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At least 793 records · Page 44Linked to original sources

PubMed2005

Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery.

Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.

Aged↗

PubMed2006

The effects of a treatment protocol for cardiac surgical patients with excessive blood loss on clinical outcomes.

BACKGROUND AND OBJECTIVES: Excessive blood loss (EBL) is a common complication of cardiac surgery that is associated with adverse events. The objective of this before/after study was to determine whether the implementation of a protocol for management of cardiac surgical patients with EBL was associated with improved clinical outcomes. MATERIALS AND METHODS: In November 2002, a protocol for prompt identification and aggressive management of cardiac surgical patients with EBL was implemented at our institution. The independent relationship between protocol implementation and adverse outcomes was measured by comparing the outcomes of patients who received > or = 4 RBC (red blood cell) units within 1 day of surgery and were operated on before protocol implementation (2000-02) with those operated on after protocol implementation (2003-05), using multivariable logistic regression analysis to control for the effects of confounders. The primary outcome was a composite of adverse events that included death, renal failure, stroke, and sepsis. Bootstrapping was used to confirm the validity of the results. RESULTS: Of the 11,314 patients who underwent surgery during the study period, 1875 (16.6%) received > or = 4 RBC units within 1 day of surgery, with 958 and 917 in the pre- and postprotocol periods, respectively. The composite adverse outcome occurred in 164 (17.1%) patients in the preprotocol period and 115 (12.5%) patients in the postprotocol period (P = 0.005). Protocol implementation was independently associated with reduced odds of the composite adverse outcome (odds ratio 0.67; 95% confidence interval 0.50, 0.91; P = 0.01). This estimate was stable in bootstrap sampling. CONCLUSION: Implementation of a protocol to manage EBL in cardiac surgery was independently associated with improved outcomes.

Aged↗

PubMed2006

Genetic analysis of Ankamali pigs of India using microsatellite markers and their comparison with other domesticated Indian pig types.

Ankamali pigs, the domesticated native pigs of Kerala province of India were genetically characterized using 23 FAO recommended microsatellite markers and were compared with other native Indian pig types and Large White pigs. Twenty-six blood samples were collected from genetically unrelated animals from their breeding tract and DNA was isolated by standard procedure of phenol/chloroform. The genomic DNA was amplified by polymerase chain reaction (PCR) at these 23 microsatellite loci, which were also used earlier to characterize Desi (North Indian) and Gahuri (North-East Indian) pigs, the other two native domesticated pig types of India. The PCR products were resolved by denaturing urea-polyacrylamide gel electrophoresis and alleles were visualized after silver nitrate staining. The data were analysed for allele size range, number of alleles, allelic frequencies, heterozygosity and polymorphism information content for each locus. The allele size range varied between 92-108 bp at locus S0026 and 280-296 bp at locus IGF-1. The total number of alleles varied between five (S0178 and S0386) and 11 (S0355). The mean observed and expected heterozygosities were found to be 0.74 +/- 0.09 and 0.83 +/- 0.03 respectively. In the neighbour-joining dendrogram based on D(A) genetic distances developed after 1000 bootstraps, the Ankamali pigs did not show genetic closeness either with other native Indian pig types or exotic Large White pigs with high bootstrap values indicating genetic distinctness of Ankamali pigs.

Alleles↗

PubMed1998

Morphological variants in keratoconus: anatomical observation or aetiologically significant?

PURPOSE: Two morphological cone variants are identified in keratoconus; nipple and oval. The present study was designed to assess the impact of aetiological factors on cone morphology. METHODS: As part of a prospective controlled study, keratoconic subjects from a suburban practice (n = 89) underwent videokeratograph examination and completed a questionnaire detailing aetiological factors. RESULTS: Comparison of 95% confidence limits (CL; bootstrap method) for apical power between the two cone morphology groups showed no statistical significance. Oval cones were located at a greater eccentricity than nipple cones, as their definitions suggest. Associations between aetiological factors examined and the morphology of the cone were not significant (bootstrapped 95% CL). CONCLUSION: Despite the suggestion of morphological variants in keratoconus, the results of the present study suggest a common cone aetiology.

Age of Onset↗

PubMed2006

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation.

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Adult↗

PubMed1997

A comparison of methods for the analysis of event-related potentials in deception detection.

We previously reported that a Bayesian-based event-related potential memory assessment procedure (Allen, Iacono, & Danielson, 1992, Psychophysiology, 29, 504-522) was highly accurate at identifying previously learned material, regardless of an individual's motivational incentive to conceal information. When a bootstrapping procedure (Farwell & Donchin, 1991, Psychophysiology, 28, 531-547) is applied to these same data, greater motivational incentives appear to increase the accuracy of the procedure. Receiver operating characteristic (ROC) curves were used to examine these two procedures and a new procedure. ROC curves indicated that all three methods produce extremely high rates of classification accuracy and that the sensitivity of the bootstrapping procedure to motivational incentive is due to the particular cut points selected. One or the other method may be preferred depending upon incentive to deceive, the cost of incorrect decisions, and the availability of extra psychophysiological data.

Adult↗

PubMedDate not supplied

Development of a parametric simulation model for forecasting goal-oriented treatment outcomes.

BACKGROUND: Treatment-to-goal (TTG) analyses are frequently used to predict guideline-directed population control rates for drug therapies based on mean efficacy data. Nevertheless, estimates are commonly inaccurate because variability in efficacy is not considered. A new methodology was developed to improve TTG forecasting. METHODS: Patient-level blood pressure (BP) lowering data sets, designed to simulate clinical trial results, were generated for testing from three underlying distributions: normal, lognormal, and beta. To emulate real-world conditions where patient-level data are unavailable, two approaches were considered: parametric--simulated BP lowering data were generated using the mean and standard deviation of the test data sets; and point-estimate--BP lowering was uniformly assigned as the mean lowering. BP control (systolic BP < 140 and diastolic BP < 90 mmHg) was forecasted by subtracting values generated by these two methods from baseline BP values in untreated hypertensive patients (n = 2483) from the Third National Health and Nutrition Examination Survey. Estimated control rates were compared to analyses where the patient-level data sets were bootstrapped. RESULTS: We assumed mean (+/- SD) BP lowering of 20 (12) mmHg systolic and 14 (7) mmHg diastolic. Parametric method predicted a BP control rate of 66.9% [95% confidence interval (CI) 65.7-67.9], similar to the bootstrapping approach (67.3%, 95% CI 65.9-68.8). The control rate projected based on the point-estimate method was 75.5%. The point-estimate method frequently led to substantially different results under a wide range of model assumptions. CONCLUSIONS: A new parametric-based forecasting method, which addresses underlying variability, improves on estimates based on mean efficacy only. In the absence of patient-level data, this method is generalizable to different therapeutic areas.

Adolescent↗

PubMedDate not supplied

Estimating the cost-effectiveness of fluticasone propionate for treating chronic obstructive pulmonary disease in the presence of missing data.

OBJECTIVES: To explore the cost-effectiveness of fluticasone propionate (FP) for the treatment of chronic obstructive pulmonary disease (COPD), we estimated costs and quality-adjusted life-years (QALYs) over 3 years, based on an economic appraisal of a previously reported clinical trial (Inhaled Steroids in Obstructive Lung Disease in Europe [ISOLDE]). METHODS: Seven hundred forty-two patients enrolled in the ISOLDE trial who received either FP or placebo had data available on health-care costs and quality of life over the period of the study. The SF-36-based utility scores for quality of life were used to calculate QALYs. A combined imputation and bootstrapping procedure was employed to handle missing data and to estimate statistical uncertainty in the estimated cumulative costs and QALYs over the study period. The imputation approach was based on propensity scoring and nesting this approach within the bootstrap ensured that multiple imputations were performed such that statistical estimates included imputation uncertainty. RESULTS: Complete data were available on mortality within the follow-up period of the study and a nonsignificant trend toward improved survival of 0.06 (95% confidence interval [CI]-0.01 to 0.15) life-years was observed. In an analysis based on a propensity scoring approach to missing data we estimated the incremental costs of FP versus placebo to be 1021 sterling pound(95% CI 619-1338 sterling pound) with an additional effect of 0.11 QALYs (CI 0.04-0.20). Cost-effectiveness estimates for the within-trial period of 17,700 sterling pound per life-year gained (6900 sterling pound to infinity) and 9500 sterling pound per QALY gained (CI 4300-26,500 sterling pound) were generated that include uncertainty due to the imputation process. An alternative imputation approach did not materially affect these estimates. CONCLUSIONS: Previous analyses of the ISOLDE study showed significant improvement on disease-specific health status measures and a trend toward a survival advantage for treatment with FP. This analysis shows that joint considerations of quality of life and survival result in a substantial increase in QALYs favoring treatment with FP. Based on these data, the inhaled corticosteroid FP appears cost-effective for the treatment of COPD. Confirmation or refutation of this result may be achieved once the Towards a Revolution in COPD Health (TORCH) study reports, a large randomized controlled trial powered to detect mortality changes associated with the use of FP alone, or in combination with salmeterol, which is also collecting resource use and utility data suitable for estimating cost-effectiveness.

Administration, Inhalation↗

PubMed2004

The independent association of massive blood loss with mortality in cardiac surgery.

BACKGROUND: Although the association between massive perioperative blood loss (MBL) and adverse outcomes is well recognized, it is unclear whether MBL is an independent risk factor or, instead, simply a marker for other adverse events or severity of illness. The objective of this cohort study was to quantify the independent association of MBL in cardiac surgery with all-cause in-hospital mortality. STUDY DESIGN AND METHODS: Data were prospectively collected on consecutive patients who underwent cardiac surgery with cardiopulmonary bypass at a quaternary-care academic center from 1999 to 2003. The number of red blood cell (RBC) units transfused within 1 day of surgery was used as a surrogate measure of perioperative blood loss. Receiver-operating characteristic curve analyses were employed to identify the most appropriate cutoff for defining MBL. The independent association of MBL with mortality was determined with multivariable logistic regression analyses. Bootstrapping and sensitivity analyses were used to confirm the validity of the results. RESULTS: MBL was defined as receiving at least 5 units of RBCs within 1 day of surgery. Of 9215 patients analyzed, 1.8 percent (n = 169) died and 9.7 percent (n = 890) had MBL. After adjusting for multiple potential confounders (including perioperative adverse events), MBL was associated with an 8.1-fold (95% confidence interval, 3.9-17.0) increase in the odds of death. This risk estimate was stable across different modeling conditions as well as in bootstrap sampling. CONCLUSION: MBL after cardiac surgery has a strong, independent association with in-hospital mortality.

Aged↗

PubMed2006

Nonparametric statistical methods for cost-effectiveness analyses.

Two measures often used in a cost-effectiveness analysis are the incremental cost-effectiveness ratio (ICER) and the net health benefit (NHB). Inferences on these two quantities are often hindered by highly skewed cost data. In this article, we derive the Edgeworth expansions for the studentized t-statistics for the two measures and show how they could be used to guide inferences. In particular, we use the expansions to study the theoretical performance of existing confidence intervals based on normal theory and to derive new confidence intervals for the ICER and the NHB. We conduct a simulation study to compare our new intervals with several existing methods. The methods evaluated include Taylor's interval, Fieller's interval, the bootstrap percentile interval, and the bootstrap bias-corrected acceleration interval. We found that our new intervals give good coverage accuracy and are narrower compared to the current recommended intervals.

Biometry↗

PubMed2001

Genetic diversity and interrelationships among common European Suillus species based on ribosomal DNA sequences.

The nucleotide sequence of the internal transcribed spacer (ITS) 1 and 2 regions was determined for 22 Suillus isolates representing seven species. Analysis of the sequence data along with 12 related sequences from databases divided the 34 isolates into seven groups, and six of these were supported by 100% bootstrap values. Isolates belonging to Suillus granulatus (0-11 divergence) were divided into three groups (SG1, SG2 and SG3); SG1 and SG2 had 100% bootstrap values. SG2 was clustered with two Suillus collinitus isolates and a Suillus variegatus isolate; SG3 was linked to a previously characterised Suillus subluteus isolate. These results clearly indicate heterogeneity among the isolates described under these species. Intra- (0.4-11) and inter- (2.4-13.6) specific divergence varied considerably. Suillus laricinus showed a high level (0.5-4.4) of intra-specific divergence. Suillus bovinus showed maximum divergence (11.4-13.3) to all other species examined. The potential of the ITS region for understanding the intra- and inter-specific relationships among Suillus species and refining their taxonomy is discussed.

Basidiomycota↗

PubMedDate not supplied

Characterizing the variability of system kernel and input estimates.

The identification of the input to, or kernels of, a system using nonparametric representations and least-squares estimation is becoming increasingly popular. Nonparametric representations avoid making a priori assumptions about the input or having detailed knowledge about the system, and only need to guarantee known general characteristics (for example, positivity), which are obtained through the imposition of constraints on the estimates. An often overlooked problem is how to characterize the variability of the estimates so obtained. This problem is caused by the presence of constraints--and/or the nonlinearities of the estimates, or the complexity of the (regression based) estimation algorithms used--which make standard methods of estimating variability incorrect. In this article we investigate the use of a resampling technique called the "bootstrap" to obtain the desired estimates of variability. We present real data analysis demonstrating the approach, and through simulations we test the performance of a novel bootstrap technique obtaining confidence bands for the estimated functions.

Algorithms↗

PubMed2005

On the comparison of FROC curves in mammography CAD systems.

We present a novel method for assessing the performance of computer-aided detection systems on unseen cases at a given sensitivity level. The sampling error introduced when training the system on a limited data set is captured as the uncertainty in determining the system threshold that would yield a certain predetermined sensitivity on unseen data sets. By estimating the distribution of system thresholds, we construct a confidence interval for the expected number of false positive markings per image at a given sensitivity. We present two alternative procedures for estimating the probability density functions needed for the construction of the confidence interval. The first is based on the common assumption of Poisson distributed number of false positive markings per image. This procedure also relies on the assumption of independence between false positives and sensitivity, an assumption that can be relaxed with the second procedure, which is nonparametric. The second procedure uses the bootstrap applied to the data generated in the leave-one-out construction of the FROC curve, and is a fast and robust way of obtaining the desired confidence interval. Standard FROC curve analysis does not account for the uncertainty in setting the system threshold, so this method should allow for a more fair comparison of different systems. The resulting confidence intervals are surprisingly wide. For our system a conventional FROC curve analysis yields 0.47 false positive markings per image at 90% sensitivity. The 90% confidence interval for the number of false positive markings per image is (0.28, 1.02) with the parametric procedure and (0.27, 1.04) with the nonparametric bootstrap. Due to its computational simplicity and its allowing more fair comparisons between systems, we propose this method as a complement to the traditionally presented FROC curves.

Algorithms↗

PubMedDate not supplied

An examination of errors in characteristic curve measurements of radiographic screen/film systems.

The precision and accuracy achieved in the measurement of characteristic curves for radiographic screen/film systems is quantitatively investigated for three techniques: inverse square, kVp bootstrap, and step-wedge bootstrap. Precision of all techniques is generally better than +/- 1.5% while the agreement among all intensity-scale techniques is better than 2% over the useful exposure latitude. However, the accuracy of the sensitometry will depend on several factors, including linearity and energy dependence of the calibration instrument, that may introduce larger errors. Comparisons of time-scale and intensity-scale methods are made and a means of measuring reciprocity law failure is demonstrated.

Radiographic Image Enhancement↗

PubMed2004

Dynamic beat-to-beat modeling of the QT-RR interval relationship: analysis of QT prolongation during alterations of autonomic state versus human ether a-go-go-related gene inhibition.

Methods to correct the QT interval for heart rate are often in disagreement and may be further confounded by changes in autonomic state. This can be problematic when trying to distinguish the changes in QT interval by either drug-induced delayed repolarization or from autonomic-mediated physiological responses. Assessment of the canine dynamic QT-RR interval relationship was visualized by novel programming of the dynamic beat-to-beat confluence of data or "clouds". To represent the nonuniformity of the clouds, a bootstrap sampling method that computes the mathematical center of the uncorrected beat-to-beat QT value (QTbtb) with upper 95% confidence bounds was adopted and compared with corrected QT (QTc) using standard correction factors. Nitroprusside-induced reflex tachycardia reduced QTbtb by 43 ms, whereas an increase of 55 and 16 ms was obtained using the Bazett (QTcB) and Fridericia (QTcF) formulae, respectively. Phenylephrine-induced reflex bradycardia increased QTbtb by 3 ms but decreased QTcB by 20 ms and QTcF by 12 ms. Delayed repolarization with E-4031 (1-[2-(6-methyl-2-pyridyl)ethyl]-4-methylsulfonylaminobenzoyl)-piperidine), an inhibitor of rectifier potassium current, increased QTbtb by 26 ms but QT prolongation calculations using QTcF and QTcB were between 12 and 52% less, respectively, when small decreases in heart rate (5-8 beats per minute) were apparent. Dynamic assessment of beat-to-beat data, using the bootstrap method, allows quantification of QT interval changes under varying conditions of heart rate, autonomic tone, and direct repolarization that may not be distinguishable with use of standard correction factors.

Adrenergic beta-Agonists↗

PubMed2006

Population pharmacokinetics of liposomal amphotericin B in pediatric patients with malignant diseases.

A population pharmacokinetic model of liposomal amphotericin B (L-AmB) in pediatric patients with malignant diseases was developed and evaluated. Blood samples were collected from 39 pediatric oncology patients who received multiple doses of L-AmB with a dose range from 0.8 to 5.9 mg/kg of body weight/day. The patient cohort had an average age of 7 years (range, 0.2 to 17 years) and weighed an average of 28.8 +/- 19.8 kg. Population pharmacokinetic analyses were performed with NONMEM software. Pharmacokinetic parameters, interindividual variability (IIV), between-occasion variability (BOV), and intraindividual variability were estimated. The influence of patient characteristics on the pharmacokinetics of L-AmB was explored. The final population pharmacokinetic model was evaluated by using a bootstrap sampling technique. The L-AmB plasma concentration-time data was described by a two-compartment pharmacokinetic model with zero-order input and first-order elimination. The population mean estimates of clearance (CL) and volume of distribution in the central compartment (V1) were 0.44 liters/h and 3.12 liters, respectively, and exhibited IIV (CL, 10%) and significant BOV (CL, 46% and V1, 56%). The covariate models were CL (liters/h) = 0.44 . e(0.0152.(WT-21)) and V1 (liters) = 3.12.e(0.0241.(WT-21)), where WT is the patient's body weight (kg) centered on the study population cohort median of 21 kg. Model evaluation by the bootstrap procedure indicated that the full pharmacokinetic model was robust and parameter estimates were accurate. In conclusion, the pharmacokinetics of L-AmB in pediatric oncology patients were adequately described by the developed population model. The model has been evaluated and can be used in the design of rational dosing strategies for L-AmB antifungal therapy in this special population.

Adolescent↗

PubMed1994

Relationship between Phylogeny and Pathotype for the Bacterial Blight Pathogen of Rice.

Several transposable elements were isolated from the genome of Xanthomonas oryzae pv. oryzae. These elements and an avirulence gene isolated from X. oryzae pv. oryzae were used as hybridization probes for a collection of X. oryzae pv. oryzae strains from the Philippines. Each of the sequences was present in multiple copies in all strains examined and showed distinct patterns of hybridizing bands. Phenograms were derived from the restriction fragment length polymorphism data obtained for each of the individual probes and for pooled data from multiple probes. The phenograms derived from the different probes differed in topology and, on the basis of bootstrap analysis, were not equally robust. For all of the probes, including the avirulence gene, some groups (even some haplotypes) consisted of multiple races. The strains were grouped into four major clusters on the basis of the two probes giving the highest bootstrap values. These groups were inferred to represent phylogenetic lineages. Three of the six races of X. oryzae pv. oryzae appeared in more than one of the lineages, and another was present in two sublineages. For three of the races, strains representing different phenetic groups were inoculated on rice cultivars carrying 10 resistance genes. Two new races were differentiated, corresponding to pathogen lineages identified by DNA typing. On the basis of DNA and pathotypic analyses, together with information on the spatial and temporal distribution of the pathogen types from this and other studies, a general picture of X. oryzae pv. oryzae evolution in the Philippines is presented.

Journal Article↗

PubMed1999

Phylogenetic classification and species identification of dermatophyte strains based on DNA sequences of nuclear ribosomal internal transcribed spacer 1 regions.

The mutual phylogenetic relationships of dermatophytes of the genera Trichophyton, Microsporum, and Epidermophyton were demonstrated by using internal transcribed spacer 1 (ITS1) region ribosomal DNA sequences. Trichophyton spp. and Microsporum spp. form a cluster in the phylogenetic tree with Epidermophyton floccosum as an outgroup, and within this cluster, all Trichophyton spp. except Trichophyton terrestre form a nested cluster (100% bootstrap support). Members of dermatophytes in the cluster of Trichophyton spp. were classified into three groups with ITS1 homologies, with each of them being a monophyletic cluster (100% bootstrap support). The Arthroderma vanbreuseghemii-Arthroderma simii group consists of A. vanbreuseghemii, A. simii, Trichophyton mentagrophytes isolates from humans, T. mentagrophytes var. quinckeanum, Trichophyton tonsurans, and Trichophyton schoenleinii. Arthroderma benhamiae, T. mentagrophytes var. erinacei, and Trichophyton verrucosum are members of the Arthroderma benhamiae group. Trichophyton rubrum and Trichophyton violaceum form the T. rubrum group. This suggests that these "species" of dermatophytes have been overclassified. The ITS1 sequences of 11 clinical isolates were also determined to identify the species, and all strains were successfully identified by comparison of their base sequences with those in the ITS1 DNA sequence database.

Arthrodermataceae↗