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C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER+) breast cancer patients with poor prognosis.

PURPOSE: To investigate the predictive value of c-erbB-2 oncoprotein expression as compared with established histopathological and cytometric indicators of disease evolution in breast carcinoma. PATIENTS AND METHODS: A short-term retrospective study was conducted on a series of 306 breast cancer patients. Classic prognostic factors included tumour size, nodal involvement, histological grading, and hormone receptor status. Flow cytometric DNA ploidy and S-phase fraction (SPF) were also assessed. A Cox proportional hazards regression model was used for multivariate statistical analysis. RESULTS: c-erbB-2 overexpression was present in 43 out of 295 (14.6%) tumours, and showed a statistically significant correlation with high histological grade, DNA aneuploidy, high SPF and lack of estrogen receptors (ER). Univariate analysis revealed its association with worse disease-free survival (DFS) and overall survival (OS). The combined evaluation of c-erbB-2 with ploidy and SPF defines a variable (P + S + c) that showed a significant correlation with disease outcome. By multivariate analysis, only nodal status (P < 0.001) and P + S + c subgrouping (group 2: P = 0.002; group 3: P = 0.001) in relation to DFS, and nodal status (P = 0.001) and DNA ploidy (P = 0.006) in relation to OS, retained independent prognostic significance. Subset analyses showed that cytometric parameters, P + S + c subgrouping and hormone receptors were significantly correlated with disease outcome in node-positive patients, whereas in node-negative subgroup no prognostic indicators were found. c-erbB-2 overexpression exhibited a trend in node-positive breast cancer (DFS: P = 0.068; OS: P = 0.086), and significant correlation with poor clinical evolution in ER positive patients (DFS: P = 0.015; OS: P = 0.004), mostly receiving tamoxifen. CONCLUSIONS: c-erbB-2 is an independent prognostic indicator of DFS when evaluated in conjunction with ploidy and SPE. It also seems to predict response to tamoxifen therapy, by identifying a subgroup of ER positive (ER+) breast cancer patients with poor prognosis.

Adult↗

A survey of biosecurity practices as risk factors affecting broiler performance on the Delmarva Peninsula.

A 10-page questionnaire on biosecurity practices was mailed to 187 growers on the Delmarva Peninsula in October 2000. The growers were selected by three broiler integrators on the basis of flock performance and were classified as cases (bottom 10% performers) and controls (top 10% performers). After two mailings, 71 growers (38%) responded to the survey, of which 47 (66.2%) represented good performers and 24 (33.8%) represented poor performers. Univariate and multivariate statistical analyses revealed that increased frequency of sanitizing water lines was statistically significantly associated with good flock performance (P = 0.0449). The presence of wild birds inside poultry houses during grow-out showed a slightly statistically significant association with poor flock performance (P = 0.0633).

Animal Husbandry↗

Effects of case removal in prognostic models.

Constructing and updating prognostic models that learn from training cases is a time-consuming task. The more compact, and yet informative, the training sets are, the faster one can build and properly evaluate such models. We have compared different regression diagnostic methods for selection and removal of training cases in prognostic models. Univariate determinations were performed using classical regression diagnostic statistics. Multivariate determinations were performed using (1) a sequential "backward" selection of cases, and (2) a non-sequential genetic algorithm. The genetic algorithm produced final models that kept few cases and retained predictive capability. A genetic algorithm approach to case selection may be better suited for guiding removal of cases in training sets than a univariate or a sequential multivariate approach, possibly because of its ability to detect sets of cases that are influential en bloc but may not be sufficiently influential when considered in isolation.

Algorithms↗

A multivariate classification study of attentional orienting in patients with right hemisphere lesions.

OBJECTIVE: To characterize patterns of orienting dysfunction that were typical to patients with lesions in the right hemisphere (RH). BACKGROUND: Brain lesions in the right hemisphere are commonly associated with dysfunction of visual orienting (e.g., visual neglect and extinction). In a clinical study of these symptoms, the multicomponent nature of attentional orienting calls upon a multivariate statistical design with careful selection of neurocognitive variables. METHODS: Thirty-eight patients with verified brain lesions and four patients with peripheral motor dysfunction after poliomyelitis were included in the study. Cognitive function was evaluated in all patients. Three reaction-time (RT) measures derived from the cue-target paradigm were selected as features in a data-driven multivariate classification scheme to generate natural subgroups of patients. RESULTS: Four subgroups were generated, with only RH patients allocated to two of them. All patients within one of the RH subgroups were characterized by a pattern of impairment earlier described as a "disengage failure" by Posner et al. ( 5, 6), signs of visual neglect on Behavioral Inattention Test, and a severely impaired cognitive function. Results for the other RH subgroup were heterogeneous on both experimental and clinical variables. Age and cognitive function were found to strongly influence two of the features, but could not predict the clusters generated from the RT measures. CONCLUSIONS: The present findings show that the cue-target paradigm together with multivariate clustering of selected feature variables can serve as a useful tool to explore and characterize patients with right hemisphere lesions. Although the concept of "disengage failure" was suited to describe the typical RT pattern in patients with neglect, other neurocognitive models and concepts can be applied to the results in the current study.

Adolescent↗

A computer program for the multivariate and graphical monitoring of acid-base data in an intensive care unit.

Monitoring the arterial acid-base status of ICU patients is done by measuring and calculating the acid-base variables pH, the partial pressure of carbon-dioxide (PCO2) and the bicarbonate-ion concentration ([HCO-3]). Univariate normal reference ranges exist for these values. However, it is well known that an exact linear relationship exists between pH, the logarithm of PCO2 and the logarithm of [HCO-3] values. We developed a computer program for the multivariate evaluation and graphical monitoring of these values in an intensive care setting that takes this intrinsic two-dimensionality into account. A composite index is introduced for the monitoring of all three laboratory values. Moreover, using this index, a multivariate statistical reference region based on an unselected population of ICU patients was derived.

Acid-Base Equilibrium↗

Intrapleural fibrinolysis for parapneumonic effusion and empyema in children.

PURPOSE: To assess the safety and efficacy of urokinase and alteplase for intrapleural fibrinolysis in children with parapneumonic pleural fluid collections. MATERIALS AND METHODS: A retrospective review was performed of 71 children with parapneumonic pleural fluid accumulations who were treated with thoracostomy tube placement and intrapleural instillation of either urokinase or alteplase. The procedures were performed with urokinase between September 2, 1995, and March 27, 1998, and with alteplase between March 30, 1998, and January 2, 2002. The medical records and daily chest radiographs were reviewed by a pediatric radiologist to ascertain demographic information, signs and symptoms, laboratory results, thoracostomy tube output, treatment details, and radiographic pleural thickness and lung opacification. Multiple variables were compared for the alteplase and urokinase groups by using univariate and multivariate statistics. We defined primary treatment success as resolution of signs and symptoms at the time of discharge, without surgical intervention. RESULTS: Primary treatment success was 98% for alteplase and 100% for urokinase, with no major complications. Greater pleural fluid drainage occurred with alteplase than urokinase during the 1st (P =.001) and 2nd (P =.002) days of fibrinolytic therapy, and for the duration of thoracostomy drainage (P <.001). Multivariate models showed greater total drainage with alteplase (P <.001), greater patient age (P <.001), larger tube size (P =.002), and greater volume of drainage during the 24 hours prior to fibrinolysis (P <.001). CONCLUSION: Intrapleural fibrinolysis with urokinase or alteplase facilitates thoracostomy tube drainage of parapneumonic pleural fluid. With the dosing regimen used in this study, alteplase produces greater thoracostomy tube output than does urokinase.

Adolescent↗

Tumour DNA ploidy as an independent prognostic factor in breast cancer.

We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P less than 0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer, primarily in cases with steroid receptor-positive tumours. In a Cox multivariate analysis DNA ploidy (P = 0.001), primary tumour size (P = 0.0007), nodal status (P = 0.04) and the content of progesterone receptors (P = 0.0008) emerged as significant independent prognostic factors, whereas oestrogen receptor status, age and menopausal status of the patients had no significant independent prognostic value. If the histological grade of ductal carcinomas was also included in the Cox model, both grade and DNA ploidy had independent prognostic effect. In conclusion, our results indicate that the analysis of DNA ploidy is a useful adjunct in the assessment of prognosis for breast cancer patients.

Aged↗

CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathological prognostic factors.

BACKGROUND: A role for CXCR3, the receptor for chemokines Mig, IP-10 and interferon-inducible T cell alpha-chemoattractant, in tumour cell migration during melanoma progression has been proposed. AIMS: To analyse CXCR3 expression in primary cutaneous malignant melanomas and its comparison with clinicopathological and prognostic factors. METHODS: A retrospective immunohistochemical study was carried out on formalin-fixed paraffin-wax-embedded sections from 82 patients with primary invasive cutaneous melanomas, with a monoclonal antibody to CXCR3 (clone 49801.111; R&D Systems). Immunoreactivity was semiquantitatively evaluated: labelling intensity (0, absent; 1, weak; 2, moderate; 3, strong) multiplied by the percentage of cells in each of the four intensity categories. A positive staining was considered when the score was >100. Melanomas were categorised by age, sex, primary site, tumour thickness, growth phase, ulceration, lymphocytic infiltration, recurrence, lymph node and distant metastasis, and survival. Univariate and multivariate statistical analyses were carried out. RESULTS: Of the 82 patients, a positive CXCR3 staining was found in 26 (31.7%) patients, whereas 56 (68.3%) were negative. In univariate analysis, a significant association of CXCR3-positive tumour cell immunostaining with tumour thickness >1 mm (p = 0.003), absence of lymphocytic infiltration (p = 0.04) and the presence of distant metastasis (p = 0.048) was found. Multivariate analysis found tumour thickness as the only independent factor with considerable association with distant metastases. CONCLUSIONS: Our findings of a positive correlation of CXCR3 tumour cell immunoreactivity in human primary cutaneous melanoma with tumour thickness >1 mm and absence of intratumoral lymphocytic infiltration support the biological implication of CXCR3 in the tumour progression of cutaneous malignant melanoma.

Adult↗

A multivariate approach to laboratory practice.

The application of multivariate statistical technics to laboratory data analysis is a recent development in clinical pathology. The proliferation in number and type of diagnostic tests requires a simple method to extract predictors of clinical states from data generated by existing laboratory procedures, as well as a method to assess the usefulness of new tests as they are proposed. A series of algorithms can select a "best predictor" subset of laboratory tests and verify this reduced group's predictive diagnostic worth. The established predictive ability of existing laboratory tests can serve as a reference scale when a newly available laboratory test is evaluated. The proposed new test is included with the best predictors already identified and confirmed. In multivariate analysis the usefulness of the proposed new procedure in the predictive diagnosis scheme is determined.

Clinical Laboratory Techniques↗

Factors associated with the development of recurrent acute otitis media--the significance of choosing the right and accurate dependent and independent variables in the multivariate analysis.

The results of univariate and multivariate statistical analysis were compared in identifying predictive factors of the development of recurrent acuta otitis media (RAOM) after an initial episode of acute otitis media (AOM) in 121 children. Univariate correlations between the development of RAOM and potential risk factors were analysed, and variables at p < 0.10 were incorporated into the stepwise multiple logistic regression analysis. The comparisons between the univariate and multivariate analysis in identifying the predictive factors were made and the importance of changing the dependent variables in the multivariate analysis was analysed. It seems that univariate analysis is over-sensitive, but multivariate analysis is over-conservative in finding possible predictors of RAOM. Choosing the right and accurate dependent and independent variables in the multivariate analysis is extremely important, when this method is used.

Acute Disease↗

Low total normal motile count values are associated with increased sperm disomy and diploidy rates in infertile patients.

This study was undertaken to evaluate the possibility of identifying men at increased risk of sperm aneuploidy and diploidy on the bases of specific cut-off values of the total normal motile count (TNMC). Twenty-seven consecutive, unselected male patients referred to our Unit were studied: 11 patients with normal sperm parameters (group A) suffering from unexplained infertility and 16 infertile patients with abnormal sperm parameters (group B). Disomy rates for chromosomes 1, 4, 8, 12, 18, X and Y were ascertained for each patient by means of triple and double fluorescence in situ hybridization (FISH) experiments. Both univariate and multivariate statistical analyses by principal component analysis (PCA) were performed for comparisons between sperm aneuploidy rates and semen quality (TNMC). TNMC scores in the two groups were significantly different (23.5 x 10(6) and 1.52 x 10(6), in groups A and B, respectively, p = 0.00002). In general, higher sperm disomy rates were noted for all chromosomes in group B compared with group A. Statistical significance was observed for disomy 1, total disomy rate (3.36% vs. 1.38%), and diploidy (0.49% vs. 0.19%) (p < 0.01). For disomy 4 and 8, differences resulted close to significance. PCA clearly showed how independent variables were inter-related. Infertile men with TNMC < 2 x 10(6) (male factor) were found to be at increased risk for sperm aneuploidy and diploidy. Multivariate analysis by PCA resulted as a useful method to visualize the information of the data sets on a bi-dimensional plot considering all the patients and all the variables at the same time.

Adult↗

Adaptive multiscale principal components analysis for online monitoring of wastewater treatment.

Fault detection and isolation (FDI) are important steps in the monitoring and supervision of industrial processes. Biological wastewater treatment (WWT) plants are difficult to model, and hence to monitor, because of the complexity of the biological reactions and because plant influent and disturbances are highly variable and/or unmeasured. Multivariate statistical models have been developed for a wide variety of situations over the past few decades, proving successful in many applications. In this paper we develop a new monitoring algorithm based on Principal Components Analysis (PCA). It can be seen equivalently as making Multiscale PCA (MSPCA) adaptive, or as a multiscale decomposition of adaptive PCA. Adaptive Multiscale PCA (AdMSPCA) exploits the changing multivariate relationships between variables at different time-scales. Adaptation of scale PCA models over time permits them to follow the evolution of the process, inputs or disturbances. Performance of AdMSPCA and adaptive PCA on a real WWT data set compared and contrasted. The most significant difference observed was the ability of AdMSPCA to adapt to a much wider range of changes. This was mainly due to the flexibility afforded by allowing each scale model to adapt whenever it did not signal an abnormal event at that scale. Relative detection speeds were examined only summarily, but seemed to depend on the characteristics of the faults/disturbances. The results of the algorithms were similar for sudden changes, but AdMSPCA appeared more sensitive to slower changes.

Algorithms↗

Multivariate analysis of risk factors for hospital mortality in valvular reoperations for prosthetic valve dysfunction.

OBJECTIVES: The purpose of the study was to analyze risk factors for hospital mortality in patients undergoing valvular reoperations for prosthetic valve dysfunction. METHODS: We performed a prospective analysis of 146 patients who underwent valvular reoperations for prosthetic valve dysfunction between July 1995 and June 1999 at the Heart Institute of the University of São Paulo Medical School. Multivariate statistical analysis with logistic regression was used to analyze preoperative and intraoperative variables to determine risk factors for hospital mortality. RESULTS: The overall hospital mortality was 10.9% (16 patients). Univariate analysis showed that the following variables were associated with higher mortality rates: advanced New York Heart Association (NYHA) functional class, increased creatinine level, prolonged extracorporeal circulation time and treatment of annular abscess. Logistic multivariate analysis identified advanced NYHA functional class and a creatinine level higher than 1.5 mg/dl as independent predictors of hospital mortality. CONCLUSIONS: Advanced NYHA functional class and higher creatinine levels were independent predictors of hospital mortality in patients submitted for valvular reoperations for prosthetic valve dysfunction.

Adolescent↗

Better decisions through science: exercise testing scores.

Statistical tools can be used to create scores for assisting in the diagnosis of coronary artery disease and assessing prognosis. General practitioners and internists frequently function as gatekeepers, deciding which patients must be referred to the cardiologist. Therefore, they need to use the basic tools they have available (ie, history, physical examination and the exercise test) in an optimal fashion. Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power compared with diagnosis only using the ST segment response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a more practical management strategy than a response of normal or abnormal. Although computers, as part of information management systems, can calculate complicated equations and derive these scores, physicians are reluctant to trust them. However, when represented as nomograms or simple additive discrete pieces of information, scores are more readily accepted. The scores have been compared with physician judgment and have been found to estimate the presence of coronary disease and prognosis as well as expert cardiologists and often better than nonspecialists. However, the discriminating power of specific variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. Should expired gases be substituted for estimated METs? Should ST/heart rate index be used instead of putting ST depression and heart rate separately into the models? Should right-sided chest leads and heart rate in recovery be considered? There is a need for further evaluation of these easily obtained variables to improve the accuracy of prediction algorithms, especially in women. The portability and reliability of scores must be ensured because access to specialized care must be safeguarded. Assessment of the clinical and exercise test data and application of the newer scores can empower the clinician to assure the cardiac patient access to appropriate and cost-effective cardiologic care.

Age Factors↗

Risk factors for early hospital readmission after cardiac operations.

OBJECTIVE: Early hospital readmissions after cardiac procedures are both costly and harmful to patients. We investigated the factors that predispose to readmission to develop strategies to minimize this problem. METHODS: As part of a prospective data collection, patients having cardiac procedures at our institution are routinely tracked for 30 days after their discharge from the hospital. We reviewed 2650 patients in our cardiac database who underwent operations over the past 5 years. We used univariate and multivariate statistical techniques to identify risks for readmission. RESULTS: Of 2574 discharged patients, 252 (9.8%) required readmission. The most common causes of readmission are cardiac (42%), pulmonary (19%), gastrointestinal (10%), extremity complications (6.7%; deep vein thrombophlebitis, peripheral arterial vascular disease, and saphenous vein harvest site problems), sternal wound problems (7.5%), and metabolic problems (4%). Of more than 70 variables studied, only 6 are significant multivariate predictors of readmission: female sex (P =.002); diabetes (P =.001); chronic lung problems (P =.011); increased distance between home and hospital (P >.001); preoperative atrial fibrillation (P =.002); and preoperative chronic renal insufficiency (P =.002). Type of operation, redo procedures, and other intraoperative and postoperative variables are not important multivariate predictors of readmission. Prolonged hospital length of stay for the initial procedure did not cause more frequent readmission. The costs of initial hospitalization (operating room costs combined with postoperative in-hospital costs) were not significantly increased in those patients who required readmission. CONCLUSIONS: The high-risk patient for readmission is a woman with diabetes, chronic lung disease, renal insufficiency, and preoperative atrial fibrillation who lives at a distance from the hospital. Readmission does not depend on periprocedural variables (eg, cardiopulmonary bypass time) or on postoperative complications. High procedural costs from the initial hospitalization do not predispose to readmission. These results suggest interventions that may reduce readmission.

Cardiac Surgical Procedures↗

Differential diagnosis of Krukenberg tumors using multivariate analysis.

AIMS AND BACKGROUND: Krukenberg tumors are ovarian metastases from a gastroenteric malignancy in 90% of cases. At present, diagnostic imaging techniques (US, CT, MRI) do not provide any reliable diagnostic criteria to differentiate these metastases from ovarian primaries. We tried to use multivariate analysis to distinguish malignant ovarian primaries from Krukenberg tumors based on their differential natural history. PATIENTS AND METHODS: We retrospectively compared the CT findings of Krukenberg tumors (47 patients, 79 masses, only from gastroenteric malignancy) with CT findings of primary epithelial ovarian cancers (46 patients, 67 masses). We compared the same independent variables in the two groups: age, morphology, margins, carcinomatosis, bilateral versus unilateral involvement, ascites, lymph node involvement, metastases on the basis of multivariate analysis. RESULTS: According to the best fitted model, clear-cut margins (OR: 3.75; 95% CI: 1.14-9.72) and the presence of carcinomatosis (OR: 4.21; 95% CI: 1.51-11.72) were the strongest predictors of a diagnosis of Krukenberg tumor. In contrast, the presence of ascites was more likely to be a protective factor (OR: 0.22; 95% CI: 0.08-0.62). CONCLUSIONS: We can try to make a differential diagnosis between a metastatic lesion from the gastroenteric tract and a primary adnexal lesion based on the multivariate statistical analysis of intraperitoneal spread of the different types of cancer rather than on morphologic findings at CT.

Adolescent↗

Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma.

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated with adjuvant hormonal or chemotherapy. The frequency of CA IX expression, its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P <.001), higher grade (P =.02), and negative estrogen receptor status (P <.001). Furthermore, CA IX expression was associated with a higher relapse rate (P =.004) and a worse overall survival (P =.001). By multivariate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P =.05). CONCLUSION: CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.

Adult↗

Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery.

PURPOSE: We performed a study to determine whether postoperative mild chemotherapy to maintain the patient's quality of life (QOL) and immunoactivity could also prolong survival. SUBJECT AND METHODS: From December 1985 to July 1988, 323 patients with completely resected primary non-small-cell lung cancer (stage I to III) were enrolled. The subjects were randomized into three treatment groups, as follows: cisplatin (CDDP) 50 mg/m2 body surface, vindesine (VDS) 2 to 3 mg/kg body weight for three courses, and 1-year oral administration of tegafur (FT) plus uracil (UFT) 400 mg/kg body weight (CVUft group, 115 patients); 1-year oral administration of UFT 400 mg/kg body weight (Uft group, 108 patients); or surgical treatment only (control group, 100 patients). RESULTS: The overall 5-year survival rates were 60.6% for the CVUft group and 64.1% for the Uft group versus 49.0% for the control group. The results of statistical testing were P = .053 (log-rank test) and P = .044 (generalized Wilcoxon test) among the three groups, P = .083 (log-rank) and P = .074 (Wilcoxon) between the CVUft and the control groups, and P = .022 (log-rank) and P = .019 (Wilcoxon) between the Uft and the control groups, which indicates higher survival rates in the CVUft and the Uft groups compared with the control group. A multivariate statistical analysis on prognostic factors using Cox's proportional hazards model was performed with the following results: P = .037, hazards ratio = 0.64 with a 95% confidence interval (CI) of 0.42 to 0.97 (control v CVUft group); and P = .009, hazards ratio = 0.55 with a 95% CI of 0.36 to 0.86 (control v Uft group). CONCLUSION: Significantly favorable results were obtained in the CVUft and Uft groups compared with surgery alone. These data showed significant prognostic advantages in the postoperative adjuvant chemotherapy groups.

Adolescent↗