 + exp ((20.32 - gestational age in weeks)/6.05))). The observed/expected fetal lung volume ratio was significantly lower in the congenital diaphragmatic hernia group (median: 0.34, range: 0.16-0.66), than in the control group (median: 1.02, range: 0.62-1.97, P < 0.0001). The distribution of this ratio was significantly downshifted in the infants with congenital diaphragmatic hernia who died (median: 0.19, range: 0.18-0.66) compared with survivors (median: 0.44, range: 0.36-0.66, P= 0.04). The observed/expected fetal lung volume ratio was also correlated with the postmortem lung/body weight ratio. CONCLUSION: In isolated congenital diaphragmatic hernia, fetal lung volume measurement by three-dimensional ultrasound is a potential predictor for pulmonary hypoplasia and postnatal outcome.

Female↗

PubMed1991

Sampling strategies for toxic air contaminants.

Annual concentrations of toxic air contaminants are of primary concern from the perspective of chronic human exposure assessment and risk analysis. Despite recent advances in air quality monitoring technology, resource and technical constraints often impose limitations on the availability of a sufficient number of ambient concentration measurements for performing environmental risk analysis. Therefore, sample size limitations, representativeness of data, and uncertainties in the estimated annual mean concentration must be examined before performing quantitative risk analysis. In this paper, we discuss several factors that need to be considered in designing field-sampling programs for toxic air contaminants and in verifying compliance with environmental regulations. Specifically, we examine the behavior of SO2, TSP, and CO data as surrogates for toxic air contaminants and as examples of point source, area source, and line source-dominated pollutants, respectively, from the standpoint of sampling design. We demonstrate the use of bootstrap resampling method and normal theory in estimating the annual mean concentration and its 95% confidence bounds from limited sampling data, and illustrate the application of operating characteristic (OC) curves to determine optimum sample size and other sampling strategies. We also outline a statistical procedure, based on a one-sided t-test, that utilizes the sampled concentration data for evaluating whether a sampling site is compliance with relevant ambient guideline concentrations for toxic air contaminants.

Air Pollutants↗

PubMed1992

Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades.

The genetic diversification of foot-and-mouth disease virus (FMDV) of serotype C over a 6-decade period was studied by comparing nucleotide sequences of the capsid protein-coding regions of viruses isolated in Europe, South America, and The Philippines. Phylogenetic trees were derived for VP1 and P1 (VP1, VP2, VP3, and VP4) RNAs by using the least-squares method. Confidence intervals of the derived phylogeny (significance levels of nodes and standard deviations of branch lengths) were placed by application of the bootstrap resampling method. These procedures defined six highly significant major evolutionary lineages and a complex network of sublines for the isolates from South America. In contrast, European isolates are considerably more homogeneous, probably because of the vaccine origin of several of them. The phylogenetic analysis suggests that FMDV CGC Ger/26 (one of the earliest FMDV isolates available) belonged to an evolutionary line which is now apparently extinct. Attempts to date the origin (ancestor) of the FMDVs analyzed met with considerable uncertainty, mainly owing to the stasis noted in European viruses. Remarkably, the evolution of the capsid genes of FMDV was essentially associated with linear accumulation of silent mutations but continuous accumulation of amino acid substitutions was not observed. Thus, the antigenic variation attained by FMDV type C over 6 decades was due to fluctuations among limited combinations of amino acid residues without net accumulation of amino acid replacements over time.

Amino Acid Sequence↗

PubMed1996

A reevaluation of the higher taxonomy of viruses based on RNA polymerases.

In order to assess the validity of classifications of RNA viruses, published alignments and phylogenies of RNA-dependent RNA and DNA polymerase sequences were reevaluated by a Monte Carlo randomization procedure, bootstrap resampling, and phylogenetic signal analysis. Although clear relationships between some viral taxa were identified, overall the sequence similarities and phylogenetic signals were insufficient to support many of the proposed evolutionary groupings of RNA viruses. Likewise, no support for the common ancestry of RNA-dependent RNA polymerases and reverse transcriptases was found.

Animals↗

PubMed1997

Molecular characterization and phylogenetic analyses of a new, highly divergent simian T-cell lymphotropic virus type 1 (STLV-1marc1) in Macaca arctoides.

A serological survey of a captive colony of Asian monkeys indicated that six Macaca arctoides had antibodies to human T-cell leukemia/lymphotropic viruses (HTLV). Over a 4-year interval, sera from these animals continued to exhibit a peculiar Western blot (WB) pattern resembling an HTLV-2 pattern (p24gag reactivity of equal or greater intensity than that of p19gag and a strong reactivity to recombinant gp21) but also exhibiting, in five of six cases, a reactivity against MTA-1, an HTLV-1 gp46 peptide. PCR experiments on DNA extracted from peripheral blood mononuclear cells using HTLV-1- or HTLV-2-specific long terminal repeat, gag, pol, env, and tax primers yielded negative results. However, highly conserved primers successfully amplified three different gene segments of env, tax, and env-tax. The results of comparative sequence analysis demonstrated that STLV-1marc1 was not closely related to any known STLV-1 strain, was the most divergent strain of the HTLV-1-STLV-1 group, and lacked the ATG initiation codons corresponding to the p12 and p13 proteins of HTLV-1. Phylogenetic analyses incorporating representative strains of all known HTLV-STLV clades consistently depicted STLV-1marc1 within the HTLV-1-STLV-1 type 1 lineage, but it probably diverged early, since its position is clearly different from all known viral strains of this group and it had a bootstrap resampling value of 100%. Genetic distance estimates between STLV-1marc1 and all other type 1 viruses were of the same order of magnitude as those between STLV-2PanP and all other type 2 viruses. In light of the recent demonstration of interspecies transmission of some STLV-1 strains, our results suggest the existence in Asia of HTLV-1 strains related to this new divergent STLV-1marc1 strain, which may be derived from a common ancestor early in the evolution of the type 1 viruses and could be therefore considered a prototype of a new HTLV-STLV clade.

Animals↗

PubMed1996

Radium in drinking water and risk of bone cancer in Ontario youths: a second study and combined analysis.

OBJECTIVES: Radium induces bone sarcomas at high doses, but there is controversy about risk at low doses. A previous study in Ontario found an association between the presence of radium in birthplace water supplies and an increased risk of death from bone cancer in young people. An investigation was performed to test the findings of the previous study with an independent group of subjects for whom complete information on radium exposure would be obtained. METHODS: A population based case-control study (238 cases; 432 controls) was conducted with incident cases of bone sarcoma identified from the Ontario cancer registry. Residential histories were collected by questionnaire and water samples were obtained and analysed for radium content. RESULTS: There was an association between risk of osteosarcoma and birthplace exposures (odds ratios (ORs) and 90% confidence intervals (90% CIs) 1.77 (1.03-3.00) but not with lifetime measures of exposure. When lifetime exposure was dichotomised, the OR was 1.31 (0.76-2.24) for osteosarcoma. There was no trend with increasing exposure. Bootstrap resampling was used to simulate lifetime doses in a pooled analysis of 1293 subjects from the two Ontario studies. The ORs were 1.38 (1.08-1.73) for all sarcomas, and 1.44 (1.01-1.87) for osteosarcoma. Geometric mean doses in bone were about 26 mRad. CONCLUSIONS: An association was found between the presence of radium in birthplace water supplies and increased risk of bone sarcoma in two studies. Increased risk was present for lifetime measures of exposure, but the association was not significant, and there was no dose-response trend. Our findings are compatible with the absence of risk at low doses, but they might also reflect inadequate statistical power to measure a true risk at environmental exposure levels. If the increased risk at environmental doses is causal, risk of bone sarcoma is effectively linearly related to dose over five orders of magnitude.

Adolescent↗

PubMed2005

A prediction rule for selective screening of Chlamydia trachomatis infection.

BACKGROUND: Screening for Chlamydia trachomatis infections is aimed at the reduction of these infections and subsequent complications. Selective screening may increase the cost effectiveness of a screening programme. Few population based systematic screening programmes have been carried out and attempts to validate selective screening criteria have shown poor performance. This study describes the development of a prediction rule for estimating the risk of chlamydial infection as a basis for selective screening. METHODS: A population based chlamydia screening study was performed in the Netherlands by inviting 21,000 15-29 year old women and men in urban and rural areas for home based urine testing. Multivariable logistic regression was used to identify risk factors for chlamydial infection among 6303 sexually active participants, and the discriminative ability was measured by the area under the receiver operating characteristic curve (AUC). Internal validity was assessed with bootstrap resampling techniques. RESULTS: The prevalence of C trachomatis (CT) infection was 2.6% (95% CI 2.2 to 3.2) in women and 2.0% (95% CI 1.4 to 2.7) in men. Chlamydial infection was associated with high level of urbanisation, young age, Surinam/Antillian ethnicity, low/intermediate education, multiple lifetime partners, a new contact in the previous two months, no condom use at last sexual contact, and complaints of (post)coital bleeding in women and frequent urination in men. A prediction model with these risk factors showed adequate discriminative ability at internal validation (AUC 0.78). CONCLUSION: The prediction rule has the potential to guide individuals in their choice of participation when offered chlamydia screening and is a promising tool for selective CT screening at population level.

Adolescent↗

PubMed2003

Molecular variability of sunflower downy mildew, Plasmopara halstedii, from different continents.

Downy mildew of sunflower (Helianthus annuus L.), caused by the pathogen Plasmopara halstedii, is a potentially devastating disease. Seventy-seven isolates of P. halstedii collected in twelve countries from four continents were investigated for RAPD polymorphism with 21 primers. The study led to a binary matrix, which was subjected to various complementary analyses. This is the first report on the international genetic diversity of the pathogen. Similarity indices ranged from 89% to 100%. Neither a consensus unweighted pair group method with arithmetic means (UPGMA) tree constructed after bootstrap resampling of markers nor a principal component analysis based on distance matrix revealed very consistent clusterings of the isolates, and groups did not fit race or geographical origins. Phylogenies were probably obscured by limited diversity. Analysis of molecular variance (AMOVA) and Nei's genetic diversity statistics gave similar conclusions. Most of the genetic diversity was attributable to individual differences. The most differentiated races also had the lowest within-diversity indices, which suggest that they appeared recently with strong bottleneck effects. Our analyses suggest that this pathogen is probably homothallic or has an asexual mode of reproduction and that gene flow among countries can occur through commercial exchanges. Knowledge of the downy mildew populations' structure at the international level will help to devise strategies for controlling this potentially devastating disease.

DNA↗

PubMed2006

The fractal dimension of nuclear chromatin as a prognostic factor in acute precursor B lymphoblastic leukemia.

The fractal nature of the DNA arrangement has been postulated to be a common feature of all cell nuclei. We investigated the prognostic importance of the fractal dimension (FD) of chromatin in blasts of patients with acute precursor B lymphoblastic leukemia (B-ALL). In 28 patients, gray scale transformed pseudo-3D images of 100 nuclei (May-Grünwald-Giemsa stained bone marrow smears) were analyzed. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R2 values in the log-log plots. Whereas FD presented no prognostic relevance, patients with higher R2 values showed a prolonged survival. White blood cell count (WBC), age and mean fluorescence intensity of CD45 (MFICD45) were all unfavorable prognostic factors in univariate analyses. In a multivariate Cox-regression, R2, WBC, and MFICD45, entered the final model, which showed to be stable in a bootstrap resampling study. Blasts with lower R2 values, equivalent to accentuated "coarseness" of the chromatin pattern, which may reflect profound changes of the DNA methylation, indicated a poor prognosis. In conclusion the goodness-of-fit of the Minkowski-Bouligand dimension of chromatin can be regarded as a new and biologically relevant prognostic factor for patients with B-ALL.

Azure Stains↗

PubMed2005

Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.

PURPOSE: This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. EXPERIMENTAL DESIGN: Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). RESULTS: Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. CONCLUSION: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.

Adult↗

PubMed2006

Nuclear localization of nuclear factor-kappaB p65 in primary prostate tumors is highly predictive of pelvic lymph node metastases.

PURPOSE: Lymph node invasion (LNI) is associated with increased risk of prostate cancer progression. Unfortunately, pelvic lymph node dissections are fraught with a high rate of false-negative findings, emphasizing the need for highly accurate markers of LNI. Because nuclear factor-kappaB (NF-kappaB) is a candidate marker of prostate cancer progression, we tested the association between nuclear localization of NF-kappaB in radical prostatectomy specimens and the presence of LNI. EXPERIMENTAL DESIGN: NF-kappaB expression in radical prostatectomy specimens was assessed with a monoclonal NF-kappaB p65 antibody, in 20 patients with LNI and in 31 controls with no LNI and no biochemical relapse 5 years after radical prostatectomy. Univariate and multivariate logistic regression models were used. The accuracy of multivariate predictions with and without NF-kappaB was quantified with the area under the receiver operating characteristics curve and 200 bootstrap resamples were used to reduce overfit bias. RESULTS: Univariate regression models showed a 7% increase in the odds of observing LNI for each 1% increase in NF-kappaB nuclear staining (odds ratio, 1.07; P = 0.003). In multivariate models, each 1% increase in NF-kappaB was associated with an 8% increase in the odds of LNI (odds ratio, 1.08; P = 0.03) and its statistical significance was only surpassed by the presence of seminal vesicle invasion (P = 0.003). Addition of NF-kappaB to all other predictors increased the accuracy of LNI prediction by 2.3% (from 84.8% to 87.1%; P < 0.001). CONCLUSION: This is the first study that shows that the extent of nuclear localization of NF-kappaB in primary prostate tumors is highly accurately capable of predicting the probability of locoregional spread of prostate cancer.

Aged↗

PubMed2006

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.

Adult↗

PubMed2007

Robust multipoint simultaneous identical-by-descent mapping for two linked loci.

A challenging issue in genetic mapping of complex human diseases is localizing disease susceptibility genes when the genetic effects are small to moderate. There are greater complexities when multiple loci are linked to a chromosomal region. Liang et al. [Hum Hered 2001;51:64-78] proposed a robust multipoint method that can simultaneously estimate both the position of a trait locus and its effect on disease status by using affected sib pairs (ASPs). Based on the framework of generalized estimating equations (GEEs), the estimate and standard error of the position of a trait locus are robust to different genetic models. To utilize other relative pairs collected in pedigree data, Schaid et al. [Am J Hum Genet 2005;76:128-138] extended Liang's method to various types of affected relative pairs (ARPs) by two approaches: unconstrained and constrained methods. However, the above methods are limited to situations in which only one trait locus exists on the chromosome of interest. The mean functions are no longer correctly specified when there are multiple causative loci linked to a chromosomal region. To overcome this, Biernacka et al. [Genet Epidemiol 2005;28:33-47] considered the multipoint methods for ASPs to allow for two linked disease genes. We further generalize the approach to cover other types of ARPs. To reflect realistic situations for complex human diseases, we set modest sizes of genetic effects in our simulation. Our results suggest that several hundred independent pedigrees are needed, and markers with high information, to provide reliable estimates of trait locus positions and their confidence intervals. Bootstrap resampling can correct the downward bias of the robust variance for location estimates. These methods are applied to a prostate cancer linkage study on chromosome 20 and compared with the results for the one-locus model [Am J Hum Genet 2005;76:128-138]. We have implemented the multipoint IBD mapping for one and two linked loci in our software GEEARP, which allows analyses for five general types of ARPs.

Bias↗

PubMed2002

Trunk control as an early predictor of comprehensive activities of daily living function in stroke patients.

BACKGROUND AND PURPOSE: Prediction of activities of daily living (ADL) functions at an early stage after a stroke is critical because it enables clinicians to set treatment programs and goals. The objective of this study was to assess the relationship between trunk control at an early stage and comprehensive ADL function (as assessed by combining basic ADL and instrumental ADL [IADL]) in patients at 6 months after stroke. METHODS: A total of 169 stroke patients participated in this prospective study. Trunk control was measured with the use of the trunk control items of the Postural Assessment Scale for Stroke Patients (PASS-TC). In addition to the PASS-TC score, age, sex, type of stroke, side of hemiparesis, urinary incontinence, limb paresis (measured by the Fugl-Meyer motor test), balance (measured by the Fugl-Meyer balance test), and basic ADL (measured by the Barthel Index) were also selected as predictor variables. These variables were assessed at 14 days after stroke or earlier. The Barthel Index and Frenchay Activities Index (measuring IADL) were administered at 6 months after stroke. The sum of the standardized Barthel Index and standardized Frenchay Activities Index scores was used to assess comprehensive ADL function. RESULTS: Multivariable stepwise linear regression analysis showed that PASS-TC score, age, Fugl-Meyer motor test score, and Barthel Index score (listed by the order of forward selection) were the strongest predictors of comprehensive ADL function. These results were internally validated with the use of the bootstrap resampling technique. The PASS-TC score alone accounted for 45% of the variance in predicting comprehensive ADL function. Results also indicated that the PASS-TC score had slightly more power in predicting comprehensive ADL function than either the Fugl-Meyer motor test score or Barthel Index score. CONCLUSIONS: The findings of this study provide strong evidence of the predictive value of trunk control on comprehensive ADL function in stroke patients. The results imply that early assessment and management of trunk control after stroke should be emphasized.

Abdomen↗

PubMed2006

Can multivariable risk-benefit profiling be used to select treatment-favorable patients for thrombolysis in stroke in the 3- to 6-hour time window?

BACKGROUND AND PURPOSE: The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) uses multivariate equations to predict outcomes with and without thrombolysis. We sought to examine whether such a multivariate predictive instrument might be useful in selecting patients with a favorable risk-benefit treatment profile for therapy after 3 hours. METHODS: We explored outcomes in patients from 5 major randomized clinical trials testing intravenous recombinant tissue plasminogen activator (rt-PA) classified by the Stroke-TPI as "treatment-favorable" or "treatment-unfavorable." We used iterative bootstrap re-sampling to estimate how such a model would perform on independent test data. RESULTS: Among patients treated within the 3- to 6-hour window, 67% of patients were classified by Stroke-TPI predicted outcomes as "treatment-favorable" and 33% were classified as "treatment-unfavorable." Outcomes in the treatment-favorable group demonstrated benefit for thrombolysis (modified Rankin Scale score < or =1: 44.0% with rt-PA versus 34.2 with placebo, P=0.005), whereas harm was demonstrated in the treatment-unfavorable group (modified Rankin Scale score < or =1: 31.3% with rt-PA versus 38.3% with placebo; P=0.004). Bootstrap resampling with complete cross-validation showed that the absolute margin of benefit in the treatment-favorable group diminished on average by 36% between derivation and independent validation sets, but still represented a significant tripling of improvement in benefit compared with conventional inclusion criteria (5.2% [interquartile range, 1.7% to 8.6%] versus 1.8% [interquartile range, -0.5 to 4.1], P<0.0001). CONCLUSIONS: Such multivariable risk-benefit profiling may be useful in the selection of acute stroke patients for rt-PA therapy even more than 3 hours after symptom onset. Prospective testing is indicated.

Aged↗

PubMed2006

Age-dependent effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions.

BACKGROUND: No studies have specifically performed an age-based analysis of the efficacy of abciximab in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). The aim of the study was to assess whether there are age-dependent differences in the clinical benefit of abciximab in patients with acute coronary syndrome treated with PCI. METHODS AND RESULTS: We performed this retrospective analysis of 2022 patients with acute coronary syndrome enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) study and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. On the basis of the cutoff age value provided by logistic regression in connection with bootstrap resampling, patients were divided into those younger (n=1220) and older (n=802) than 70 years. Among younger patients, the incidence of MACE was 7.7% in the abciximab group versus 13.3% in the placebo group (relative risk 0.57, 95% confidence interval 0.40 to 0.80, P=0.001). In contrast, no difference was observed among older patients: The incidence of MACE was 10.9% in the abciximab group versus 9.9% in the placebo group (relative risk 1.10, 95% confidence interval 0.72 to 1.69, P=0.65). After adjustment for other variables, including cardiac troponin, there was a significant interaction between age and abciximab (P=0.04) with respect to MACE reduction, with abciximab being more effective in younger patients. CONCLUSIONS: In patients with non-ST-elevation acute coronary syndromes undergoing PCI, the efficacy of abciximab appears to be age-dependent, with greater benefit among younger patients.

Abciximab↗