Multivariate mixed linear model analysis of longitudinal data: an information-rich statistical technique for analyzing disease resistance data

USDA-ARS?s Scientific Manuscript database

The mixed linear model (MLM) is currently among the most advanced and flexible statistical modeling techniques and its use in tackling problems in plant pathology has begun surfacing in the literature. The longitudinal MLM is a multivariate extension that handles repeatedly measured data, such as r...

An efficient genome-wide association test for multivariate phenotypes based on the Fisher combination function.

PubMed

Yang, James J; Li, Jia; Williams, L Keoki; Buu, Anne

2016-01-05

In genome-wide association studies (GWAS) for complex diseases, the association between a SNP and each phenotype is usually weak. Combining multiple related phenotypic traits can increase the power of gene search and thus is a practically important area that requires methodology work. This study provides a comprehensive review of existing methods for conducting GWAS on complex diseases with multiple phenotypes including the multivariate analysis of variance (MANOVA), the principal component analysis (PCA), the generalizing estimating equations (GEE), the trait-based association test involving the extended Simes procedure (TATES), and the classical Fisher combination test. We propose a new method that relaxes the unrealistic independence assumption of the classical Fisher combination test and is computationally efficient. To demonstrate applications of the proposed method, we also present the results of statistical analysis on the Study of Addiction: Genetics and Environment (SAGE) data. Our simulation study shows that the proposed method has higher power than existing methods while controlling for the type I error rate. The GEE and the classical Fisher combination test, on the other hand, do not control the type I error rate and thus are not recommended. In general, the power of the competing methods decreases as the correlation between phenotypes increases. All the methods tend to have lower power when the multivariate phenotypes come from long tailed distributions. The real data analysis also demonstrates that the proposed method allows us to compare the marginal results with the multivariate results and specify which SNPs are specific to a particular phenotype or contribute to the common construct. The proposed method outperforms existing methods in most settings and also has great applications in GWAS on complex diseases with multiple phenotypes such as the substance abuse disorders.

CD147 as a novel biomarker for predicting the prognosis and clinicopathological features of bladder cancer: a meta-analysis

PubMed Central

Li, Hongru; Xu, Yadong; Li, Hui

2017-01-01

Objective To assess the prognostic and clinicopathological characteristics of CD147 in human bladder cancer. Methods Studies on CD147 expression in bladder cancer were retrieved from PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, and the WanFang databases. Outcomes were pooled with meta-analyzing softwares RevMan 5.3 and STATA 14.0. Results Twenty-four studies with 25 datasets demonstrated that CD147 expression was higher in bladder cancer than in non-cancer tissues (OR=43.64, P<0.00001). Moreover, this increase was associated with more advanced clinical stages (OR=73.89, P<0.0001), deeper invasion (OR=3.22, P<0.00001), lower histological differentiation (OR=4.54, P=0.0005), poorer overall survival (univariate analysis, HR=2.63, P<0.00001; multivariate analysis, HR=1.86, P=0.00036), disease specific survival (univariate analysis, HR=1.65, P=0.002), disease recurrence-free survival (univariate analysis, HR=2.78, P=0.001; multivariate analysis, HR=5.51, P=0.017), rate of recurrence (OR=1.91, P=0.0006), invasive depth (pT2∼T4 vs. pTa∼T1; OR=3.22, P<0.00001), and histological differentiation (low versus moderate-to-high; OR=4.54, P=0.0005). No difference was found among disease specific survival in multivariate analysis (P=0.067), lymph node metastasis (P=0.12), and sex (P=0.15). Conclusion CD147 could be a biomarker for early diagnosis, treatment, and prognosis of bladder cancer. PMID:28977970

MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma.

PubMed

Re, Massimo; Çeka, Artan; Rubini, Corrado; Ferrante, Luigi; Zizzi, Antonio; Gioacchini, Federico M; Tulli, Michele; Spazzafumo, Liana; Sellari-Franceschini, Stefano; Procopio, Antonio D; Olivieri, Fabiola

2015-09-01

Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. Retrospective cohort study. Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

PubMed Central

Augustin, Regina; Lichtenthaler, Stefan F.; Greeff, Michael; Hansen, Jens; Wurst, Wolfgang; Trümbach, Dietrich

2011-01-01

The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD) pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases. PMID:21559189

[Methods of the multivariate statistical analysis of so-called polyetiological diseases using the example of coronary heart disease].

PubMed

Lifshits, A M

1979-01-01

General characteristics of the multivariate statistical analysis (MSA) is given. Methodical premises and criteria for the selection of an adequate MSA method applicable to pathoanatomic investigations of the epidemiology of multicausal diseases are presented. The experience of using MSA with computors and standard computing programs in studies of coronary arteries aterosclerosis on the materials of 2060 autopsies is described. The combined use of 4 MSA methods: sequential, correlational, regressional, and discriminant permitted to quantitate the contribution of each of the 8 examined risk factors in the development of aterosclerosis. The most important factors were found to be the age, arterial hypertension, and heredity. Occupational hypodynamia and increased fatness were more important in men, whereas diabetes melitus--in women. The registration of this combination of risk factors by MSA methods provides for more reliable prognosis of the likelihood of coronary heart disease with a fatal outcome than prognosis of the degree of coronary aterosclerosis.

A retrospective analysis of oral cholera vaccine use, disease severity and deaths during an outbreak in South Sudan.

PubMed

Bekolo, Cavin Epie; van Loenhout, Joris Adriaan Frank; Rodriguez-Llanes, Jose Manuel; Rumunu, John; Ramadan, Otim Patrick; Guha-Sapir, Debarati

2016-09-01

To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. The study involved a retrospective analysis of demographic and clinical data from 41 cholera treatment facilities in South Sudan on patients who developed cholera disease between 23 April and 20 July 2014 during a large outbreak, a few months after a pre-emptive oral vaccination campaign. Patients who developed severe dehydration were regarded as having a severe cholera infection. Vaccinated and unvaccinated patients were compared and multivariate logistic regression analysis was used to identify factors associated with developing severe disease or death. In total, 4115 cholera patients were treated at the 41 facilities: 1946 (47.3%) had severe disease and 62 (1.5%) deaths occurred. Multivariate analysis showed that patients who received two doses of oral cholera vaccine were 4.5-fold less likely to develop severe disease than unvaccinated patients (adjusted odds ratio, aOR: 0.22; 95% confidence interval, CI: 0.11-0.44). Moreover, those with severe cholera were significantly more likely to die than those without (aOR: 4.76; 95% CI: 2.33-9.77). Pre-emptive vaccination with two doses of oral cholera vaccine was associated with a significant reduction in the likelihood of developing severe cholera disease during an outbreak in South Sudan. Moreover, severe disease was the strongest predictor of death. Two doses of oral cholera vaccine should be used in emergencies to reduce the disease burden.

Smoking-associated factors in myocardial infarction and unstable angina: do gender differences exist?

PubMed

Perez, Glória Heloise; Nicolau, José Carlos; Romano, Bellkiss Wilma; Laranjeira, Ronaldo

2007-06-01

The aim of this study was to investigate demographic and psychological characteristics associated with smoking in patients with acute coronary syndrome (myocardial infarction or unstable angina). Interviews were conducted with 348 consecutive hospitalized patients with acute coronary syndrome and included questions about demographic characteristics, coffee consumption, heart disease risk perception, economic status, alcohol consumption, depression, anxiety, and stress. Female group multivariate analysis showed that smoking in females was significantly and negatively associated with age, heart disease risk perception, and positively associated with coffee consumption. Male group multivariate analysis showed that for males, smoking was significantly and negatively associated with age, heart disease risk perception, and positively associated with coffee and alcohol consumption. Unlike studies conducted with non-heart disease patients, our results do not show an association between smoking and depression. Compared with nonsmokers, smokers with acute coronary syndrome are younger, more likely to drink coffee, and less likely to perceive smoking as a heart disease risk. Male smokers are also more likely to drink alcohol, indicating that they use more psycho-stimulants than do nonsmoking men and women who smoke.

The association between body mass index and severe biliary infections: a multivariate analysis.

PubMed

Stewart, Lygia; Griffiss, J McLeod; Jarvis, Gary A; Way, Lawrence W

2012-11-01

Obesity has been associated with worse infectious disease outcomes. It is a risk factor for cholesterol gallstones, but little is known about associations between body mass index (BMI) and biliary infections. We studied this using factors associated with biliary infections. A total of 427 patients with gallstones were studied. Gallstones, bile, and blood (as applicable) were cultured. Illness severity was classified as follows: none (no infection or inflammation), systemic inflammatory response syndrome (fever, leukocytosis), severe (abscess, cholangitis, empyema), or multi-organ dysfunction syndrome (bacteremia, hypotension, organ failure). Associations between BMI and biliary bacteria, bacteremia, gallstone type, and illness severity were examined using bivariate and multivariate analysis. BMI inversely correlated with pigment stones, biliary bacteria, bacteremia, and increased illness severity on bivariate and multivariate analysis. Obesity correlated with less severe biliary infections. BMI inversely correlated with pigment stones and biliary bacteria; multivariate analysis showed an independent correlation between lower BMI and illness severity. Most patients with severe biliary infections had a normal BMI, suggesting that obesity may be protective in biliary infections. This study examined the correlation between BMI and biliary infection severity. Published by Elsevier Inc.

Neurodevelopmental Status and Adaptive Behaviors in Preschool Children with Chronic Kidney Disease

ERIC Educational Resources Information Center

Duquette, Peter J.; Hooper, Stephen R.; Icard, Phil F.; Hower, Sarah J.; Mamak, Eva G.; Wetherington, Crista E.; Gipson, Debbie S.

2009-01-01

This study examines the early neurodevelopmental function of infants and preschool children who have chronic kidney disease (CKD). Fifteen patients with CKD are compared to a healthy control group using the "Mullen Scales of Early Learning" (MSEL) and the "Vineland Adaptive Behavior Scale" (VABS). Multivariate analysis reveals…

[Prevalence and factors associated with renal disease among patients with newly diagnoses of HIV in Brazzaville, Republic of Congo].

PubMed

Ekat, M H; Courpotin, C; Diafouka, M; Akolbout, M; Mahambou-Nsonde, D; Bitsindou, P R; Nzounza, P; Simon, B

2013-05-01

The aim of this study was to determine the prevalence of kidney disease in patients newly diagnosed as HIV-positive in Brazzaville and to identify the associated risk factors. Descriptive and analytical study of patients diagnosed with HIV infection at the Ambulatory Treatment Center in Brazzaville, Republic of Congo, from January 1, 2009, through December 31, 2010. Estimated glomerular filtration rate (eGFR) was assessed with the Modification of Diet in Renal Disease equation (MDRD-GFR), and kidney disease was defined by an eGFR less than 60 mL/min/1.73 m(2). We conducted a univariate and then a multivariate logistic regression analysis to determine the factors associated with kidney disease in this population. The study included 562 patients newly identified as HIV-infected, 66.13% of whom were women. Their median age was 38.84 years interquartile range (IQR): 33.18-46.23) and their median body mass index (BMI) 20.31 kg/m(2) (IQR: 17.97-22.89). Their median CD4 count was 192 cells/mm(3) (IQR: 81-350), and 70.8% were at WHO stage III/IV. Finally, the median MDRD-GFR was 95.59 (IQR: 78.76-114.92) mL/min/1.73 m(2) and 8.5% had a GFR less than 60 mL/min/1.73 m(2), that is, moderate impairment of kidney function. The only factor associated with kidney disease in the multivariate analysis was a BMI less than 18.5 kg/m(2) (adjusted odds ratio: 2.54, 95% confidence interval: 1.25-5.15, p = 0.01). The prevalence of kidney disease in patients newly diagnosed with HIV in Brazzaville is relatively high. The only factor associated with it in the multivariate analysis was a BMI less than 18.5 kg/m(2).

Multivariate Analysis As a Support for Diagnostic Flowcharts in Allergic Bronchopulmonary Aspergillosis: A Proof-of-Concept Study.

PubMed

Vitte, Joana; Ranque, Stéphane; Carsin, Ania; Gomez, Carine; Romain, Thomas; Cassagne, Carole; Gouitaa, Marion; Baravalle-Einaudi, Mélisande; Bel, Nathalie Stremler-Le; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Gaudart, Jean

2017-01-01

Molecular-based allergy diagnosis yields multiple biomarker datasets. The classical diagnostic score for allergic bronchopulmonary aspergillosis (ABPA), a severe disease usually occurring in asthmatic patients and people with cystic fibrosis, comprises succinct immunological criteria formulated in 1977: total IgE, anti- Aspergillus fumigatus ( Af ) IgE, anti- Af "precipitins," and anti- Af IgG. Progress achieved over the last four decades led to multiple IgE and IgG(4) Af biomarkers available with quantitative, standardized, molecular-level reports. These newly available biomarkers have not been included in the current diagnostic criteria, either individually or in algorithms, despite persistent underdiagnosis of ABPA. Large numbers of individual biomarkers may hinder their use in clinical practice. Conversely, multivariate analysis using new tools may bring about a better chance of less diagnostic mistakes. We report here a proof-of-concept work consisting of a three-step multivariate analysis of Af IgE, IgG, and IgG4 biomarkers through a combination of principal component analysis, hierarchical ascendant classification, and classification and regression tree multivariate analysis. The resulting diagnostic algorithms might show the way for novel criteria and improved diagnostic efficiency in Af -sensitized patients at risk for ABPA.

Identification of Reliable Components in Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS): a Data-Driven Approach across Metabolic Processes.

PubMed

Motegi, Hiromi; Tsuboi, Yuuri; Saga, Ayako; Kagami, Tomoko; Inoue, Maki; Toki, Hideaki; Minowa, Osamu; Noda, Tetsuo; Kikuchi, Jun

2015-11-04

There is an increasing need to use multivariate statistical methods for understanding biological functions, identifying the mechanisms of diseases, and exploring biomarkers. In addition to classical analyses such as hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis, various multivariate strategies, including independent component analysis, non-negative matrix factorization, and multivariate curve resolution, have recently been proposed. However, determining the number of components is problematic. Despite the proposal of several different methods, no satisfactory approach has yet been reported. To resolve this problem, we implemented a new idea: classifying a component as "reliable" or "unreliable" based on the reproducibility of its appearance, regardless of the number of components in the calculation. Using the clustering method for classification, we applied this idea to multivariate curve resolution-alternating least squares (MCR-ALS). Comparisons between conventional and modified methods applied to proton nuclear magnetic resonance ((1)H-NMR) spectral datasets derived from known standard mixtures and biological mixtures (urine and feces of mice) revealed that more plausible results are obtained by the modified method. In particular, clusters containing little information were detected with reliability. This strategy, named "cluster-aided MCR-ALS," will facilitate the attainment of more reliable results in the metabolomics datasets.

Multivariate analysis of longitudinal rates of change.

PubMed

Bryan, Matthew; Heagerty, Patrick J

2016-12-10

Longitudinal data allow direct comparison of the change in patient outcomes associated with treatment or exposure. Frequently, several longitudinal measures are collected that either reflect a common underlying health status, or characterize processes that are influenced in a similar way by covariates such as exposure or demographic characteristics. Statistical methods that can combine multivariate response variables into common measures of covariate effects have been proposed in the literature. Current methods for characterizing the relationship between covariates and the rate of change in multivariate outcomes are limited to select models. For example, 'accelerated time' methods have been developed which assume that covariates rescale time in longitudinal models for disease progression. In this manuscript, we detail an alternative multivariate model formulation that directly structures longitudinal rates of change and that permits a common covariate effect across multiple outcomes. We detail maximum likelihood estimation for a multivariate longitudinal mixed model. We show via asymptotic calculations the potential gain in power that may be achieved with a common analysis of multiple outcomes. We apply the proposed methods to the analysis of a trivariate outcome for infant growth and compare rates of change for HIV infected and uninfected infants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study.

PubMed

Hicks, Lucy C; Huang, Juzheng; Kumar, Sacheen; Powles, Sam T; Orchard, Timothy R; Hanna, George B; Williams, Horace R T

2015-09-01

Distinguishing between the inflammatory bowel diseases [IBD], Crohn's disease [CD] and ulcerative colitis [UC], is important for determining management and prognosis. Selected ion flow tube mass spectrometry [SIFT-MS] may be used to analyse volatile organic compounds [VOCs] in exhaled breath: these may be altered in disease states, and distinguishing breath VOC profiles can be identified. The aim of this pilot study was to identify, quantify, and analyse VOCs present in the breath of IBD patients and controls, potentially providing insights into disease pathogenesis and complementing current diagnostic algorithms. SIFT-MS breath profiling of 56 individuals [20 UC, 18 CD, and 18 healthy controls] was undertaken. Multivariate analysis included principal components analysis and partial least squares discriminant analysis with orthogonal signal correction [OSC-PLS-DA]. Receiver operating characteristic [ROC] analysis was performed for each comparative analysis using statistically significant VOCs. OSC-PLS-DA modelling was able to distinguish both CD and UC from healthy controls and from one other with good sensitivity and specificity. ROC analysis using combinations of statistically significant VOCs [dimethyl sulphide, hydrogen sulphide, hydrogen cyanide, ammonia, butanal, and nonanal] gave integrated areas under the curve of 0.86 [CD vs healthy controls], 0.74 [UC vs healthy controls], and 0.83 [CD vs UC]. Exhaled breath VOC profiling was able to distinguish IBD patients from controls, as well as to separate UC from CD, using both multivariate and univariate statistical techniques. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Multivariate analysis of maize disease resistances suggests a pleiotropic genetic basis and implicates a glutathione S-transferase gene

USDA-ARS?s Scientific Manuscript database

Plants are attacked by pathogens representing diverse taxonomic groups, such that genes providing multiple disease resistance (MDR) would likely be under positive selection pressure. We examined the novel proposition that naturally occurring allelic variants may confer MDR. To do so, we applied a ...

Multivariate Meta-Analysis of Preference-Based Quality of Life Values in Coronary Heart Disease.

PubMed

Stevanović, Jelena; Pechlivanoglou, Petros; Kampinga, Marthe A; Krabbe, Paul F M; Postma, Maarten J

2016-01-01

There are numerous health-related quality of life (HRQol) measurements used in coronary heart disease (CHD) in the literature. However, only values assessed with preference-based instruments can be directly applied in a cost-utility analysis (CUA). To summarize and synthesize instrument-specific preference-based values in CHD and the underlying disease-subgroups, stable angina and post-acute coronary syndrome (post-ACS), for developed countries, while accounting for study-level characteristics, and within- and between-study correlation. A systematic review was conducted to identify studies reporting preference-based values in CHD. A multivariate meta-analysis was applied to synthesize the HRQoL values. Meta-regression analyses examined the effect of study level covariates age, publication year, prevalence of diabetes and gender. A total of 40 studies providing preference-based values were detected. Synthesized estimates of HRQoL in post-ACS ranged from 0.64 (Quality of Well-Being) to 0.92 (EuroQol European"tariff"), while in stable angina they ranged from 0.64 (Short form 6D) to 0.89 (Standard Gamble). Similar findings were observed in estimates applying to general CHD. No significant improvement in model fit was found after adjusting for study-level covariates. Large between-study heterogeneity was observed in all the models investigated. The main finding of our study is the presence of large heterogeneity both within and between instrument-specific HRQoL values. Current economic models in CHD ignore this between-study heterogeneity. Multivariate meta-analysis can quantify this heterogeneity and offers the means for uncertainty around HRQoL values to be translated to uncertainty in CUAs.

NMR Spectroscopy Identifies Metabolites Translocated from Powdery Mildew Resistant Rootstocks to Susceptible Watermelon Scions.

PubMed

Mahmud, Iqbal; Kousik, Chandrasekar; Hassell, Richard; Chowdhury, Kamal; Boroujerdi, Arezue F

2015-09-16

Powdery mildew (PM) disease causes significant loss in watermelon. Due to the unavailability of a commercial watermelon variety that is resistant to PM, grafting susceptible cultivars on wild resistant rootstocks is being explored as a short-term management strategy to combat this disease. Nuclear magnetic resonance-based metabolic profiles of susceptible and resistant rootstocks of watermelon and their corresponding susceptible scions (Mickey Lee) were compared to screen for potential metabolites related to PM resistance using multivariate principal component analysis. Significant score plot differences between the susceptible and resistant groups were revealed through Mahalanobis distance analysis. Significantly different spectral buckets and their corresponding metabolites (including choline, fumarate, 5-hydroxyindole-3-acetate, and melatonin) have been identified quantitatively using multivariate loading plots and verified by volcano plot analyses. The data suggest that these metabolites were translocated from the powdery mildew resistant rootstocks to their corresponding powdery mildew susceptible scions and can be related to PM disease resistance.

Testing Mean Differences among Groups: Multivariate and Repeated Measures Analysis with Minimal Assumptions

PubMed Central

Bathke, Arne C.; Friedrich, Sarah; Pauly, Markus; Konietschke, Frank; Staffen, Wolfgang; Strobl, Nicolas; Höller, Yvonne

2018-01-01

ABSTRACT To date, there is a lack of satisfactory inferential techniques for the analysis of multivariate data in factorial designs, when only minimal assumptions on the data can be made. Presently available methods are limited to very particular study designs or assume either multivariate normality or equal covariance matrices across groups, or they do not allow for an assessment of the interaction effects across within-subjects and between-subjects variables. We propose and methodologically validate a parametric bootstrap approach that does not suffer from any of the above limitations, and thus provides a rather general and comprehensive methodological route to inference for multivariate and repeated measures data. As an example application, we consider data from two different Alzheimer’s disease (AD) examination modalities that may be used for precise and early diagnosis, namely, single-photon emission computed tomography (SPECT) and electroencephalogram (EEG). These data violate the assumptions of classical multivariate methods, and indeed classical methods would not have yielded the same conclusions with regards to some of the factors involved. PMID:29565679

NIH disease funding levels and burden of disease.

PubMed

Gillum, Leslie A; Gouveia, Christopher; Dorsey, E Ray; Pletcher, Mark; Mathers, Colin D; McCulloch, Charles E; Johnston, S Claiborne

2011-02-24

An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.

Discerning mild cognitive impairment and Alzheimer Disease from normal aging: morphologic characterization based on univariate and multivariate models.

PubMed

Liao, Weiqi; Long, Xiaojing; Jiang, Chunxiang; Diao, Yanjun; Liu, Xin; Zheng, Hairong; Zhang, Lijuan

2014-05-01

Differentiating mild cognitive impairment (MCI) and Alzheimer Disease (AD) from healthy aging remains challenging. This study aimed to explore the cerebral structural alterations of subjects with MCI or AD as compared to healthy elderly based on the individual and collective effects of cerebral morphologic indices using univariate and multivariate analyses. T1-weighted images (T1WIs) were retrieved from Alzheimer Disease Neuroimaging Initiative database for 116 subjects who were categorized into groups of healthy aging, MCI, and AD. Analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) were performed to explore the intergroup morphologic alterations indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume with age and sex controlled as covariates, in 34 parcellated gyri regions of interest (ROIs) for both cerebral hemispheres based on the T1WI. Statistical parameters were mapped on the anatomic images to facilitate visual inspection. Global rather than region-specific structural alterations were revealed in groups of MCI and AD relative to healthy elderly using MANCOVA. ANCOVA revealed that the cortical thickness decreased more prominently in entorhinal, temporal, and cingulate cortices and was positively correlated with patients' cognitive performance in AD group but not in MCI. The temporal lobe features marked atrophy of white matter during the disease dynamics. Significant intercorrelations were observed among the morphologic indices with univariate analysis for given ROIs. Significant global structural alterations were identified in MCI and AD based on MANCOVA model with improved sensitivity. The intercorrelation among the morphologic indices may dampen the use of individual morphological parameter in featuring cerebral structural alterations. Decrease in cortical thickness is not reflective of the cognitive performance at the early stage of AD. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

PubMed Central

Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

2012-01-01

Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: NCT00020943. PMID:22102709

[Analysis of the prevalence and risk factors of preoperative angiography confirmed coronary artery stenosis in patients with degenerative valvular heart disease].

PubMed

Xu, Z J; Pan, J; Zhou, Q; Wang, D J

2017-10-24

Objective: To estimate the prevalence and the risk factors of preoperative coronary angiography (CAG) confirmed coronary stenosis in patients with degenerative valvular heart disease. Methods: A total of 491 patients who underwent screening CAG before valvular surgery due to degenerative valvular heart disease were enrolled from January 2011 to September 2014 in our hospital, and clinical data were analyzed. According to CAG results, patients were divided into positive CAG result (PCAG) group or negative CAG (NCAG) group. Positive CAG result was defined as stenosis ≥50% of the diameter of the left main coronary artery or stenosis ≥70% of the diameter of left anterior descending, left circumflex artery, and right coronary artery.Risk factors of positive CAG result were analyzed by multivariable logistic regression analysis, and Bootstrap method was used to verify the results. Results: There were 47(9.57%)degenerative valvular heart disease patients with PCAG. Patients were older ((68.0±7.6)years vs.(62.6±7.1)years, P <0.001) and the prevalence of typical angina was significantly higher (14.89%(7/47)vs. 2.03%(9/444), P <0.001)in PCAG group than in NCAG group. Multivariable logistic regression analysis showed that age ( OR =1.118, 95% CI 1.067-1.172, P <0.001), typical angina ( OR =8.970, 95% CI 2.963-27.154, P <0.001), and serum concentration of apolipoprotein B ( OR =20.311, 95% CI 4.774-86.416, P <0.001) were the independent risk factors of PCAG in degenerative valvular heart disease patients. Bootstrap method revealed satisfactory repeatability of multivariable logistic regression analysis results (age: OR =1.118, 95% CI 1.068-1.178, P =0.001; typical angina: OR =8.970, 95% CI 2.338-35.891, P =0.001; serum concentration of apolipoprotein B: OR =20.311, 95% CI 4.639-91.977, P =0.001). Conclusions: A low prevalence of PCAG before valvular surgery is observed in degenerative valvular heart disease patients in this patient cohort. Age, typical angina, and serum concentration of apolipoprotein B are independent risk factors of PCAG in this patient cohort.

Multivariate Analysis of Longitudinal Rates of Change

PubMed Central

Bryan, Matthew; Heagerty, Patrick J.

2016-01-01

Longitudinal data allow direct comparison of the change in patient outcomes associated with treatment or exposure. Frequently, several longitudinal measures are collected that either reflect a common underlying health status, or characterize processes that are influenced in a similar way by covariates such as exposure or demographic characteristics. Statistical methods that can combine multivariate response variables into common measures of covariate effects have been proposed by Roy and Lin [1]; Proust-Lima, Letenneur and Jacqmin-Gadda [2]; and Gray and Brookmeyer [3] among others. Current methods for characterizing the relationship between covariates and the rate of change in multivariate outcomes are limited to select models. For example, Gray and Brookmeyer [3] introduce an “accelerated time” method which assumes that covariates rescale time in longitudinal models for disease progression. In this manuscript we detail an alternative multivariate model formulation that directly structures longitudinal rates of change, and that permits a common covariate effect across multiple outcomes. We detail maximum likelihood estimation for a multivariate longitudinal mixed model. We show via asymptotic calculations the potential gain in power that may be achieved with a common analysis of multiple outcomes. We apply the proposed methods to the analysis of a trivariate outcome for infant growth and compare rates of change for HIV infected and uninfected infants. PMID:27417129

A functional U-statistic method for association analysis of sequencing data.

PubMed

Jadhav, Sneha; Tong, Xiaoran; Lu, Qing

2017-11-01

Although sequencing studies hold great promise for uncovering novel variants predisposing to human diseases, the high dimensionality of the sequencing data brings tremendous challenges to data analysis. Moreover, for many complex diseases (e.g., psychiatric disorders) multiple related phenotypes are collected. These phenotypes can be different measurements of an underlying disease, or measurements characterizing multiple related diseases for studying common genetic mechanism. Although jointly analyzing these phenotypes could potentially increase the power of identifying disease-associated genes, the different types of phenotypes pose challenges for association analysis. To address these challenges, we propose a nonparametric method, functional U-statistic method (FU), for multivariate analysis of sequencing data. It first constructs smooth functions from individuals' sequencing data, and then tests the association of these functions with multiple phenotypes by using a U-statistic. The method provides a general framework for analyzing various types of phenotypes (e.g., binary and continuous phenotypes) with unknown distributions. Fitting the genetic variants within a gene using a smoothing function also allows us to capture complexities of gene structure (e.g., linkage disequilibrium, LD), which could potentially increase the power of association analysis. Through simulations, we compared our method to the multivariate outcome score test (MOST), and found that our test attained better performance than MOST. In a real data application, we apply our method to the sequencing data from Minnesota Twin Study (MTS) and found potential associations of several nicotine receptor subunit (CHRN) genes, including CHRNB3, associated with nicotine dependence and/or alcohol dependence. © 2017 WILEY PERIODICALS, INC.

When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

PubMed

Papadia, Andrea; Bellati, Filippo; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Donfrancesco, Cristina; Gasparri, Maria Luisa; Raspagliesi, Francesco

2015-12-01

The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

A detailed comparison of analysis processes for MCC-IMS data in disease classification—Automated methods can replace manual peak annotations

PubMed Central

Horsch, Salome; Kopczynski, Dominik; Kuthe, Elias; Baumbach, Jörg Ingo; Rahmann, Sven

2017-01-01

Motivation Disease classification from molecular measurements typically requires an analysis pipeline from raw noisy measurements to final classification results. Multi capillary column—ion mobility spectrometry (MCC-IMS) is a promising technology for the detection of volatile organic compounds in the air of exhaled breath. From raw measurements, the peak regions representing the compounds have to be identified, quantified, and clustered across different experiments. Currently, several steps of this analysis process require manual intervention of human experts. Our goal is to identify a fully automatic pipeline that yields competitive disease classification results compared to an established but subjective and tedious semi-manual process. Method We combine a large number of modern methods for peak detection, peak clustering, and multivariate classification into analysis pipelines for raw MCC-IMS data. We evaluate all combinations on three different real datasets in an unbiased cross-validation setting. We determine which specific algorithmic combinations lead to high AUC values in disease classifications across the different medical application scenarios. Results The best fully automated analysis process achieves even better classification results than the established manual process. The best algorithms for the three analysis steps are (i) SGLTR (Savitzky-Golay Laplace-operator filter thresholding regions) and LM (Local Maxima) for automated peak identification, (ii) EM clustering (Expectation Maximization) and DBSCAN (Density-Based Spatial Clustering of Applications with Noise) for the clustering step and (iii) RF (Random Forest) for multivariate classification. Thus, automated methods can replace the manual steps in the analysis process to enable an unbiased high throughput use of the technology. PMID:28910313

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

PubMed

Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X

2016-03-08

To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

Detection of cervical lesions by multivariate analysis of diffuse reflectance spectra: a clinical study.

PubMed

Prabitha, Vasumathi Gopala; Suchetha, Sambasivan; Jayanthi, Jayaraj Lalitha; Baiju, Kamalasanan Vijayakumary; Rema, Prabhakaran; Anuraj, Koyippurath; Mathews, Anita; Sebastian, Paul; Subhash, Narayanan

2016-01-01

Diffuse reflectance (DR) spectroscopy is a non-invasive, real-time, and cost-effective tool for early detection of malignant changes in squamous epithelial tissues. The present study aims to evaluate the diagnostic power of diffuse reflectance spectroscopy for non-invasive discrimination of cervical lesions in vivo. A clinical trial was carried out on 48 sites in 34 patients by recording DR spectra using a point-monitoring device with white light illumination. The acquired data were analyzed and classified using multivariate statistical analysis based on principal component analysis (PCA) and linear discriminant analysis (LDA). Diagnostic accuracies were validated using random number generators. The receiver operating characteristic (ROC) curves were plotted for evaluating the discriminating power of the proposed statistical technique. An algorithm was developed and used to classify non-diseased (normal) from diseased sites (abnormal) with a sensitivity of 72 % and specificity of 87 %. While low-grade squamous intraepithelial lesion (LSIL) could be discriminated from normal with a sensitivity of 56 % and specificity of 80 %, and high-grade squamous intraepithelial lesion (HSIL) from normal with a sensitivity of 89 % and specificity of 97 %, LSIL could be discriminated from HSIL with 100 % sensitivity and specificity. The areas under the ROC curves were 0.993 (95 % confidence interval (CI) 0.0 to 1) and 1 (95 % CI 1) for the discrimination of HSIL from normal and HSIL from LSIL, respectively. The results of the study show that DR spectroscopy could be used along with multivariate analytical techniques as a non-invasive technique to monitor cervical disease status in real time.

Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis

PubMed Central

D'Ovidio, Valeria; Meo, Donatella; Viscido, Angelo; Bresci, Giampaolo; Vernia, Piero; Caprilli, Renzo

2011-01-01

AIM: To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS: Sixty-nine ulcerative colitis patients (39 F, 30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency, clinical activity index (CAI), C reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), values at baseline, use of immunosuppressant, duration of disease, and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS: In the univariate analysis, CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390, 95% Confidence interval (CI): 0.176-0.865, Wald 5.361, P = 0.0160] and low CAI levels at baseline (4 < CAI < 7) (OR = 0.770, 95% CI: 0.425-1.394, Wald 3.747, P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION: GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo. PMID:21528055

Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.

PubMed

Papadia, Andrea; Bellati, Filippo; Ditto, Antonino; Bogani, Giorgio; Gasparri, Maria Luisa; Di Donato, Violante; Martinelli, Fabio; Lorusso, Domenica; Benedetti-Panici, Pierluigi; Raspagliesi, Francesco

2015-12-01

Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

Multiscale Characterization of PM2.5 in Southern Taiwan based on Noise-assisted Multivariate Empirical Mode Decomposition and Time-dependent Intrinsic Correlation

NASA Astrophysics Data System (ADS)

Hsiao, Y. R.; Tsai, C.

2017-12-01

As the WHO Air Quality Guideline indicates, ambient air pollution exposes world populations under threat of fatal symptoms (e.g. heart disease, lung cancer, asthma etc.), raising concerns of air pollution sources and relative factors. This study presents a novel approach to investigating the multiscale variations of PM2.5 in southern Taiwan over the past decade, with four meteorological influencing factors (Temperature, relative humidity, precipitation and wind speed),based on Noise-assisted Multivariate Empirical Mode Decomposition(NAMEMD) algorithm, Hilbert Spectral Analysis(HSA) and Time-dependent Intrinsic Correlation(TDIC) method. NAMEMD algorithm is a fully data-driven approach designed for nonlinear and nonstationary multivariate signals, and is performed to decompose multivariate signals into a collection of channels of Intrinsic Mode Functions (IMFs). TDIC method is an EMD-based method using a set of sliding window sizes to quantify localized correlation coefficients for multiscale signals. With the alignment property and quasi-dyadic filter bank of NAMEMD algorithm, one is able to produce same number of IMFs for all variables and estimates the cross correlation in a more accurate way. The performance of spectral representation of NAMEMD-HSA method is compared with Complementary Empirical Mode Decomposition/ Hilbert Spectral Analysis (CEEMD-HSA) and Wavelet Analysis. The nature of NAMAMD-based TDICC analysis is then compared with CEEMD-based TDIC analysis and the traditional correlation analysis.

Environmental factors associated with Crohn's disease in India.

PubMed

Pugazhendhi, Srinivasan; Sahu, Manoj Kumar; Subramanian, Venkataraman; Pulimood, Anna; Ramakrishna, Balakrishnan S

2011-12-01

The frequency of diagnosis of Crohn's disease (CD) in India is increasing. This case-control study was designed to detect associations of environmental and dietary factors with the diagnosis of CD. In 200 consecutive patients with CD and 200 control subjects without gastrointestinal disease, environmental hygiene exposures in childhood and in the past one year, and dietary preferences were recorded using a questionnaire. Univariate and multivariate analyses were done. In univariate analysis, CD showed positive association with urban residence (at birth and current), availability of protected drinking water (childhood and current), availability of piped water in the house (childhood and current), and strict vegetarian dietary habit, and negative association with regular fish consumption and presence of cattle in the house compound. Multivariate analysis showed that regular fish consumption (OR 0.52, 95% CI 0.33-0.80, p = 0.003), and presence of cattle in the house compound currently (OR 0.57, 95% CI 0.35-0.92, p = 0.023) were significant protective associations, whereas use of safe drinking water was positively associated (OR 1.59, 95% CI 1.02-2.47, p = 0.042) with the disease. Occurrence of CD was associated with dietary and environmental exposures, which indicate that diet and hygiene may influence the development of this disease.

Effects of valproate on the carotid artery intima-media thickness in epileptics.

PubMed

Luo, Xinming; Zhang, Ming; Deng, Liying; Zhao, Jing

2015-01-01

The objective was to explore the effects of valproate (VPA) on the carotid artery intima-media thickness (CA-IMT) in epileptics. A total of 30 epileptic patients treated with VPA was included as disease group, while 33 healthy people who matched general basic demographic details were the control group. The IMTs of the left and right carotids of the both groups were measured, and the average CA-IMT was calculated. The IMT-related risk factors were acquired for the univariate and multivariate analysis. The bilateral carotid and average CA-IMTs of the disease group were significantly higher than the control group (P < 0.001). The multivariant gradual regressive analysis screened out two CA-IMT-related factors, namely the disease duration and the drug administration duration were positively correlated with the average CA-IMT. The epileptic patients with disease course of more than 3 years had much higher average CA-IMT than that of the epileptics with ≤3 years disease (P < 0.001). The average CA-IMT of the patients with VPA-administration duration >1 year was also higher than that of the patients with VPA-administration duration <1 year, while the difference was not statistically significant (P = 0.196). The average CA-IMT of the epileptic patients treated with VPA was higher than that of healthy people.

Longitudinal assessment of treatment effects on pulmonary ventilation using 1H/3He MRI multivariate templates

NASA Astrophysics Data System (ADS)

Tustison, Nicholas J.; Contrella, Benjamin; Altes, Talissa A.; Avants, Brian B.; de Lange, Eduard E.; Mugler, John P.

2013-03-01

The utitlity of pulmonary functional imaging techniques, such as hyperpolarized 3He MRI, has encouraged their inclusion in research studies for longitudinal assessment of disease progression and the study of treatment effects. We present methodology for performing voxelwise statistical analysis of ventilation maps derived from hyper­ polarized 3He MRI which incorporates multivariate template construction using simultaneous acquisition of IH and 3He images. Additional processing steps include intensity normalization, bias correction, 4-D longitudinal segmentation, and generation of expected ventilation maps prior to voxelwise regression analysis. Analysis is demonstrated on a cohort of eight individuals with diagnosed cystic fibrosis (CF) undergoing treatment imaged five times every two weeks with a prescribed treatment schedule.

Finger taps and constipation are closely related to symptoms of overactive bladder in male patients with Parkinson's disease.

PubMed

Tsujimura, Akira; Yamamoto, Yoichi; Sakoda, Saburo; Okuda, Hidenobu; Yamamoto, Keisuke; Fukuhara, Shinichiro; Yoshioka, Iwao; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio

2014-01-01

To assess which motor and non-motor symptoms are closely related to overactive bladder severity in male patients with Parkinson's disease. A total of 160 male patients (mean age 71.4 ± 8.2 years) diagnosed with Parkinson's disease were included in the present study at Osaka University and affiliated hospitals. The severity of Parkinson's disease was classified as stage 3, 4 or 5 based on the Hoehn and Yahr staging system. Disease duration was 8.9 ± 5.1 years. Age, seven items from the Unified Parkinson's Disease Rating Scale motor section part III and three non-motor symptoms were assessed by multivariate analysis for their impact on the overactive bladder symptom score, a specific questionnaire for overactive bladder. Overactive bladder symptom score was significantly higher in the group with severe motor symptoms related to finger taps and gait than in the group with mild motor symptoms related to these two factors. Furthermore, overactive bladder symptom score of patients with erectile dysfunction and constipation was significantly higher than that in patients without these symptoms. Multivariate analysis identified only finger taps and constipation as factors independently associated with overactive bladder symptom score. Although a study on a larger scale is required to further assess the association of Parkinson's disease symptoms with overactive bladder symptom score, information on finger taps and severity of constipation should be obtained when assessing urological patients with Parkinson's disease. © 2013 The Japanese Urological Association.

Multivariate meta-analysis: a robust approach based on the theory of U-statistic.

PubMed

Ma, Yan; Mazumdar, Madhu

2011-10-30

Meta-analysis is the methodology for combining findings from similar research studies asking the same question. When the question of interest involves multiple outcomes, multivariate meta-analysis is used to synthesize the outcomes simultaneously taking into account the correlation between the outcomes. Likelihood-based approaches, in particular restricted maximum likelihood (REML) method, are commonly utilized in this context. REML assumes a multivariate normal distribution for the random-effects model. This assumption is difficult to verify, especially for meta-analysis with small number of component studies. The use of REML also requires iterative estimation between parameters, needing moderately high computation time, especially when the dimension of outcomes is large. A multivariate method of moments (MMM) is available and is shown to perform equally well to REML. However, there is a lack of information on the performance of these two methods when the true data distribution is far from normality. In this paper, we propose a new nonparametric and non-iterative method for multivariate meta-analysis on the basis of the theory of U-statistic and compare the properties of these three procedures under both normal and skewed data through simulation studies. It is shown that the effect on estimates from REML because of non-normal data distribution is marginal and that the estimates from MMM and U-statistic-based approaches are very similar. Therefore, we conclude that for performing multivariate meta-analysis, the U-statistic estimation procedure is a viable alternative to REML and MMM. Easy implementation of all three methods are illustrated by their application to data from two published meta-analysis from the fields of hip fracture and periodontal disease. We discuss ideas for future research based on U-statistic for testing significance of between-study heterogeneity and for extending the work to meta-regression setting. Copyright © 2011 John Wiley & Sons, Ltd.

The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus.

PubMed

Taraborelli, M; Leuenberger, L; Lazzaroni, M G; Martinazzi, N; Zhang, W; Franceschini, F; Salmon, J; Tincani, A; Erkan, D

2016-10-01

The objective of this study was to assess the contribution of clinically significant antiphospholipid antibodies (aPL) to organ damage in systemic lupus erythematosus (SLE). Patients with disease duration of less than 10 years and at least 5 years of follow-up were identified from two SLE registries. A clinically significant antiphospholipid antibody (aPL) profile was defined as: positive lupus anticoagulant, anticardiolipin IgG/M ≥ 40 G phospholipid units (GPL)/M phospholipid units (MPL), and/or anti-β2-glycoprotein-I IgG/M ≥ 99th percentile on two or more occasions, at least 12 weeks apart. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Univariate and multivariate analysis compared SLE patients with and without SDI increase during a 15-year follow-up. Among 262 SLE patients, 33% had a clinically significant aPL profile, which was associated with an increased risk of organ damage accrual during a 5-year follow-up in univariate analysis, and during a 15-year follow-up in the multivariate analysis adjusting for age, gender, race, disease duration at registry entry, and time. In the multivariate analysis, older age at diagnosis and male gender were also associated with SDI increase at each time point. A clinically significant aPL profile is associated with an increased risk of organ damage accrual during a 15-year follow-up in SLE patients. © The Author(s) 2016.

HER-2/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer

PubMed Central

Roses, Robert E.; Paulson, E. Carter; Sharma, Anupama; Schueller, Jeanne E.; Nisenbaum, Harvey; Weinstein, Susan; Fox, Kevin R.; Zhang, Paul J.; Czerniecki, Brian J.

2009-01-01

The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in situ (DCIS) lesions have yet to be clearly elucidated; this despite the more frequent expression of HER2 in high-grade DCIS lesions compared with invasive cancers. We hypothesized that HER2 overexpression in DCIS is associated with more rapid progression to invasive disease. Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate analysis and a multivariate logistic regression were done to determine whether estrogen receptor, progesterone receptor, or HER2 status, comedo necrosis, nuclear grade, lesion size, or patient age predicted the presence of associated invasive disease in patients with DCIS. Invasive foci were found in association with HER2 overexpressing DCIS at a higher frequency than with DCIS that did not overexpress HER2. Although high nuclear grade, large lesion size, and HER2 overexpression were all associated with the presence of invasive disease on univariate analysis, HER2 was the only significant predictor for the presence of invasive disease after multivariate adjustment (odds ratio, 6.4; P = 0.01). These data indicate that HER2 overexpression in DCIS lesions predicts the presence of invasive foci in patients with DCIS and suggest that targeting of HER2 in an early disease setting may forestall or prevent disease progression. PMID:19383888

Risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors.

PubMed

Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2014-09-01

The aim of this study was to identify risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors (BOTs). We performed a retrospective review of all patients treated and followed for BOTs between 1996 and 2011. Multivariate Cox proportional hazards model analysis was performed to identify independent risk factors for progression to invasive carcinoma. A total of 364 patients were identified. During the median follow-up of 53.8 months, 31 patients (8.5%) developed recurrent disease: 12 (3.3%) had recurrent disease with progression to invasive carcinoma, and 19 (5.2%) had recurrent disease with borderline histology. Disease-related deaths (7/364; 1.7%) were observed only in patients with progression to invasive carcinoma. The multivariate analysis showed that independent risk factors for progression to invasive carcinoma were advanced disease stage (hazard ratio [HR], 5.59; P = 0.005), age 65 years or older (HR, 5.13; P = 0.037), and the presence of microinvasion (HR, 3.71; P = 0.047). These 3 factors were also independently related to overall survival. Although patients with BOTs have an excellent prognosis, the risk of progression to invasive carcinoma and thereby death remains. Therefore, physicians should pay closer attention to BOT patients with these risk factors (ie, advanced disease stage, old age, and microinvasion), and more careful surveillance for progression to invasive carcinoma is needed.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

2016-10-01

To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

The International Scoring System (ISS) for multiple myeloma remains a robust prognostic tool independently of patients' renal function.

PubMed

Dimopoulos, M A; Kastritis, E; Michalis, E; Tsatalas, C; Michael, M; Pouli, A; Kartasis, Z; Delimpasi, S; Gika, D; Zomas, A; Roussou, M; Konstantopoulos, K; Parcharidou, A; Zervas, K; Terpos, E

2012-03-01

The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load. In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria. Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day. ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction.

Risk prediction for myocardial infarction via generalized functional regression models.

PubMed

Ieva, Francesca; Paganoni, Anna M

2016-08-01

In this paper, we propose a generalized functional linear regression model for a binary outcome indicating the presence/absence of a cardiac disease with multivariate functional data among the relevant predictors. In particular, the motivating aim is the analysis of electrocardiographic traces of patients whose pre-hospital electrocardiogram (ECG) has been sent to 118 Dispatch Center of Milan (the Italian free-toll number for emergencies) by life support personnel of the basic rescue units. The statistical analysis starts with a preprocessing of ECGs treated as multivariate functional data. The signals are reconstructed from noisy observations. The biological variability is then removed by a nonlinear registration procedure based on landmarks. Thus, in order to perform a data-driven dimensional reduction, a multivariate functional principal component analysis is carried out on the variance-covariance matrix of the reconstructed and registered ECGs and their first derivatives. We use the scores of the Principal Components decomposition as covariates in a generalized linear model to predict the presence of the disease in a new patient. Hence, a new semi-automatic diagnostic procedure is proposed to estimate the risk of infarction (in the case of interest, the probability of being affected by Left Bundle Brunch Block). The performance of this classification method is evaluated and compared with other methods proposed in literature. Finally, the robustness of the procedure is checked via leave-j-out techniques. © The Author(s) 2013.

Predictive model for falling in Parkinson disease patients.

PubMed

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Montesinos, Rosa; Castro-Suarez, Sheila; Cuenca-Alfaro, Jose; Cortijo, Patricia

2016-12-01

Falls are a common complication of advancing Parkinson's disease (PD). Although numerous risk factors are known, reliable predictors of future falls are still lacking. The aim of this study was to develop a multivariate model to predict falling in PD patients. Prospective cohort with forty-nine PD patients. The area under the receiver-operating characteristic curve (AUC) was calculated to evaluate predictive performance of the purposed multivariate model. The median of PD duration and UPDRS-III score in the cohort was 6 years and 24 points, respectively. Falls occurred in 18 PD patients (30%). Predictive factors for falling identified by univariate analysis were age, PD duration, physical activity, and scores of UPDRS motor, FOG, ACE, IFS, PFAQ and GDS ( p -value < 0.001), as well as fear of falling score ( p -value = 0.04). The final multivariate model (PD duration, FOG, ACE, and physical activity) showed an AUC = 0.9282 (correctly classified = 89.83%; sensitivity = 92.68%; specificity = 83.33%). This study showed that our multivariate model have a high performance to predict falling in a sample of PD patients.

Hypothyroidism and Glaucoma in The United States

PubMed Central

Kakigi, Caitlin; Kasuga, Toshimitsu; Wang, Sophia Y.; Singh, Kuldev; Hiratsuka, Yoshimune; Murakami, Akira; Lin, Shan C.

2015-01-01

Purpose To investigate the association between hypothyroidism and glaucomatous disease. Methods This cross-sectional study included all subjects above the age of 40 years from two nationwide surveys: the 2008 National Health Interview Survey (NHIS) as well as the 2007 and 2008 National Health and Nutrition Examination Survey (NHANES). The presence or absence of glaucoma, thyroid disease and other demographic and health-related information including comorbidities was ascertained via interview. Blood samples were collected from NHANES subjects and analyzed for thyrotropin (TSH). Results A total of 13,599 and 3,839 NHIS and NHANES participants respectively were analyzed to assess for a possible relationship between self-reported glaucoma, and self-reported hypothyroidism as well as self-reported thyroid disease. The unadjusted odds ratio (OR) for NHIS showed a significant association between self-reported glaucoma and self-reported hypothyroidism (OR 1.46, 95% confidence interval [CI] 1.07-1.99). Multivariate logistic regression analysis adjusted for age, gender, race, comorbidities, and health-related behavior, however, showed no association between self-reported glaucoma and hypothyroidism or thyroid disease in both surveys (OR 1.60, 95%CI 0.87-2.95 for NHIS; OR 1.05, 95%CI 0.59-1.88 for NHANES). Conclusion A previously reported association between hypothyroidism and glaucomatous disease was not confirmed in two large U.S. health survey populations. While such an association was noted in the univariate analysis for the NHIS survey, such a relationship was not found in the multivariate analysis after adjustment for potential confounding variables. PMID:26230664

Prognostic Factors Influencing the Outcome of 64 Consecutive Patients Undergoing Surgery for Metastatic Melanoma of the Spine.

PubMed

Sellin, Jonathan N; Gressot, Loyola V; Suki, Dima; St Clair, Eric G; Chern, Joshua; Rhines, Laurence D; McCutcheon, Ian E; Rao, Ganesh; Tatsui, Claudio E

2015-09-01

Melanoma metastases to the spine remain a challenge for neurosurgeons. To identify factors associated with survival in a series of patients who underwent spinal surgery for metastatic melanoma. We retrospectively reviewed all patients (n = 64) who received surgical intervention for melanoma metastases to the spine at the University of Texas MD Anderson Cancer Center between July 1993 and March 2012. No patients were excluded from the study, and vital status data were available for all patients. Median overall survival was 5.7 months (95% confidence interval, 2.7-28.7). On univariate survival analysis, diagnosis of spinal metastasis after prior diagnosis of systemic metastasis, higher total spinal disease burden (including but not exclusive to the operative site), presence of progressive systemic disease at the moment of spine surgery, and postoperative complications were associated with poorer overall survival, whereas the presence of only bone metastasis at the moment of surgery was associated with improved overall survival. On multivariate survival analysis, both progressive systemic disease at the moment of spine surgery and total spinal disease burden of ≥3 vertebral levels were significantly associated with worse overall survival (hazard ratio, 6.00; 95% confidence interval, 3.19-11.28; P < .001; and hazard ratio, 2.87; 95% confidence interval, 1.62-5.07; P < .001, respectively). On multivariate analysis, involvement of ≥3 vertebral bodies and progressive systemic disease were associated with worse overall survival. Consideration of these factors should influence surgical decision making in this patient population.

[Relationship between quality of life and disability level in patients with occupational disease].

PubMed

Li, Hongmei; Lin, Mingjing; Zhang, Wenwen; Li, Jing; Zou, Jianfang

2015-10-01

To investigate the relationship between the quality of life (QOL) and disability level in patients with occupational disease and to investigate the influencing factors for QOL. A total of 255 patients with occupational disease were selected from three specialized hospitals dedicated to occupational disease and the department of occupational medicine of one comprehensive hospital using cluster sampling from December 2013 to May 2014. A survey was carried out using WHOQOL-BREF and general questionnaire (including disability level), and statistical analysis was also performed using t test, F test, analysis of variance, and multivariate stepwise regression analysis. The QOL scores of patients with occupational diseases, from high to low, were social domain (11.48 ± 2.86), psychological domain (10.60 ± 2.28), physiological domain (10.54 ± 1.65), and environmental domain (10.50 ± 2.55), scores of which were significantly lower than the normal levels (P<0.05). QOL showed no significant differences between patients with occupational diseases of different disability levels (P>0.05). Also, QOL showed no significant differences between stage I, II and III patients with pneumoconiosis (P>0.05). The patients with pneumoconiosis were divided into mild, moderate, and severe groups, and the QOL scores of patients with mild pneumoconiosis in psychological and environmental domains were significantly higher than those of the patients with moderate or severe pneumoconiosis (P< 0.05). Patients with occupational poisoning was divided into mild, moderate and severe groups, and the three groups showed no significant differences in QOL score (P>0.05). Multivariate regression analysis showed that the QOL score of each domain was mainly influenced by the degree of lung injury, complications, course of disease, age of onset, income, and employment status. The QOL of patients with occupational disease is significantly reduced, and disability level cannot accurately reflect their QOL. The treatment of patients with occupational disease should focus on their complications, and at the same time QOL should also be improved.

The classification of secondary colorectal liver cancer in human biopsy samples using angular dispersive x-ray diffraction and multivariate analysis

NASA Astrophysics Data System (ADS)

Theodorakou, Chrysoula; Farquharson, Michael J.

2009-08-01

The motivation behind this study is to assess whether angular dispersive x-ray diffraction (ADXRD) data, processed using multivariate analysis techniques, can be used for classifying secondary colorectal liver cancer tissue and normal surrounding liver tissue in human liver biopsy samples. The ADXRD profiles from a total of 60 samples of normal liver tissue and colorectal liver metastases were measured using a synchrotron radiation source. The data were analysed for 56 samples using nonlinear peak-fitting software. Four peaks were fitted to all of the ADXRD profiles, and the amplitude, area, amplitude and area ratios for three of the four peaks were calculated and used for the statistical and multivariate analysis. The statistical analysis showed that there are significant differences between all the peak-fitting parameters and ratios between the normal and the diseased tissue groups. The technique of soft independent modelling of class analogy (SIMCA) was used to classify normal liver tissue and colorectal liver metastases resulting in 67% of the normal tissue samples and 60% of the secondary colorectal liver tissue samples being classified correctly. This study has shown that the ADXRD data of normal and secondary colorectal liver cancer are statistically different and x-ray diffraction data analysed using multivariate analysis have the potential to be used as a method of tissue classification.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

PubMed

Mooney, Peter D; Leeds, John S; Libzo, Nafan; Sidhu, Reina; Evans, Kate E; Hall, Emma J; Jandu, Veerinder S; Hopper, Andrew D; Basumani, Pandurangan; Dear, Keith L; McAlindon, Mark E; Sanders, David S

2014-01-01

Coeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics. Unselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors. 4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk. Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

PubMed

Fridman, Eran; Na'ara, Shorook; Agarwal, Jaiprakash; Amit, Moran; Bachar, Gideon; Villaret, Andrea Bolzoni; Brandao, Jose; Cernea, Claudio R; Chaturvedi, Pankaj; Clark, Jonathan; Ebrahimi, Ardalan; Fliss, Dan M; Jonnalagadda, Sashikanth; Kohler, Hugo F; Kowalski, Luiz P; Kreppel, Matthias; Liao, Chun-Ta; Patel, Snehal G; Patel, Raj P; Robbins, K Thomas; Shah, Jatin P; Shpitzer, Thomas; Yen, Tzu-Chen; Zöller, Joachim E; Gil, Ziv

2018-05-14

Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

PubMed

Zhou, Yan; Wang, Pei; Wang, Xianlong; Zhu, Ji; Song, Peter X-K

2017-01-01

The multivariate regression model is a useful tool to explore complex associations between two kinds of molecular markers, which enables the understanding of the biological pathways underlying disease etiology. For a set of correlated response variables, accounting for such dependency can increase statistical power. Motivated by integrative genomic data analyses, we propose a new methodology-sparse multivariate factor analysis regression model (smFARM), in which correlations of response variables are assumed to follow a factor analysis model with latent factors. This proposed method not only allows us to address the challenge that the number of association parameters is larger than the sample size, but also to adjust for unobserved genetic and/or nongenetic factors that potentially conceal the underlying response-predictor associations. The proposed smFARM is implemented by the EM algorithm and the blockwise coordinate descent algorithm. The proposed methodology is evaluated and compared to the existing methods through extensive simulation studies. Our results show that accounting for latent factors through the proposed smFARM can improve sensitivity of signal detection and accuracy of sparse association map estimation. We illustrate smFARM by two integrative genomics analysis examples, a breast cancer dataset, and an ovarian cancer dataset, to assess the relationship between DNA copy numbers and gene expression arrays to understand genetic regulatory patterns relevant to the disease. We identify two trans-hub regions: one in cytoband 17q12 whose amplification influences the RNA expression levels of important breast cancer genes, and the other in cytoband 9q21.32-33, which is associated with chemoresistance in ovarian cancer. © 2016 WILEY PERIODICALS, INC.

Comparative evaluation of H&H and WFNS grading scales with modified H&H (sans systemic disease): A study on 1000 patients with subarachnoid hemorrhage.

PubMed

Aggarwal, Ashish; Dhandapani, Sivashanmugam; Praneeth, Kokkula; Sodhi, Harsimrat Bir Singh; Pal, Sudhir Singh; Gaudihalli, Sachin; Khandelwal, N; Mukherjee, Kanchan K; Tewari, M K; Gupta, Sunil Kumar; Mathuriya, S N

2018-01-01

The comparative studies on grading in subarachnoid hemorrhage (SAH) had several limitations such as the unclear grading of Glasgow Coma Scale 15 with neurological deficits in World Federation of Neurosurgical Societies (WFNS), and the inclusion of systemic disease in Hunt and Hess (H&H) scales. Their differential incremental impacts and optimum cut-off values for unfavourable outcome are unsettled. This is a prospective comparison of prognostic impacts of grading schemes to address these issues. SAH patients were assessed using WFNS, H&H (including systemic disease), modified H&H (sans systemic disease) and followed up with Glasgow Outcome Score (GOS) at 3 months. Their performance characteristics were analysed as incremental ordinal variables and different grading scale dichotomies using rank-order correlation, sensitivity, specificity, positive predictive value, negative predictive value, Youden's J and multivariate analyses. A total of 1016 patients were studied. As univariate incremental variable, H&H sans systemic disease had the best negative rank-order correlation coefficient (-0.453) with respect to lower GOS (p < 0.001). As univariate dichotomized category, WFNS grades 3-5 had the best performance index of 0.39 to suggest unfavourable GOS with a specificity of 89% and sensitivity of 51%. In multivariate incremental analysis, H&H sans systemic disease had the greatest adjusted incremental impact of 0.72 (95% confidence interval (CI) 0.54-0.91) against a lower GOS as compared to 0.6 (95% CI 0.45-0.74) and 0.55 (95% CI 0.42-0.68) for H&H and WFNS grades, respectively. In multivariate categorical analysis, H&H grades 4-5 sans systemic disease had the greatest impact on unfavourable GOS with an adjusted odds ratio of 6.06 (95% CI 3.94-9.32). To conclude, H&H grading sans systemic disease had the greatest impact on unfavourable GOS. Though systemic disease is an important prognostic factor, it should be considered distinctly from grading. Appropriate cut-off values suggesting unfavourable outcome for H&H and WFNS were 4-5 and 3-5, respectively, indicating the importance of neurological deficits in addition to level of consciousness.

Spectral discrimination of serum from liver cancer and liver cirrhosis using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Yang, Tianyue; Li, Xiaozhou; Yu, Ting; Sun, Ruomin; Li, Siqi

2011-07-01

In this paper, Raman spectra of human serum were measured using Raman spectroscopy, then the spectra was analyzed by multivariate statistical methods of principal component analysis (PCA). Then linear discriminant analysis (LDA) was utilized to differentiate the loading score of different diseases as the diagnosing algorithm. Artificial neural network (ANN) was used for cross-validation. The diagnosis sensitivity and specificity by PCA-LDA are 88% and 79%, while that of the PCA-ANN are 89% and 95%. It can be seen that modern analyzing method is a useful tool for the analysis of serum spectra for diagnosing diseases.

Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

PubMed

Fan, Bo; Hu, Bin; Yuan, Qingmin; Wen, Shuang; Liu, Tianqing; Bai, Shanshan; Qi, Xiaofeng; Wang, Xin; Yang, Deyong; Sun, Xiuzhen; Song, Xishuang

2017-07-01

Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.

Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults.

PubMed

Moreno Cervantes, C; Mimenza Alvarado, A; Aguilar Navarro, S; Alvarado Ávila, P; Gutiérrez Gutiérrez, L; Juárez Arellano, S; Ávila Funes, J A

2017-06-01

Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) CONCLUSIONS: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Single Marital Status and Infectious Mortality in Women With Cervical Cancer in the United States.

PubMed

Machida, Hiroko; Eckhardt, Sarah E; Castaneda, Antonio V; Blake, Erin A; Pham, Huyen Q; Roman, Lynda D; Matsuo, Koji

2017-10-01

Unmarried status including single marital status is associated with increased mortality in women bearing malignancy. Infectious disease weights a significant proportion of mortality in patients with malignancy. Here, we examined an association of single marital status and infectious mortality in cervical cancer. This is a retrospective observational study examining 86,555 women with invasive cervical cancer identified in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Characteristics of 18,324 single women were compared with 38,713 married women in multivariable binary logistic regression models. Propensity score matching was performed to examine cumulative risk of all-cause and infectious mortality between the 2 groups. Single marital status was significantly associated with young age, black/Hispanic ethnicity, Western US residents, uninsured status, high-grade tumor, squamous histology, and advanced-stage disease on multivariable analysis (all, P < 0.05). In a prematched model, single marital status was significantly associated with increased cumulative risk of all-cause mortality (5-year rate: 32.9% vs 29.7%, P < 0.001) and infectious mortality (0.5% vs 0.3%, P < 0.001) compared with the married status. After propensity score matching, single marital status remained an independent prognostic factor for increased cumulative risk of all-cause mortality (adjusted hazards ratio [HR], 1.15; 95% confidence interval [CI], 1.11-1.20; P < 0.001) and those of infectious mortality on multivariable analysis (adjusted HR, 1.71; 95% CI, 1.27-2.32; P < 0.001). In a sensitivity analysis for stage I disease, single marital status remained significantly increased risk of infectious mortality after propensity score matching (adjusted HR, 2.24; 95% CI, 1.34-3.73; P = 0.002). Single marital status was associated with increased infectious mortality in women with invasive cervical cancer.

Multivariate Analysis of Factors Associated with the Koebner Phenomenon in Vitiligo: An Observational Study of 381 Patients

PubMed Central

Khurrum, Huma; Bedaiwi, Khalid M.; AlBalahi, Naif Meshael

2017-01-01

Background The Koebner phenomenon (KP) is a common entity observed in dermatological disorders. The reported incidence of KP in vitiligo varies widely. Although the KP is frequently observed in patients with viltiligo, the associated factors with KP has not been established yet. Objective The aim is to estimate the prevalence of KP in vitiligo patients and to investigate the associated factors with KP among vitiligo characteristics. Methods A cross-sectional observational study was conducted using 381 vitiligo patients. Demographic and clinical information was obtained via the completion of Vitiligo European Task Force (VETF) questionnaires. Patients with positive history of KP were extracted from this vitiligo database. Multivariate analysis was performed to assess associations with KP. Results The median age of cases was 24 years (range, 0.6~76). In total, 237 of the patients were male (62.2%). Vitiligo vulgaris was the most common type observed (152/381, 39.9%). Seventy-two percent (274/381) patients did not exhibit KP, whereas 28.1% (107/381) of patients exhibited this condition. Multivariable analysis showed the following to be independent factors with KP in patients with vitiligo: the progressive disease (odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.17~2.92; p=0.041), disease duration longer than 5 years (OR, 1.92; 95% CI, 1.22~2.11; p=0.003), and body surface area more than 2% (OR, 2.20; 95% CI, 1.26~3.24; p<0.001). Conclusion Our results suggest that KP may be used to evaluate disease activity and investigate different associations between the clinical profile and course of vitiligo. Further studies are needed to predict the relationship between KP and responsiveness to therapy. PMID:28566906

Employment after heart transplantation among adults with congenital heart disease.

PubMed

Tumin, Dmitry; Chou, Helen; Hayes, Don; Tobias, Joseph D; Galantowicz, Mark; McConnell, Patrick I

2017-12-01

Adults with congenital heart disease may require heart transplantation for end-stage heart failure. Whereas heart transplantation potentially allows adults with congenital heart disease to resume their usual activities, employment outcomes in this population are unknown. Therefore, we investigated the prevalence and predictors of work participation after heart transplantation for congenital heart disease. Retrospective review of a prospective registry. United Network for Organ Sharing registry of transplant recipients in the United States. Adult recipients of first-time heart transplantation with a primary diagnosis of congenital heart disease, performed between 2004 and 2015. None. Employment status reported by transplant centers at required follow-up intervals up to 5 y posttransplant. Among 470 patients included in the analysis (mean follow-up: 5 ± 3 y), 127 (27%) worked after transplant, 69 (15%) died before beginning or returning to work, and 274 (58%) survived until censoring, but did not participate in paid work. Multivariable competing-risks regression analysis examined characteristics associated with posttransplant employment, accounting for mortality as a competing outcome. In descriptive and multivariable analysis, pretransplant work participation was associated with a greater likelihood of posttransplant employment, while the use of Medicaid insurance at the time of transplant was associated with a significantly lower likelihood of working after transplant (subhazard ratio compared to private insurance: 0.55; 95% confidence interval: 0.32, 0.95; P = .032). Employment was rare after heart transplantation for congenital heart disease, and was significantly less common than in the broader population of adults with congenital heart disease. Differences in return to work were primarily related to pretransplant employment and the use of public insurance, rather than clinical characteristics. © 2017 Wiley Periodicals, Inc.

Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla-oral versus sinus.

PubMed

Bobinskas, A M; Wiesenfeld, D; Chandu, A

2014-02-01

The maxilla may be affected by squamous cell carcinoma (SCC) from both oral and sinus sites. We sought to determine whether the site of origin of the maxillary tumour, oral as compared to sinus, influences survival. Univariate Kaplan-Meier and multivariate Cox proportional hazard models analysis of 58 patients with SCC involving the maxilla, treated with curative intent, was conducted. The overall 5-year disease-free survival for the group was 41.7%. Five-year disease-free survival for oral subsite SCC was 56.8%, while for sinus subsite was only 21.6%. Univariate analysis found SCC of sinus origin to be associated with a poorer prognosis, however this was not confirmed on multivariate analysis. T-stage and positive margins were found to be the only independent risk factors. For SCC of the maxilla, sinus origin of the tumour per se does not confer a poorer prognosis; however, as a result of the complex anatomy of the midface, these tumours can present at an advanced stage, while surgical control of the disease can be more difficult, especially posteriorly. Tumour size and positive margins were the determinants of a poor prognosis in this group of patients with maxillary SCC. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients.

PubMed

Bryant, A; Nivison-Smith, I; Pillai, E S; Kennedy, G; Kalff, A; Ritchie, D; George, B; Hertzberg, M; Patil, S; Spencer, A; Fay, K; Cannell, P; Berkahn, L; Doocey, R; Spearing, R; Moore, J

2014-01-01

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years (18-68). In all, 234 patients had myeloid malignancies, with AML (n=166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n=64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLA-identical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P=0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

[Risk factors of benign anastomostic strictures after esophagectomy with cervical reconstruction].

PubMed

Zhong, Sheng; Wu, Qinquan; Sun, Su'an; Gu, Biao; Zhao, Ming; Chen, Qiyou

2014-09-01

To identify the risk factors of benign cervical anastomotic strictures after esophagectomy. Clinical data of 946 esophageal cancer patients undergoing esophagectomy with cervical anastomosis between 2003 and 2012 were analyzed retrospectively. Benign stricture was defined as dysphagia for which endoscopic dilation of the anastomosis was needed. Histologically proven malignant stricture was not regarded as benign stricture. χ(2) test and logistic regression model were used for univariate and multivariate analysis respectively. A total of 146 patients(16.5%) developed benign stricture during follow-up. Univariate analysis showed that the patients with cardiovascular disease (P=0.001), diabetes mellitus(P=0.041), gastric tube reconstruction(P=0.050), end-to-end anastomosis (P=0.013), or postoperative anastomotic leakage(P=0.008) had higher stricture rate. Multivariate analysis revealed that cardiovascular disease(P=0.004), gastric tube reconstruction (P=0.026), end-to-end anastomosis(P=0.043), and postoperative anastomotic leakage(P=0.001) were independently predictive factors for development of benign stricture. The benign cervical stricture rate after esophagetomy with cervical gastric anastomosis is quite high. In order to prevent benign stricture formation, end-to-end anastomosis should be avoid. Blood pressure should be controlled for those with cardiovascular disease. Endoscopic dilation in an earlier stage postoperatively should be considered for those who develop anastomotic leakage.

Oral pathology follow-up by means of micro-Raman spectroscopy on tissue and blood serum samples: an application of wavelet and multivariate data analysis

NASA Astrophysics Data System (ADS)

Delfino, I.; Camerlingo, C.; Zenone, F.; Perna, G.; Capozzi, V.; Cirillo, N.; Gaeta, G. M.; De Mol, E.; Lepore, M.

2009-02-01

Pemphigus vulgaris (PV) is a potentially fatal autoimmune disease that cause blistering of the skin and oral cavity. It is characterized by disruption of cell-cell adhesion within the suprabasal layers of epithelium, a phenomenon termed acantholysis Patients with PV develop IgG autoantibodies against normal constituents of the intercellular substance of keratinocytes. The mechanisms by which such autoantibodies induce blisters are not clearly understood. The qualitative analysis of such effects provides important clues in the search for a specific diagnosis, and the quantitative analysis of biochemical abnormalities is important in measuring the extent of the disease process, designing therapy and evaluating the efficacy of treatment. Improved diagnostic techniques could permit the recognition of more subtle forms of disease and reveal incipient lesions clinically unapparent, so that progression of potentially severe forms could be reversed with appropriate treatment. In this paper, we report the results of our micro-Raman spectroscopy study on tissue and blood serum samples from ill, recovered and under therapy PV patients. The complexity of the differences among their characteristic Raman spectra has required a specific strategy to obtain reliable information on the illness stage of the patients For this purpose, wavelet techniques and advanced multivariate analysis methods have been developed and applied to the experimental Raman spectra. Promising results have been obtained.

Multivariate generalized multifactor dimensionality reduction to detect gene-gene interactions

PubMed Central

2013-01-01

Background Recently, one of the greatest challenges in genome-wide association studies is to detect gene-gene and/or gene-environment interactions for common complex human diseases. Ritchie et al. (2001) proposed multifactor dimensionality reduction (MDR) method for interaction analysis. MDR is a combinatorial approach to reduce multi-locus genotypes into high-risk and low-risk groups. Although MDR has been widely used for case-control studies with binary phenotypes, several extensions have been proposed. One of these methods, a generalized MDR (GMDR) proposed by Lou et al. (2007), allows adjusting for covariates and applying to both dichotomous and continuous phenotypes. GMDR uses the residual score of a generalized linear model of phenotypes to assign either high-risk or low-risk group, while MDR uses the ratio of cases to controls. Methods In this study, we propose multivariate GMDR, an extension of GMDR for multivariate phenotypes. Jointly analysing correlated multivariate phenotypes may have more power to detect susceptible genes and gene-gene interactions. We construct generalized estimating equations (GEE) with multivariate phenotypes to extend generalized linear models. Using the score vectors from GEE we discriminate high-risk from low-risk groups. We applied the multivariate GMDR method to the blood pressure data of the 7,546 subjects from the Korean Association Resource study: systolic blood pressure (SBP) and diastolic blood pressure (DBP). We compare the results of multivariate GMDR for SBP and DBP to the results from separate univariate GMDR for SBP and DBP, respectively. We also applied the multivariate GMDR method to the repeatedly measured hypertension status from 5,466 subjects and compared its result with those of univariate GMDR at each time point. Results Results from the univariate GMDR and multivariate GMDR in two-locus model with both blood pressures and hypertension phenotypes indicate best combinations of SNPs whose interaction has significant association with risk for high blood pressures or hypertension. Although the test balanced accuracy (BA) of multivariate analysis was not always greater than that of univariate analysis, the multivariate BAs were more stable with smaller standard deviations. Conclusions In this study, we have developed multivariate GMDR method using GEE approach. It is useful to use multivariate GMDR with correlated multiple phenotypes of interests. PMID:24565370

Damage in the Multiethnic Malaysian Systemic Lupus Erythematosus (SLE) Cohort: Comparison with Other Cohorts Worldwide

PubMed Central

Shaharir, Syahrul Sazliyana; Hussein, Heselynn; Rajalingham, Sakthiswary; Mohamed Said, Mohd Shahrir; Abdul Gafor, Abdul Halim; Mohd, Rozita; Mustafar, Ruslinda

2016-01-01

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease and despite the improvement in the survival in the past few decades, the morbidity due to disease damage remains significant. The objectives of this study were to investigate the disease damagepattern and determine the associated factors of damage in the multi-ethnic Malaysian SLE patients. We consecutively 424SLE patients who attended a consistent follow-up at the National University of Malaysia Medical Centre and Putrajaya Hospital were recruited. Disease damage was assessed using the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index (SDI) scores. Information on their demographics and disease characteristics were obtained from the clinical record. Univariate analysis was performed and the best model of independent predictors of disease damage was determined by multivariate logistic regression analysis. A total of 182 patients (42.9%) had disease damage (SDI ≥1). A significantly higher number of Indian patients had disease/organ damage and they predominantly developed steroid-induced diabetes mellitus (SDM). Patients with corticosteroid-induced osteoporosis (CIOP) were more likely to be Malayswhile majority of patients who developed malignancy were Chinese (p<0.05). In the univariate and multivariate analyses, disease damage was significantly associated with age, Indian ethnicity, lower mean cumulative C3 level, neuropsychiatry lupus (NPSLE), and antiphospholipid syndrome (APLS). Patients who had ever and early treatment with hydroxychloroquine(HCQ)were less likely to develop disease damage while more patients who had received oral prednisolone ≥1mg/kg daily over 2 weeks had disease damage (p<0.05). In conclusion, there were inter-ethnic differences in the damage pattern and risks among SLE patients. PMID:27846298

FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

PubMed

Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-22

Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

Multi-disease analysis of maternal antibody decay using non-linear mixed models accounting for censoring.

PubMed

Goeyvaerts, Nele; Leuridan, Elke; Faes, Christel; Van Damme, Pierre; Hens, Niel

2015-09-10

Biomedical studies often generate repeated measures of multiple outcomes on a set of subjects. It may be of interest to develop a biologically intuitive model for the joint evolution of these outcomes while assessing inter-subject heterogeneity. Even though it is common for biological processes to entail non-linear relationships, examples of multivariate non-linear mixed models (MNMMs) are still fairly rare. We contribute to this area by jointly analyzing the maternal antibody decay for measles, mumps, rubella, and varicella, allowing for a different non-linear decay model for each infectious disease. We present a general modeling framework to analyze multivariate non-linear longitudinal profiles subject to censoring, by combining multivariate random effects, non-linear growth and Tobit regression. We explore the hypothesis of a common infant-specific mechanism underlying maternal immunity using a pairwise correlated random-effects approach and evaluating different correlation matrix structures. The implied marginal correlation between maternal antibody levels is estimated using simulations. The mean duration of passive immunity was less than 4 months for all diseases with substantial heterogeneity between infants. The maternal antibody levels against rubella and varicella were found to be positively correlated, while little to no correlation could be inferred for the other disease pairs. For some pairs, computational issues occurred with increasing correlation matrix complexity, which underlines the importance of further developing estimation methods for MNMMs. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluating the predictive power of multivariate tensor-based morphometry in Alzheimer's disease progression via convex fused sparse group Lasso

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Gajawelli, Niharika; Zhou, Jiayu; Shi, Jie; Ye, Jieping; Wang, Yalin; Lepore, Natasha

2014-03-01

Prediction of Alzheimers disease (AD) progression based on baseline measures allows us to understand disease progression and has implications in decisions concerning treatment strategy. To this end we combine a predictive multi-task machine learning method1 with novel MR-based multivariate morphometric surface map of the hippocampus2 to predict future cognitive scores of patients. Previous work by Zhou et al.1 has shown that a multi-task learning framework that performs prediction of all future time points (or tasks) simultaneously can be used to encode both sparsity as well as temporal smoothness. They showed that this can be used in predicting cognitive outcomes of Alzheimers Disease Neuroimaging Initiative (ADNI) subjects based on FreeSurfer-based baseline MRI features, MMSE score demographic information and ApoE status. Whilst volumetric information may hold generalized information on brain status, we hypothesized that hippocampus specific information may be more useful in predictive modeling of AD. To this end, we applied Shi et al.2s recently developed multivariate tensor-based (mTBM) parametric surface analysis method to extract features from the hippocampal surface. We show that by combining the power of the multi-task framework with the sensitivity of mTBM features of the hippocampus surface, we are able to improve significantly improve predictive performance of ADAS cognitive scores 6, 12, 24, 36 and 48 months from baseline.

High performance computing enabling exhaustive analysis of higher order single nucleotide polymorphism interaction in Genome Wide Association Studies.

PubMed

Goudey, Benjamin; Abedini, Mani; Hopper, John L; Inouye, Michael; Makalic, Enes; Schmidt, Daniel F; Wagner, John; Zhou, Zeyu; Zobel, Justin; Reumann, Matthias

2015-01-01

Genome-wide association studies (GWAS) are a common approach for systematic discovery of single nucleotide polymorphisms (SNPs) which are associated with a given disease. Univariate analysis approaches commonly employed may miss important SNP associations that only appear through multivariate analysis in complex diseases. However, multivariate SNP analysis is currently limited by its inherent computational complexity. In this work, we present a computational framework that harnesses supercomputers. Based on our results, we estimate a three-way interaction analysis on 1.1 million SNP GWAS data requiring over 5.8 years on the full "Avoca" IBM Blue Gene/Q installation at the Victorian Life Sciences Computation Initiative. This is hundreds of times faster than estimates for other CPU based methods and four times faster than runtimes estimated for GPU methods, indicating how the improvement in the level of hardware applied to interaction analysis may alter the types of analysis that can be performed. Furthermore, the same analysis would take under 3 months on the currently largest IBM Blue Gene/Q supercomputer "Sequoia" at the Lawrence Livermore National Laboratory assuming linear scaling is maintained as our results suggest. Given that the implementation used in this study can be further optimised, this runtime means it is becoming feasible to carry out exhaustive analysis of higher order interaction studies on large modern GWAS.

The role of whole brain radiation therapy in the management of melanoma brain metastases

PubMed Central

2014-01-01

Background Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials. PMID:24954062

Occupational and Biomass Exposure in Chronic Obstructive Pulmonary Disease: Results of a Cross-Sectional Analysis of the On-Sint Study.

PubMed

López-Campos, José Luis; Fernández-Villar, Alberto; Calero-Acuña, Carmen; Represas-Represas, Cristina; López-Ramírez, Cecilia; Fernández, Virginia Leiro; Casamor, Ricard

2017-01-01

Although tobacco smoke is the main risk factor for chronic obstructive pulmonary disease (COPD), other inhaled toxics have also been associated with the disease. The present study analyzes data from exposure to these substances in a cohort of patients with COPD and assesses their impact on the clinical presentation of the disease. This is a cross-sectional analysis of the Clinical presentation, diagnosis and course of chronic obstructive pulmonary disease (On-Sint) study. All patients were smokers or ex-smokers as per protocol. In addition, during the inclusion visit patients were enquired about their occupational and biomass exposure history. The clinical features of patients with and without an added risk factor to tobacco were compared and those significant were entered in a multivariate logistic regression analysis, expressed as odds ratio (OR). The sample size was 1214 patients with COPD, of which 1012 (83.4%) had tobacco as the only risk factor and 202 (16.6%) had additional ones, mainly 174 (14.3%) with occupational gases and 32 (2.6%) with biomass exposure. The geographical distribution of this exposure showed a preference for the northern parts of the country and the East coast. The biomass exposure was rather low. Male gender (OR: 2.180), CAT score (OR: 1.036) and the use of long-term oxygen therapy (OR: 1.642) were associated with having an additional risk factor in the multivariate analysis. Occupational exposures are more common than biomass in Spain. COPD caused by tobacco plus other inhalants has some differential features and a more impaired quality of life. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

PubMed

Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2018-06-19

To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

Metabolic markers and ALT cutoff level for diagnosing nonalcoholic fatty liver disease: a community-based cross-sectional study.

PubMed

Miyake, Teruki; Kumagi, Teru; Hirooka, Masashi; Koizumi, Mitsuhito; Furukawa, Shinya; Ueda, Teruhisa; Tokumoto, Yoshio; Ikeda, Yoshio; Abe, Masanori; Kitai, Kohichiro; Hiasa, Yoichi; Matsuura, Bunzo; Onji, Morikazu

2012-06-01

Untreated nonalcoholic fatty liver disease (NAFLD) may progress to liver cirrhosis or failure and is associated with the development of hepatocellular carcinoma, diabetes, and cardiovascular disease. It is therefore essential to diagnose and treat NAFLD at an early stage. To assist in this effort, this retrospective study explored the risk factors for NAFLD, and derived new surrogates, a revised alanine aminotransferase (ALT) cutoff level and a novel NAFLD index, to identify previously undiagnosed cases of NAFLD. Using a community-based, cross-sectional design, the records of 6,370 Japanese subjects who had undergone at least 1 annual health check-up were reviewed for the identification of subjects meeting the diagnostic criteria for NAFLD and the variables associated with NAFLD for the estimation of ideal ALT cutoff levels. The results of multivariate analysis of the 1,346 subjects who met the diagnostic criteria for NAFLD confirmed that metabolic disease markers and a novel NAFLD index, using the variables derived from multivariate analysis, were also markers of NAFLD. The ALT cutoff levels for NAFLD diagnosis were estimated at 25 U/L for males and 17 U/L for females. ALT level and the novel NAFLD index were confirmed to be surrogate markers for NAFLD in addition to metabolic disease markers. The ALT cutoff level used in NAFLD diagnosis should be revised downward to identify subjects at risk of NAFLD to prevent NAFLD progression and the development of associated diseases.

Risk of Postoperative Complications Among Inflammatory Bowel Disease Patients Treated Preoperatively With Vedolizumab.

PubMed

Yamada, Akihiro; Komaki, Yuga; Patel, Nayan; Komaki, Fukiko; Aelvoet, Arthur S; Tran, Anthony L; Pekow, Joel; Dalal, Sushila; Cohen, Russell D; Cannon, Lisa; Umanskiy, Konstantin; Smith, Radhika; Hurst, Roger; Hyman, Neil; Rubin, David T; Sakuraba, Atsushi

2017-09-01

Vedolizumab is increasingly used to treat patients with ulcerative colitis (UC) and Crohn's disease (CD), however, its safety during the perioperative period remains unclear. We compared the 30-day postoperative complications among patients treated preoperatively with vedolizumab, anti-tumor necrosis factor (TNF)-α agents or non-biological therapy. The retrospective study cohort was comprised of patients receiving vedolizumab, anti-TNF-α agents or non-biological therapy within 4 weeks of surgery. The rates of 30-day postoperative complications were compared between groups using univariate and multivariate analysis. Propensity score-matched analysis was performed to compare the outcome between groups. Among 443 patients (64 vedolizumab, 129 anti-TNF-α agents, and 250 non-biological therapy), a total of 144 patients experienced postoperative complications (32%). In multivariate analysis, age >65 (odds ratio (OR) 3.56, 95% confidence interval (CI) 1.30-9.76) and low-albumin (OR 2.26, 95% CI 1.28-4.00) were associated with increased risk of 30-day postoperative complications. For infectious complications, steroid use (OR 3.67, 95% CI 1.57-8.57, P=0.003) and low hemoglobin (OR 3.03, 95% CI 1.32-6.96, P=0.009) were associated with increased risk in multivariate analysis. Propensity score matched analysis demonstrated that the risks of postoperative complications were not different among patients preoperatively receiving vedolizumab, anti-TNF-α agents or non-biological therapy (UC, P=0.40; CD, P=0.35). In the present study, preoperative vedolizumab exposure did not affect the risk of 30-day postoperative complications in UC and CD. Further, larger studies are required to confirm our findings.

Drug development for exceptionally rare metabolic diseases: challenging but not impossible.

PubMed

Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Wied, Christine C Gispen-de; Hoes, Arno W; Leufkens, Hubert G M; de Vrueh, Remco L A

2013-11-15

We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the 'Orphanet database of Rare diseases'. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest.

Physical Activity Level of Korean Adults with Chronic Diseases: The Korean National Health and Nutritional Examination Survey, 2010-2012.

PubMed

Jin, Ho-Seong; An, Ah-Reum; Choi, Ho-Chun; Lee, Sang-Hyun; Shin, Dong-Heon; Oh, Seung-Min; Seo, Young-Gyun; Cho, Be-Long

2015-11-01

Proper physical activities are known to be helpful in the prevention and management of chronic diseases. However, the physical activity level of patients with chronic diseases is low. Therefore, this study aimed to investigate the physical activity compliance of patients with hypertension, diabetes, and dyslipidemia in Korea. This study analyzed the 2010-2012 Fifth Korean National Health and Nutrition Examination Survey data. We included 13,873 individuals in the analysis. The level of physical activity compliance was measured by performing multivariate logistic regression analyses. In the univariate analysis, the subjects with hypertension or diabetes tended to comply with the physical activity guidelines less faithfully than their healthy counterparts. The proportion of subjects with hypertension who were insufficiently physically active was 65.4% among the men and 75.8% among the women. For diabetes, the proportions were 66.7% and 76.8%, respectively. No significant difference was found between the subjects with dyslipidemia and their healthy counterparts. In the multivariate logistic regression analysis, no significant difference in physical activity compliance was observed between the subjects with hypertension, diabetes, or dyslipidemia and their healthy counterparts for both sexes. The patients with hypertension or diabetes tended to have lower physical activity prevlaence than their healthy counterparts. However, for dyslipidemia, no significant difference was found between the two groups. Given the significance of physical activities in the management of chronic diseases, the physical activities of these patients need to be improved.

Analysis of cohort studies with multivariate and partially observed disease classification data.

PubMed

Chatterjee, Nilanjan; Sinha, Samiran; Diver, W Ryan; Feigelson, Heather Spencer

2010-09-01

Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.

Prevalence and factors associated with rheumatic diseases and chronic joint symptoms in the elderly.

PubMed

Falsarella, Gláucia R; Coimbra, Ibsen B; Barcelos, Caroline C; Costallat, Lilian Tl; Carvalho, Olga Mf; Coimbra, Arlete Mv

2013-10-01

In the elderly population, rheumatic conditions are major causes of pain that restrict participation in activities and mobility, and cause difficulties in the execution of self-care tasks. The present study aimed to analyze the prevalence and factors associated with the self-reported rheumatic diseases and chronic joint symptoms of the elderly. This transversal epidemiological survey involved 2209 older adults (aged ≥ 60 years). The investigation included sociodemographic factors, anthropometrics, activities of daily living, chronic conditions, medication and quality of life. Univariate and multivariate regression analysis were used for statistical procedures, P ≤ 0.05. The prevalence of rheumatism was 22.7%. Multivariate analysis showed that rheumatism was correlated with the following: female sex (OR = 1.91), high income (OR = 2.34), cardiovascular disease (OR = 1.42), cataracts (OR = 1.39), glucocorticoids (OR = 5.24), other anti-inflammatory medications (OR = 2.24) and pain (OR = 0.983). After adjusting for age and glucocorticoids, an association between cataracts and rheumatism was detected (OR = 1.32). The prevalence of symptoms was 45.6%. Multivariate regression results for symptoms included the following: female sex (OR = 1.40), body mass index ≥ 30.0 kg/m(2) (OR = 3.31), functional capacity (OR = 0.990), general health (OR = 0.993) and pain (OR = 0.981). After adjustment for age and glucocorticoids, an association between cataracts and symptoms was detected (OR = 1.26). There was a significant association of rheumatism and symptoms with women and high incomes. Obesity was associated with joint symptoms, which in turn were associated with an impaired quality of life. Cataracts and cardiovascular disease were associated with rheumatism. The identification of these characteristics in the elderly will contribute to a better understanding of this systemic disease and should be used to plan effective preventive measures. © 2013 Japan Geriatrics Society.

Association of educational status with cardiovascular disease: Teheran Lipid and Glucose Study.

PubMed

Hajsheikholeslami, Farhad; Hatami, Masumeh; Hadaegh, Farzad; Ghanbarian, Arash; Azizi, Fereidoun

2011-06-01

The aim of this study was to evaluate the associations between educational level and cardiovascular disease (CVD) in an older Iranian population. To estimate the odds ratio (OR) of educational level in a cross-sectional study, logistic regression analysis was used on 1,788 men and 2,204 women (222 men and 204 women positive based on their CVD status) aged ≥ 45 years. In men, educational levels of college degree and literacy level below diploma were inversely associated with CVD in the multivariate model [0.52 (0.28-0.94), 0.61 (0.40-0.92), respectively], but diploma level did not show any significant association with CVD, neither in the crude model nor in the multivariate model. In women, increase in educational level was inversely associated with risk of CVD in the crude model, but in the multivariate adjusted model, literacy level below diploma decreased risk of CVD by 39%, compared with illiteracy. Our findings support those of developed countries that, along with other CVD risk factors, educational status has an inverse association with CVD among a representative Iranian population of older men and women.

Elective Thoracolumbar Spine Fusion Surgery in Patients with Parkinson Disease.

PubMed

Puvanesarajah, Varun; Jain, Amit; Qureshi, Rabia; Carstensen, S Evan; Tyger, Rosemarie; Hassanzadeh, Hamid

2016-12-01

Few data are available concerning clinical outcomes in patients with Parkinson disease who undergo elective thoracolumbar spine fusion surgery. The goal of this study is to elucidate complication and revision rates after posterior thoracolumbar fusion surgery in patients with Parkinson disease, with a focus on how Parkinson disease modifies these rates. The PearlDiver database (2005-2012) was queried for patients who underwent posterior approach thoracolumbar fusion from 2006 to 2011. Cohorts of patients with a previous diagnosis of Parkinson disease (n = 4816) and without (n = 280,702) were compared. Multivariate analysis that included various comorbidities and demographics was used to calculate effects of Parkinson disease on development of postoperative infection and major medical complications within 90 days and revision surgery within 1 year. For analyses, significance was set at P < 0.001. Major medical complications were observed in 545 patients (11.3%) for 90 days after the index procedure. Postoperative infection was noted in 91 patients (1.9%) within 90 days, and revision surgeries were performed in 250 patients (5.2%) within 1 year. Multivariate analysis showed that Parkinson disease was significantly associated with an increased risk for medical complications (adjusted odds ratio, 1.22; 95% confidence interval, 1.11-1.34; P < 0.001) and revision surgery (adjusted odds ratio, 1.70; 95% confidence interval, 1.49-1.93; P < 0.001), but not postoperative infection (P = 0.02). Patients with Parkinson disease are more likely to require revision surgery and have higher rates of adverse medical events postoperatively. Patients with Parkinson disease should be appropriately selected to ensure favorable clinical outcomes. Copyright © 2016. Published by Elsevier Inc.

Diagnostic Significance of Cortical Superficial Siderosis for Alzheimer Disease in Patients with Cognitive Impairment.

PubMed

Inoue, Y; Nakajima, M; Uetani, H; Hirai, T; Ueda, M; Kitajima, M; Utsunomiya, D; Watanabe, M; Hashimoto, M; Ikeda, M; Yamashita, Y; Ando, Y

2016-02-01

Because the diagnostic significance of cortical superficial siderosis for Alzheimer disease and the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds have been unclear, we investigated the association between cortical superficial siderosis and clinicoradiologic characteristics of patients with cognitive impairment. We studied 347 patients (217 women, 130 men; mean age, 74 ± 9 years) who visited our memory clinic and underwent MR imaging (3T SWI). We analyzed the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds plus clinical characteristics including types of dementia. We used multivariate logistic regression analysis to determine the diagnostic significance of cortical superficial siderosis for Alzheimer disease. Twelve patients (3.5%) manifested cortical superficial siderosis. They were older (P = .026) and had strictly lobar cerebral microbleeds significantly more often than did patients without cortical superficial siderosis (50.0% versus 19.4%, P = .02); the occurrence of strictly deep and mixed cerebral microbleeds, however, did not differ in the 2 groups. Alzheimer disease was diagnosed in 162 (46.7%) patients. Of these, 8 patients (4.9%) had cortical superficial siderosis. In the multivariate logistic regression analysis for the diagnosis of Alzheimer disease, lacunar infarcts were negatively and independently associated with Alzheimer disease (P = .007). Although cortical superficial siderosis was associated with a strictly lobar cerebral microbleed location, it was not independently associated with Alzheimer disease in a memory clinic setting. Additional studies are required to investigate the temporal changes of these cerebral amyloid angiopathy-related MR imaging findings. © 2016 by American Journal of Neuroradiology.

Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn's Disease and Ulcerative Colitis.

PubMed

Bruno, Maria E C; Rogier, Eric W; Arsenescu, Razvan I; Flomenhoft, Deborah R; Kurkjian, Cathryn J; Ellis, Gavin I; Kaetzel, Charlotte S

2015-10-01

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation due to immunological, microbial, and environmental factors in genetically predisposed individuals. Advances in the diagnosis, prognosis, and treatment of IBD require the identification of robust biomarkers that can be used for molecular classification of diverse disease presentations. We previously identified five genes, RELA, TNFAIP3 (A20), PIGR, TNF, and IL8, whose mRNA levels in colonic mucosal biopsies could be used in a multivariate analysis to classify patients with CD based on disease behavior and responses to therapy. We compared expression of these five biomarkers in IBD patients classified as having CD or UC, and in healthy controls. Patients with CD were characterized as having decreased median expression of TNFAIP3, PIGR, and TNF in non-inflamed colonic mucosa as compared to healthy controls. By contrast, UC patients exhibited decreased expression of PIGR and elevated expression of IL8 in colonic mucosa compared to healthy controls. A multivariate analysis combining mRNA levels for all five genes resulted in segregation of individuals based on disease presentation (CD vs. UC) as well as severity, i.e., patients in remission versus those with acute colitis at the time of biopsy. We propose that this approach could be used as a model for molecular classification of IBD patients, which could further be enhanced by the inclusion of additional genes that are identified by functional studies, global gene expression analyses, and genome-wide association studies.

Multivariate pattern recognition for diagnosis and prognosis in clinical neuroimaging: state of the art, current challenges and future trends.

PubMed

Haller, Sven; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon; Van De Ville, Dimitri

2014-05-01

Many diseases are associated with systematic modifications in brain morphometry and function. These alterations may be subtle, in particular at early stages of the disease progress, and thus not evident by visual inspection alone. Group-level statistical comparisons have dominated neuroimaging studies for many years, proving fascinating insight into brain regions involved in various diseases. However, such group-level results do not warrant diagnostic value for individual patients. Recently, pattern recognition approaches have led to a fundamental shift in paradigm, bringing multivariate analysis and predictive results, notably for the early diagnosis of individual patients. We review the state-of-the-art fundamentals of pattern recognition including feature selection, cross-validation and classification techniques, as well as limitations including inter-individual variation in normal brain anatomy and neurocognitive reserve. We conclude with the discussion of future trends including multi-modal pattern recognition, multi-center approaches with data-sharing and cloud-computing.

Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis.

PubMed

Xing, Yan; Chang, George J; Hu, Chung-Yuan; Askew, Robert L; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2010-05-01

Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision making. Patients with melanoma and at least 5 years of follow-up were identified from the Surveillance Epidemiology and End Results registry (1988-2000). By using the methods of Kaplan and Meier, stage-specific, 5-year CS estimates were independently calculated for survivors for each year after diagnosis. Stage-specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma-specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology. Five-year CS estimates for patients with stage I disease remained constant at 97% annually, while for patients with stages II, III, and IV disease, 5-year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender, and race decreased over time. Five-year melanoma-specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and nontreatment related life decisions. (c) 2010 American Cancer Society.

Risk factors for hospital readmission of elderly patients.

PubMed

Franchi, Carlotta; Nobili, Alessandro; Mari, Daniela; Tettamanti, Mauro; Djade, Codjo D; Pasina, Luca; Salerno, Francesco; Corrao, Salvatore; Marengoni, Alessandra; Iorio, Alfonso; Marcucci, Maura; Mannucci, Pier Mannuccio

2013-01-01

The aim of this study was to identify which factors were associated with a risk of hospital readmission within 3 months after discharge of a sample of elderly patients admitted to internal medicine and geriatric wards. Of the 1178 patients aged 65 years or more and discharged from one of the 66 wards of the 'Registry Politerapie SIMI (REPOSI)' during 2010, 766 were followed up by phone interview 3 months after discharge and were included in this analysis. Univariate and multivariate logistic regression models were used to evaluate the association of several variables with rehospitalization within 3 months from discharge. Nineteen percent of patients were readmitted at least once within 3 months after discharge. By univariate analysis in-hospital clinical adverse events (AEs), a previous hospital admission, number of diagnoses and drugs, comorbidity and severity index (according to Cumulative Illness Rating Scale-CIRS), vascular and liver diseases with a level of impairment at discharge of 3 or more at CIRS were significantly associated with risk of readmission. Multivariate logistic regression analysis showed that only AEs during hospitalization, previous hospital admission, and vascular and liver diseases were significantly associated with the likelihood of readmission. The results demonstrate the need for increased medical attention towards elderly patients discharged from hospital with characteristics such as AEs during the hospitalization, previous admission, vascular and liver diseases. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

Cardiovascular risk in peritoneal dialysis - a Portuguese multicenter study.

PubMed

Neves, Marta; Machado, Susana; Rodrigues, Luís; Borges, Andreia; Maia, Pedro; Campos, Mário

2014-01-01

Cardiovascular (CV) disease is the major cause of mortality in patients undergoing renal replacement therapy. The primary aim of the study was to evaluate the CV risk profile and prevalence of CV disease in patients on peritoneal dialysis (PD) in Portugal. The secondary goal was to establish parameters most associated with CV disease. Retrospective, multicenter study of the prevalent adult population on PD. Six hundred patients were included (56.7% male; mean age 53.5 ± 15.3 years), on PD for 25.6 ± 21.9 months. Patients were divided into two groups: group 1 (n=166) with CV disease and group 2 (n=434) without CV disease. Comparisons were made regarding traditional CV risk factors and those associated with uremia and PD itself, and a multivariate analysis was performed to determine variables independently associated with CV disease. At the end of the study, the prevalence of CV disease was 28%. At univariate analysis, group 1 presented a higher frequency of males (p<.01), older patients (p<.01), diabetics (p<.01), occurrence of left ventricular hypertrophy (LVH) (p<.01), mean C-reactive protein (CRP) (p=.04), lower mean parathormone level (p=.014), lower serum phosphorus (p=.02), lower daily urine output (p=.04), lower weekly Kt/V (p=.008), increased use of icodextrin and hypertonic glucose-based PD solutions (p<.001 and p=.006, respectively) and more were under continuous ambulatory PD (CAPD) (p=.014) and had a high peritoneal transport status (p=.02). Multivariate analysis provided a significant discriminatory influence pertaining to age >50 years, CRP>0.6 mg/dl, male gender, diabetes, LVH, CAPD and anuria, when comparing group 1 and group 2. Risk factors most related to the development of CV disease in PD in Portugal are age >50 years, CRP>0.6 mg/dL, male gender, diabetes, LVH, CAPD and anuria.

Comparison of chest CT findings in nontuberculous mycobacterial diseases vs. Mycobacterium tuberculosis lung disease in HIV-negative patients with cavities.

PubMed

Kim, Cherry; Park, So Hee; Oh, Sang Young; Kim, Sung-Soo; Jo, Kyung-Wook; Shim, Tae Sun; Kim, Mi Young

2017-01-01

This article focuses on the differences between CT findings of HIV-negative patients who have cavities with nontuberculous mycobacteria (NTM) disease and those with Mycobacterium tuberculosis infections (TB). We retrospectively reviewed 128 NTM disease patients (79 males and 49 females) with cavities in chest CT, matched for age and gender with 128 TB patients in the same period. Sputum cultures of all patients were positive for pathogens. Two independent chest radiologists evaluated the characteristics of the largest cavity and related factors. Interobserver agreement was excellent (κ value, 0.853-0.938). Cavity walls in NTM disease were significantly thinner (6.9±4 mm vs 10.9±6 mm, P<0.001) and more even (the ratio of thickness, 2.6±1 vs 3.7±2, P<0.001) than those in TB. The thickening of adjacent pleura next to the cavity was also significantly thicker in NTM than TB (P<0.001). However, in the multivariate analysis, thickening of adjacent pleura was the only significant factor among the representative cavity findings (Odds ratio [OR], 6.49; P<0.001). In addition, ill-defined tree-in-bud nodules (OR, 8.82; P<0.001), number of non-cavitary nodules (≥10mm) (OR, 0.72; P = 0.003), and bronchiectasis in the RUL (OR, 5.3; P = 0.002) were significantly associated ancillary findings with NTM disease in the multivariate analysis. The major cavities in NTM disease generally have thinner and more even walls than those in TB. When cavities are associated with adjacent pleural thickening, ill-defined satellite tree-in-bud nodules, or fewer non-cavitary nodules ≥10 mm, these CT findings are highly suggestive of NTM disease rather than TB.

Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence.

PubMed

Alvarez-Lobos, Manuel; Arostegui, Juan I; Sans, Miquel; Tassies, Dolors; Plaza, Susana; Delgado, Salvadora; Lacy, Antonio M; Pique, Josep M; Yagüe, Jordi; Panés, Julián

2005-11-01

To study the predictive value of Nod2/CARD15 gene variants along with disease phenotypic characteristics for requirement of initial surgery and for surgical recurrence in Crohn's disease (CD). Nod2/CARD15 gene variants play an important role in the susceptibility to CD. Studies of genotype-phenotype relationship suggest that these variants are associated with development of intestinal strictures. Preliminary reports analyzing the association between these variants and need for surgery have produced inconsistent results. A total of 170 CD patients were included prospectively in the study and followed up regularly for a mean of 7.4 +/- 6.1 years. Clinical characteristics of CD, time and indication for surgery, and recurrence were registered. Nod2/CARD15 gene variants were determined by DNA sequencing analysis. Surgery for stricturing disease was significantly more frequent in patients with Nod2/CARD15 variants in the univariate analysis (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.42-9.27), and it was required at an earlier time (P = 0.004). Only Nod2/CARD15 variants (OR, 3.58; 95% CI, 1.21-10.5) and stricturing phenotype at diagnosis of CD (OR, 9.34; 95% CI, 2.56-33.3) were independent predictive factors of initial surgery for stricturing lesions in the multivariate analysis. Among 70 patients that required surgery, postoperative recurrence was also more frequent in patients with Nod2/CARD15 variants in the univariate and multivariate analysis (OR, 3.29; 95% CI, 1.13-9.56), and reoperation was needed at an earlier time (P = 0.03). Nod2/CARD15 variants are associated with early initial surgery due to stenosis and with surgical recurrence in Crohn's disease. Patients with these variants could benefit from preventive and/or early therapeutic strategies.

Risk of chronic and end stage kidney disease in patients with nephrolithiasis.

PubMed

Shoag, Jonathan; Halpern, Joshua; Goldfarb, David S; Eisner, Brian H

2014-11-01

We examine kidney stone disease as a potential risk factor for chronic kidney disease, end stage kidney disease and treatment with dialysis. The NHANES (National Health and Nutrition Examination Survey) 2007-2010 database was interrogated for patients with a history of kidney stones. Demographics and comorbid conditions including age, gender, body mass index, diabetes, hemoglobin A1c, hypertension, gout and smoking were also assessed. Multivariate analysis adjusting for patient demographics and comorbidities was performed to assess differences in the prevalence of chronic kidney disease and treatment with dialysis between the 2 groups. History of nephrolithiasis was assessed with the question, "Have you ever had kidney stones?" Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) and/or a urinary albumin-to-creatinine ratio greater than 30 mg/gm. Statistical calculations were performed using Stata® software with determinations of p values and 95% CI where appropriate. The study included an analysis of 5,971 NHANES participants for whom data on chronic kidney disease and kidney stones were available, of whom 521 reported a history of kidney stones. On multivariate analysis a history of kidney stones was associated with chronic kidney disease and treatment with dialysis (OR 1.50, 1.10-2.04, p = 0.013 and OR 2.37, 1.13-4.96, p = 0.025, respectively). This difference appeared to be driven by women, where a history of kidney stones was associated with a higher prevalence of chronic kidney disease (OR 1.76, 1.13-2.763, p = 0.016) and treatment with dialysis (OR 3.26, 1.48-7.16, p = 0.004). There was not a significant association between kidney stone history and chronic kidney disease or treatment with dialysis in men. Kidney stone history is associated with an increased risk of chronic kidney disease and treatment with dialysis among women even after adjusting for comorbid conditions. Large scale prospective studies are needed to further characterize the relationship between nephrolithiasis and chronic kidney disease. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Detection and characterization of glaucoma-like canine retinal tissues using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Qi; Grozdanic, Sinisa D.; Harper, Matthew M.; Hamouche, Karl; Hamouche, Nicholas; Kecova, Helga; Lazic, Tatjana; Hernandez-Merino, Elena; Yu, Chenxu

2013-06-01

Early detection of pathological changes and progression in glaucoma and other neuroretinal diseases remains a great challenge and is critical to reduce permanent structural and functional retina and optic nerve damage. Raman spectroscopy is a sensitive technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, spectroscopic analysis was conducted on the retinal tissues of seven beagles with acute elevation of intraocular pressure (AEIOP), six beagles with compressive optic neuropathy (CON), and five healthy beagles. Spectroscopic markers were identified associated with the different neuropathic conditions. Furthermore, the Raman spectra were subjected to multivariate discriminate analysis to classify independent tissue samples into diseased/healthy categories. The multivariate discriminant model yielded an average optimal classification accuracy of 72.6% for AEIOP and 63.4% for CON with 20 principal components being used that accounted for 87% of the total variance in the data set. A strong correlation (R2>0.92) was observed between pattern electroretinography characteristics of AEIOP dogs and Raman separation distance that measures the separation of spectra of diseased tissues from normal tissues; however, the underlining mechanism of this correlation remains to be understood. Since AEIOP mimics the pathological symptoms of acute/early-stage glaucoma, it was demonstrated that Raman spectroscopic screening has the potential to become a powerful tool for the detection and characterization of early-stage disease.

Magnetic resonance imaging and magnetic resonance spectroscopy for detection of early Alzheimer's disease.

PubMed

Westman, Eric; Wahlund, Lars-Olof; Foy, Catherine; Poppe, Michaela; Cooper, Allison; Murphy, Declan; Spenger, Christian; Lovestone, Simon; Simmons, Andrew

2011-01-01

Alzheimer's disease is the most common form of neurodegenerative disorder and early detection is of great importance if new therapies are to be effectively administered. We have investigated whether the discrimination between early Alzheimer's disease (AD) and elderly healthy control subjects can be improved by adding magnetic resonance spectroscopy (MRS) measures to magnetic resonance imaging (MRI) measures. In this study 30 AD patients and 36 control subjects were included. High resolution T1-weighted axial magnetic resonance images were obtained from each subject. Automated regional volume segmentation and cortical thickness measures were determined for the images. 1H MRS was acquired from the hippocampus and LCModel was used for metabolic quantification. Altogether, this yielded 58 different volumetric, cortical thickness and metabolite ratio variables which were used for multivariate analysis to distinguish between subjects with AD and Healthy controls. Combining MRI and MRS measures resulted in a sensitivity of 97% and a specificity of 94% compared to using MRI or MRS measures alone (sensitivity: 87%, 76%, specificity: 86%, 83% respectively). Adding the MRS measures to the MRI measures more than doubled the positive likelihood ratio from 6 to 17. Adding MRS measures to a multivariate analysis of MRI measures resulted in significantly better classification than using MRI measures alone. The method shows strong potential for discriminating between Alzheimer's disease and controls.

A multivariate test of disease risk reveals conditions leading to disease amplification.

PubMed

Halliday, Fletcher W; Heckman, Robert W; Wilfahrt, Peter A; Mitchell, Charles E

2017-10-25

Theory predicts that increasing biodiversity will dilute the risk of infectious diseases under certain conditions and will amplify disease risk under others. Yet, few empirical studies demonstrate amplification. This contrast may occur because few studies have considered the multivariate nature of disease risk, which includes richness and abundance of parasites with different transmission modes. By combining a multivariate statistical model developed for biodiversity-ecosystem-multifunctionality with an extensive field manipulation of host (plant) richness, composition and resource supply to hosts, we reveal that (i) host richness alone could not explain most changes in disease risk, and (ii) shifting host composition allowed disease amplification, depending on parasite transmission mode. Specifically, as predicted from theory, the effect of host diversity on parasite abundance differed for microbes (more density-dependent transmission) and insects (more frequency-dependent transmission). Host diversity did not influence microbial parasite abundance, but nearly doubled insect parasite abundance, and this amplification effect was attributable to variation in host composition. Parasite richness was reduced by resource addition, but only in species-rich host communities. Overall, this study demonstrates that multiple drivers, related to both host community and parasite characteristics, can influence disease risk. Furthermore, it provides a framework for evaluating multivariate disease risk in other systems. © 2017 The Author(s).

The association between glucose levels and hospital outcomes in patients with acute exacerbations of chronic obstructive pulmonary disease

PubMed Central

Islam, Ebtesam A.; Limsuwat, Chok; Nantsupawat, Teerapat; Berdine, Gilbert G.; Nugent, Kenneth M.

2015-01-01

BACKGROUND: Corticosteroids used for chronic obstructive pulmonary disease (COPD) exacerbations can cause hyperglycemia in hospitalized patients, and hyperglycemia may be associated with increased mortality, length of stay (LOS), and re-admissions in these patients. MATERIALS AND METHODS: We did three retrospective studies using charts from July 2008 through June 2009, January 2006 through December 2010, and October 2010 through March 2011. We collected demographic and clinical information, laboratory results, radiographic results, and information on LOS, mortality, and re-admission. RESULTS: Glucose levels did not predict outcomes in any of the studied cohorts, after adjustment for covariates in multivariable analysis. The first database included 30 patients admitted to non-intensive care unit (ICU) hospital beds. Six of 20 non-diabetic patients had peak glucoses above 200 mg/dl. Nine of the ten diabetic patients had peak glucoses above 200 mg/dl. The maximum daily corticosteroid dose had no apparent effect on the glucose levels. The second database included 217 patients admitted to ICUs. The initial blood glucose was higher in patients who died than those who survived using bivariate analysis (P = 0.015; odds ratio, OR, 1.01) but not in multivariable analysis. Multivariable logistic regression analysis also demonstrated that glucose levels did not affect LOS. The third database analyzing COPD re-admission rates included 81 patients; the peak glucose levels were not associated with re-admission. CONCLUSIONS: Our data demonstrate that COPD patients treated with corticosteroids developed significant hyperglycemia, but the increase in blood glucose levels did not correlate with the maximum dose of corticosteroids. Blood glucose levels were not associated with mortality, LOS, or re-admission rates. PMID:25829959

Targeted metabolomic profiling in rat tissues reveals sex differences.

PubMed

Ruoppolo, Margherita; Caterino, Marianna; Albano, Lucia; Pecce, Rita; Di Girolamo, Maria Grazia; Crisci, Daniela; Costanzo, Michele; Milella, Luigi; Franconi, Flavia; Campesi, Ilaria

2018-03-16

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions.

CXCL13 and CCL11 Serum Levels and Lymphoma and Disease Activity in Primary Sjögren's Syndrome.

PubMed

Nocturne, G; Seror, R; Fogel, O; Belkhir, R; Boudaoud, S; Saraux, A; Larroche, C; Le Guern, V; Gottenberg, J E; Mariette, X

2015-12-01

Non-Hodgkin's lymphoma (NHL) is a severe complication of primary Sjögren's syndrome (SS). Ectopic germinal centers (GCs) in the salivary glands are predictors of the occurrence of NHL. Given the association between CCL11 and CXCL13 and ectopic GCs, we assessed the link between these chemokines and NHL, as well as the association between these chemokines and disease activity, in patients with primary SS. Serum levels of CCL11 and CXCL13 were evaluated by multiplex assay in 385 patients included in the Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. The association between chemokine levels, B cell biomarkers, and patient subsets was assessed using Spearman's test for continuous data and the nonparametric Mann-Whitney U test for categorical data. Multivariate analyses were performed to identify parameters associated with lymphoma and disease activity. Seventeen patients had a history of lymphoma, and 5 of them had developed NHL during followup. The median serum levels of CCL11 and CXCL13 in the total cohort were 106.48 pg/ml (interquartile range 69.33-149.85) and 108.31 pg/ml (interquartile range 58.88-200.13), respectively. Patients with lymphoma had higher levels of CXCL13 than did patients without lymphoma (P = 0.006) and a trend toward a higher level of CCL11 (P = 0.056). Low C4 and high BAFF levels were associated with NHL on multivariate analysis (P = 0.01 and P = 0.0002, respectively). CCL11 and CXCL13 levels correlated positively with the rheumatoid factor titer, the κ-to-λ free light chain ratio, and the β2 -microglubulin level. CXCL13 was the only parameter associated with disease activity on multivariate analysis. These findings demonstrate a link between CXCL13 and CCL11 and disease activity and lymphoma. This highlights the continuum between chronic B cell activation, disease activity, and lymphomagenesis in patients with primary SS. © 2015, American College of Rheumatology.

Breath Analysis in Disease Diagnosis: Methodological Considerations and Applications

PubMed Central

Lourenço, Célia; Turner, Claire

2014-01-01

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles. PMID:24957037

Breath analysis in disease diagnosis: methodological considerations and applications.

PubMed

Lourenço, Célia; Turner, Claire

2014-06-20

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. "Breath fingerprinting", indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles.

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

PubMed Central

2009-01-01

Background To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. Methods We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Results Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Conclusion Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients. PMID:19723317

Current clinical presentation and treatment of localized prostate cancer in the United States.

PubMed

Mahmood, Usama; Levy, Lawrence B; Nguyen, Paul L; Lee, Andrew K; Kuban, Deborah A; Hoffman, Karen E

2014-12-01

SEER recently released patient Gleason scores at biopsy/transurethral resection of the prostate. For the first time this permits accurate assessment of prostate cancer presentation and treatment according to clinical factors at diagnosis. We used the SEER database to identify men diagnosed with localized prostate cancer in 2010 who were assigned NCCN(®) risk based on clinical factors. We identified sociodemographic factors associated with high risk disease and analyzed the impact of these factors along with NCCN risk on local treatment. Of the 42,403 men identified disease was high, intermediate and low risk in 38%, 40% and 22%, respectively. On multivariate analysis patients who were older, nonwhite, unmarried or living in a county with a higher poverty rate were more likely to be diagnosed with high risk disease (each p <0.05). Of the 38,634 men in whom prostate cancer was the first malignancy 23% underwent no local treatment, 40% were treated with prostatectomy, 36% received radiation therapy and 1% underwent local tumor destruction, predominantly cryotherapy. On multivariate analysis patients who were older, black, unmarried or living in a county with a higher poverty rate, or who had low risk disease were less likely to receive local treatment (each p <0.05). Our analysis provides information on the current clinical presentation and treatment of localized prostate cancer in the United States. Nonwhite and older men living in a county with a higher poverty rate were more likely to be diagnosed with high risk disease and less likely to receive local treatment. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

p53 predictive value for pT1-2 N0 disease at radical cystectomy.

PubMed

Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

2009-09-01

Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

PubMed

Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

2017-10-03

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

Hierarchical multivariate covariance analysis of metabolic connectivity.

PubMed

Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J

2014-12-01

Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Multivariate analysis of stripe rust assessment and reactions of barley in multi-location nurseries

USDA-ARS?s Scientific Manuscript database

A total of 1357 entries, mainly consisting of hulled two-row, hulled six-row and hulless barley, were evaluated in stripe rust nurseries at Toluca, Mexico during 2007, Quito, Ecuador during 2007 and 2008, and Pullman and Mt. Vernon, USA [Pacific Northwest (PNW)] during 2007_2009. Disease screening d...

Sequence of Radiotherapy and Chemotherapy in Breast Cancer After Breast-Conserving Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jobsen, Jan J., E-mail: J.Jobsen@mst.nl; Palen, Job van der; Department of Research Methodology, Measurement and Data Analysis, Faculty of Behavioural Science, University of Twente

2012-04-01

Purpose: The optimal sequence of radiotherapy and chemotherapy in breast-conserving therapy is unknown. Methods and Materials: From 1983 through 2007, a total of 641 patients with 653 instances of breast-conserving therapy (BCT), received both chemotherapy and radiotherapy and are the basis of this analysis. Patients were divided into three groups. Groups A and B comprised patients treated before 2005, Group A radiotherapy first and Group B chemotherapy first. Group C consisted of patients treated from 2005 onward, when we had a fixed sequence of radiotherapy first, followed by chemotherapy. Results: Local control did not show any differences among the threemore » groups. For distant metastasis, no difference was shown between Groups A and B. Group C, when compared with Group A, showed, on univariate and multivariate analyses, a significantly better distant metastasis-free survival. The same was noted for disease-free survival. With respect to disease-specific survival, no differences were shown on multivariate analysis among the three groups. Conclusion: Radiotherapy, as an integral part of the primary treatment of BCT, should be administered first, followed by adjuvant chemotherapy.« less

Prognostic Significance of Solid and Micropapillary Components in Invasive Lung Adenocarcinomas Measuring ≤3 cm.

PubMed

Matsuoka, Yuki; Yurugi, Yohei; Takagi, Yuzo; Wakahara, Makoto; Kubouchi, Yasuaki; Sakabe, Tomohiko; Haruki, Tomohiro; Araki, Kunio; Taniguchi, Yuji; Nakamura, Hiroshige; Umekita, Yoshihisa

2016-09-01

We aimed to analyze the clinical impact of solid and micropapillary components in a series of Japanese patients resected for ≤3 cm lung adenocarcinoma. A total of 115 patients with ≤3 cm lung adenocarcinomas were reviewed and classified according to the American Thoracic Society and the European Respiratory Society classification. The presence of solid (S+) or micropapillary component (MP+) was defined when the component constituted ≥1% of the entire tumor. The impact of these components on disease-free (DFS) and disease-specific (DSS) survival was analyzed. Thirty (26.1%) cases with S+ and 27 (23.5%) with MP+ were identified, and multivariate analysis indicated that S+ status significantly reduced the duration of DFS and DSS. In 86 patients of acinar- and papillary-predominant subgroups, S+ and/or MP+ had the most significant effect on DFS and DSS by multivariate analysis. S+ and/or MP+ status predict worse prognosis in patients with acinar- and papillary-predominant lung adenocarcinoma. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Ovarian Conservation and Overall Survival in Young Women With Early-Stage Cervical Cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D

2017-01-01

To identify predictors of ovarian conservation at hysterectomy and to examine the association of ovarian conservation and survival of young women with early-stage cervical cancer. This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program to identify hysterectomy-based surgically treated patients with stage I cervical cancer diagnosed between 1983 and 2012 (N=16,511). Multivariable models were used to identify independent factors associated with ovarian conservation. Among the subgroup of 9,419 women younger than 50 years of age with stage I disease, survival outcomes and causes of death were examined for 3,908 (41.5%) women who underwent ovarian conservation at hysterectomy without radiotherapy. On multivariable analysis, age younger than 50 years, stage IA disease, and squamous histology were independent factors associated with ovarian conservation (all, P<.001). Among 5,526 women younger than 50 years of age with stage IA disease who underwent hysterectomy without radiotherapy, overall survival was significantly higher in patients undergoing ovarian conservation than in those undergoing oophorectomy (20-year rate, 93.5% compared with 86.8%, P<.001); cervical cancer-specific survival was similar between the patients who underwent ovarian conservation and those who underwent oophorectomy (98.8% compared with 97.8%, P=.12). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.63, 95% confidence interval [CI] 0.49-0.82, P=.001) and was independently associated with lower cumulative risks of death resulting from cardiovascular disease (20-year cumulative rate, 1.2% compared with 3.3%, adjusted hazard ratio 0.47, 95% CI 0.26-0.86, P=.014) and other chronic disease (0.5% compared with 1.4%, adjusted hazard ratio 0.24, 95% CI 0.09-0.65, P=.005) compared with oophorectomy. Both cervical cancer-specific survival (20-year rate, 93.1% compared with 92.0%, P=.37) and overall survival (86.7% compared with 84.6%, P=.12) were similar between ovarian conservation and oophorectomy among 3,893 women younger than 50 years of age with stage IB disease who underwent hysterectomy without radiotherapy. Among young women with stage IA cervical cancer, ovarian conservation at hysterectomy is associated with decreased all-cause mortality including death resulting from cardiovascular disease and other chronic diseases.

A FORTRAN program for multivariate survival analysis on the personal computer.

PubMed

Mulder, P G

1988-01-01

In this paper a FORTRAN program is presented for multivariate survival or life table regression analysis in a competing risks' situation. The relevant failure rate (for example, a particular disease or mortality rate) is modelled as a log-linear function of a vector of (possibly time-dependent) explanatory variables. The explanatory variables may also include the variable time itself, which is useful for parameterizing piecewise exponential time-to-failure distributions in a Gompertz-like or Weibull-like way as a more efficient alternative to Cox's proportional hazards model. Maximum likelihood estimates of the coefficients of the log-linear relationship are obtained from the iterative Newton-Raphson method. The program runs on a personal computer under DOS; running time is quite acceptable, even for large samples.

Application of reflectance spectroscopies (FTIR-ATR & FT-NIR) coupled with multivariate methods for robust in vivo detection of begomovirus infection in papaya leaves

NASA Astrophysics Data System (ADS)

Haq, Quazi M. I.; Mabood, Fazal; Naureen, Zakira; Al-Harrasi, Ahmed; Gilani, Sayed A.; Hussain, Javid; Jabeen, Farah; Khan, Ajmal; Al-Sabari, Ruqaya S. M.; Al-khanbashi, Fatema H. S.; Al-Fahdi, Amira A. M.; Al-Zaabi, Ahoud K. A.; Al-Shuraiqi, Fatma A. M.; Al-Bahaisi, Iman M.

2018-06-01

Nucleic acid & serology based methods have revolutionized plant disease detection, however, they are not very reliable at asymptomatic stage, especially in case of pathogen with systemic infection, in addition, they need at least 1-2 days for sample harvesting, processing, and analysis. In this study, two reflectance spectroscopies i.e. Near Infrared reflectance spectroscopy (NIR) and Fourier-Transform-Infrared spectroscopy with Attenuated Total Reflection (FT-IR, ATR) coupled with multivariate exploratory methods like Principle Component Analysis (PCA) and Partial least square discriminant analysis (PLS-DA) have been deployed to detect begomovirus infection in papaya leaves. The application of those techniques demonstrates that they are very useful for robust in vivo detection of plant begomovirus infection. These methods are simple, sensitive, reproducible, precise, and do not require any lengthy samples preparation procedures.

Barriers to preemptive renal transplantation: a single center questionnaire study.

PubMed

Knight, Richard J; Teeter, Larry D; Graviss, Edward A; Patel, Samir J; DeVos, Jennifer M; Moore, Linda W; Gaber, A Osama

2015-03-01

Preemptive transplantation results in excellent patient and graft survival yet most transplant candidates are referred for transplantation after initiation of dialysis. The goal of this study was to determine barriers to preemptive renal transplantation. A nonvalidated questionnaire was administered to prospective kidney transplant recipients to determine factors that hindered or favored referral for transplantation before the initiation of dialysis. One hundred ninety-seven subjects referred for a primary renal transplant completed the questionnaire. Ninety-one subjects (46%) had been informed of preemptive transplantation before referral, and 80 (41%) were predialysis at the time of evaluation. The median time from diagnosis of renal disease to referral was 60 months (range, 2-444 months). In bivariate analysis, among other factors, knowledge of preemptive transplantation was highly associated (odds ratio=94.69) with referral before initiation of dialysis. Given the strong association between knowledge of preemptive transplantation and predialysis referral, this variable was not included in the multivariate analysis. Using multivariate logistic regression analysis, white recipient race, referral by a transplant nephrologist, recipient employment, and the diagnosis of polycystic kidney disease were significantly associated with presentation to the pretransplant clinic before initiation of dialysis. The principle barrier to renal transplantation referral before dialysis was patient education regarding the option of preemptive transplantation. Factors significantly associated with referral before dialysis were the diagnosis of polycystic kidney disease, white recipient race, referral by a transplant nephrologist, and employed status. Greater effort should be applied to patient education regarding preemptive transplantation early after the diagnosis of end-stage renal disease.

Chest wall recurrence after mastectomy does not always portend a dismal outcome.

PubMed

Chagpar, Anees; Meric-Bernstam, Funda; Hunt, Kelly K; Ross, Merrick I; Cristofanilli, Massimo; Singletary, S Eva; Buchholz, Thomas A; Ames, Frederick C; Marcy, Sylvie; Babiera, Gildy V; Feig, Barry W; Hortobagyi, Gabriel N; Kuerer, Henry M

2003-07-01

Chest wall recurrence (CWR) after mastectomy often forecasts a grim prognosis. Predictors of outcome after CWR, however, are not clear. From 1988 to 1998, 130 patients with isolated CWRs were seen at our center. Clinicopathologic factors were studied by univariate and multivariate analyses for distant metastasis-free survival after CWR. The median post-CWR follow-up was 37 months. Initial nodal status was the strongest predictor of outcome by univariate analysis. Other significant factors included initial T4 disease, primary lymphovascular invasion, treatment of the primary tumor with neoadjuvant therapy or radiation, time to CWR >24 months, and treatment for CWR (surgery, radiation, or multimodality therapy). Multivariate analysis also found initial nodal status to have the greatest effect; time to CWR and use of radiation for CWR were also independent predictors. Three groups of patients were identified. Low risk was defined by initial node-negative disease, time to CWR >24 months, and radiation for CWR; intermediate risk had one or two favorable features; and high risk had none. The median distant metastasis-free survival after CWR was significantly different among these groups (P <.0001). Patients with CWR are a heterogeneous population. Patients with initial node-negative disease who develop CWR after 24 months have an optimistic prognosis, especially if they are treated with radiation.

Early complications after pneumonectomy: retrospective study of 168 patients.

PubMed

Alloubi, Ihsan; Jougon, Jacques; Delcambre, Frédéric; Baste, Jean Marc; Velly, Jean François

2010-08-01

The purpose of this study was to assess the mortality and risk factors of complications after pneumonectomy for lung cancer. Between 1996 and 2001, we reviewed and analysed the demographic, clinical, functional, and surgical variables of 168 patients to identify risk factors of postoperative complications by univariate and multivariate analyses with Medlog software system. The mean age was 60+/-10 years, overall mortality and morbidity rates were 4.17% and 41.6%, respectively. All frequencies of respiratory complications were 1.2% for acute respiratory failure, 10.1% for pneumonia, 2.4% for acute pulmonary oedema, 4.17% for bronchopleural fistula, 2.4% for thoracic empyema and 18.5% for left recurrent nerve injuries. Postoperative arrhythmias developed in 46% of our patients. The risk factors for cardiopulmonary morbidity and mortality with univariate analysis were advanced age (P<0.01), preoperative poor performance status (P<0.015), and chronic artery disease (P<0.008). Factors adversely affecting morbidity with multivariate analysis included age (P=0.0001), associated cardiovascular disease (P=0.001), and altered forced expiratory volume in 1 s (P=0.0005). Complications after pneumonectomy are associated with high mortality. Careful attention must be paid to patients with advanced age and heart disease. Chest physiotherapy is paramount to have uneventful outcomes.

Predictive Utility of Marketed Volumetric Software Tools in Subjects at Risk for Alzheimer Disease: Do Regions Outside the Hippocampus Matter?

PubMed

Tanpitukpongse, T P; Mazurowski, M A; Ikhena, J; Petrella, J R

2017-03-01

Alzheimer disease is a prevalent neurodegenerative disease. Computer assessment of brain atrophy patterns can help predict conversion to Alzheimer disease. Our aim was to assess the prognostic efficacy of individual-versus-combined regional volumetrics in 2 commercially available brain volumetric software packages for predicting conversion of patients with mild cognitive impairment to Alzheimer disease. Data were obtained through the Alzheimer's Disease Neuroimaging Initiative. One hundred ninety-two subjects (mean age, 74.8 years; 39% female) diagnosed with mild cognitive impairment at baseline were studied. All had T1-weighted MR imaging sequences at baseline and 3-year clinical follow-up. Analysis was performed with NeuroQuant and Neuroreader. Receiver operating characteristic curves assessing the prognostic efficacy of each software package were generated by using a univariable approach using individual regional brain volumes and 2 multivariable approaches (multiple regression and random forest), combining multiple volumes. On univariable analysis of 11 NeuroQuant and 11 Neuroreader regional volumes, hippocampal volume had the highest area under the curve for both software packages (0.69, NeuroQuant; 0.68, Neuroreader) and was not significantly different ( P > .05) between packages. Multivariable analysis did not increase the area under the curve for either package (0.63, logistic regression; 0.60, random forest NeuroQuant; 0.65, logistic regression; 0.62, random forest Neuroreader). Of the multiple regional volume measures available in FDA-cleared brain volumetric software packages, hippocampal volume remains the best single predictor of conversion of mild cognitive impairment to Alzheimer disease at 3-year follow-up. Combining volumetrics did not add additional prognostic efficacy. Therefore, future prognostic studies in mild cognitive impairment, combining such tools with demographic and other biomarker measures, are justified in using hippocampal volume as the only volumetric biomarker. © 2017 by American Journal of Neuroradiology.

Intimate partner violence after the diagnosis of sexually transmitted diseases

PubMed Central

Andrade, Roumayne Fernandes Vieira; Araújo, Maria Alix Leite; Vieira, Luiza Jane Eyre de Souza; Reis, Cláudia Bastos Silveira; Miranda, Angélica Espinosa

2015-01-01

OBJECTIVE To assess the prevalence and factors associated with intimate partner violence after the diagnosis of sexually transmitted diseases. METHODS This cross-sectional study was conducted in Fortaleza, CE, Northeastern Brazil, in 2012 and involved 221 individuals (40.3% male and 59.7% female) attended to at reference health care units for the treatment of sexually transmitted diseases. Data were collected using a questionnaire applied during interviews with each participant. A multivariate analysis with a logistic regression model was conducted using the stepwise technique. Only the variables with a p value < 0.05 were included in the adjusted analysis. The odds ratio (OR) with 95% confidence interval (CI) was used as the measure of effect. RESULTS A total of 30.3% of the participants reported experiencing some type of violence (27.6%, psychological; 5.9%, physical; and 7.2%, sexual) after the diagnosis of sexually transmitted disease. In the multivariate analysis adjusted to assess intimate partner violence after the revelation of the diagnosis of sexually transmitted diseases, the following variables remained statistically significant: extramarital relations (OR = 3.72; 95%CI 1.91;7.26; p = 0.000), alcohol consumption by the partner (OR = 2.16; 95%CI 1.08;4.33; p = 0.026), history of violence prior to diagnosis (OR = 2.87; 95%CI 1.44;5.69; p = 0.003), and fear of disclosing the diagnosis to the partner (OR = 2.66; 95%CI 1.32;5.32; p = 0.006). CONCLUSIONS Individuals who had extramarital relations, experienced violence prior to the diagnosis of sexually transmitted disease, feared disclosing the diagnosis to the partner, and those whose partner consumed alcohol had an increased likelihood of suffering violence. The high prevalence of intimate partner violence suggests that this population is vulnerable and therefore intervention efforts should be directed to them. Referral health care services for the treatment of sexually transmitted diseases can be strategic places to identify and prevent intimate partner violence. PMID:25741656

TNFRSF10C copy number variation is associated with metastatic colorectal cancer

PubMed Central

Tanenbaum, Daniel G.; Hall, William A.; Colbert, Lauren E.; Bastien, Amanda J.; Brat, Daniel J.; Kong, Jun; Kim, Sungjin; Dwivedi, Bhakti; Kowalski, Jeanne; Landry, Jerome C.

2016-01-01

Background Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA). Methods Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status. Results TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13–10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42–42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016). Conclusions TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation therapy for rectal adenocarcinoma. PMID:27284460

Treatment of salivary gland neoplasms with fast neutron radiotherapy.

PubMed

Douglas, James G; Koh, Wui-jin; Austin-Seymour, Mary; Laramore, George E

2003-09-01

To evaluate the efficacy of fast neutron radiotherapy for the treatment of salivary gland neoplasms. Retrospective analysis. University of Washington Cancer Center, Neutron Facility, Seattle. The medical records of 279 patients treated with curative intent using fast neutron radiotherapy at the University of Washington Cancer Center were reviewed. Of the 279 patients, 263 had evidence of gross residual disease at the time of treatment (16 had no evidence of gross residual disease), 141 had tumors of a major salivary gland, and 138 had tumors of minor salivary glands. The median follow-up period was 36 months (range, 1-142 months). Local-regional control, cause-specific survival, and freedom from metastasis. The 6-year actuarial cause-specific survival rate was 67%. Multivariate analysis revealed that low group stage (I-II) disease, minor salivary sites, lack of skull base invasion, and primary disease were associated with a statistically significant improvement in cause-specific survival. The 6-year actuarial local-regional control rate was 59%. Multivariate analysis revealed size 4 cm or smaller, lack of base of skull invasion, prior surgical resection, and no previous radiotherapy to have a statistically significant improved local-regional control. Sixteen patients without evidence of gross residual disease had a 100% 6-year actuarial local-regional control. The 6-year actuarial freedom from metastasis rate was 64%. Factors associated with decreased development of systemic metastases included negative lymph nodes at the time of treatment and lack of base of skull involvement. The 6-year actuarial rate of development of grade 3 or 4 long-term toxicity (using the Radiation Therapy Oncology Group and European Organization for Research on the Treatment of Cancer criteria) was 10%. No patient experienced grade 5 toxic effects. Neuron radiotherapy is an effective treatment for patients with salivary gland neoplasms who have gross residual disease and achieves excellent local-regional control in patients without evidence of gross disease.

Multivariate synaptic and behavioral profiling reveals new developmental endophenotypes in the prefrontal cortex

PubMed Central

Iafrati, Jillian; Malvache, Arnaud; Gonzalez Campo, Cecilia; Orejarena, M. Juliana; Lassalle, Olivier; Bouamrane, Lamine; Chavis, Pascale

2016-01-01

The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice. Multivariate analysis of bootstrapped datasets revealed subgroups of phenotypic traits specific to each maturational epoch. The preeminence of synaptic AMPA/NMDA receptor content to pre-weaning and juvenile endophenotypes shifts to long-term potentiation and memory renewal during adolescence followed by NMDA-GluN2B synaptic content in adulthood. Strikingly, multivariate analysis shows that pharmacological rehabilitation of reelin haploinsufficient dysfunctions is mediated through induction of new endophenotypes rather than reversion to wild-type traits. By delineating previously unknown developmental endophenotypic sequences, we conceived a promising general strategy to disambiguate the molecular underpinnings of complex psychiatric disorders and for the rational design of pharmacotherapies in these disorders. PMID:27765946

Small artery elasticity predicts future cardiovascular events in chinese patients with angiographic coronary artery disease.

PubMed

Wan, Zhaofei; Liu, Xiaojun; Wang, Xinhong; Liu, Fuqiang; Liu, Weimin; Wu, Yue; Pei, Leilei; Yuan, Zuyi

2014-04-01

Arterial elasticity has been shown to predict cardiovascular disease (CVD) in apparently healthy populations. The present study aimed to explore whether arterial elasticity could predict CVD events in Chinese patients with angiographic coronary artery disease (CAD). Arterial elasticity of 365 patients with angiographic CAD was measured. During follow-up (48 months; range 6-65), 140 CVD events occurred (including 34 deaths). Univariate Cox analysis demonstrated that both large arterial elasticity and small arterial elasticity were significant predictors of CVD events. Multivariate Cox analysis indicated that small arterial elasticity remained significant. Kaplan-Meier analysis showed that the probability of having a CVD event/CVD death increased with a decrease of small arterial elasticity (P < .001, respectively). Decreased small arterial elasticity independently predicts the risk of CVD events in Chinese patients with angiographic CAD.

Disease severity and treatment requirements in familial inflammatory bowel disease.

PubMed

Ballester, María Pilar; Martí, David; Tosca, Joan; Bosca-Watts, Marta Maia; Sanahuja, Ana; Navarro, Pablo; Pascual, Isabel; Antón, Rosario; Mora, Francisco; Mínguez, Miguel

2017-08-01

Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors. Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed. 14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn's disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis. Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies-three-year observational study.

PubMed

Matsushita, Isao; Motomura, Hiraku; Seki, Eiko; Kimura, Tomoatsu

2017-07-01

The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p < 0.001, OR:24.85, 95%CI: 5.07-121.79) and disease activity at one year after treatment (p = 0.003, OR:3.34, 95%CI:1.50-7.46) as independent factors associated with the progression of joint damage. On the other hand, multivariate analysis for distal weight-bearing joints identified disease activity at one year after treatment (p < 0.001, OR:2.13, 95%CI:1.43-3.18) as an independent factor related to the progression of damage. Baseline Larsen grade was strongly associated with the progression of damage in the proximal weight-bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

Disease-specific definitions of vitamin D deficiency need to be established in autoimmune and non-autoimmune chronic diseases: a retrospective comparison of three chronic diseases.

PubMed

Broder, Anna R; Tobin, Jonathan N; Putterman, Chaim

2010-01-01

We compared the odds of vitamin D deficiency in three chronic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 2 diabetes (T2DM), adjusting for medications, demographics, and laboratory parameters, common to all three diseases. We also designed multivariate models to determine whether different factors are associated with vitamin D deficiency in different racial/ethnic groups. We identified all patients with non-overlapping diagnoses of SLE, RA, and T2DM, with 25-hydroxyvitamin D (25OHD) levels measured between 2000 and 2009. Vitamin D deficiency was defined as 25OHD levels <20 ng/ml, based on previously established definitions. Race/ethnicity was analyzed as African-American non-Hispanic (African-American), Hispanic non-African-American (Hispanic), and Other based on self report. We included 3,914 patients in the final analysis: 123 SLE, 100 RA, and 3,691 T2DM. Among African-Americans the frequency of vitamin D deficiency was 59% in SLE, 47% in RA, and 67% in T2DM. Among Hispanics the frequency of vitamin D deficiency was 67% in SLE, 50% in RA, and 59% in T2DM. Compared with the SLE group, the adjusted odds ratio of vitamin D deficiency was 1.1, 95% CI (0.62, 2.1) in the RA group, and 2.0, 95% CI (1.3, 3.1) in the T2DM group. In the multivariate analysis, older age, higher serum calcium and bisphosphonate therapy were associated with a lower odds of vitamin D deficiency in all three racial/ethnic groups: 1,330 African-American, 1,257 Hispanic, and 1,100 Other. T2DM, serum creatinine, and vitamin D supplementation were associated with vitamin D deficiency in some, but not all, racial/ethnic groups. Vitamin D deficiency is highly prevalent in our patients with SLE, RA, and T2DM. While the odds of vitamin D deficiency are similar in RA and SLE patients in a multivariate analysis, T2DM patients have much higher odds of being vitamin D deficient. Different demographic and laboratory factors may be associated with vitamin D deficiency within different racial/ethnic groups. Therefore, disease-specific and race/ethnicity-specific definitions of vitamin D deficiency need to be established in future studies in order to define goals of vitamin D replacement in patients with autoimmune and non-autoimmune chronic diseases.

Charlson comorbidity index as a predictor of periodontal disease in elderly participants

PubMed Central

2018-01-01

Purpose This study investigated the validity of the Charlson comorbidity index (CCI) as a predictor of periodontal disease (PD) over a 12-year period. Methods Nationwide representative samples of 149,785 adults aged ≥60 years with PD (International Classification of Disease, 10th revision [ICD-10], K052–K056) were derived from the National Health Insurance Service-Elderly Cohort during 2002–2013. The degree of comorbidity was measured using the CCI (grade 0–6), including 17 diseases weighted on the basis of their association with mortality, and data were analyzed using multivariate Cox proportional-hazards regression in order to investigate the associations of comorbid diseases (CDs) with PD. Results The multivariate Cox regression analysis with adjustment for sociodemographic factors (sex, age, household income, insurance status, residence area, and health status) and CDs (acute myocardial infarction, congestive heart failure, peripheral vascular disease, cerebral vascular accident, dementia, pulmonary disease, connective tissue disorders, peptic ulcer, liver disease, diabetes, diabetes complications, paraplegia, renal disease, cancer, metastatic cancer, severe liver disease, and human immunodeficiency virus [HIV]) showed that the CCI in elderly comorbid participants was significantly and positively correlated with the presence of PD (grade 1: hazard ratio [HR], 1.11; P<0.001; grade ≥2: HR, 1.12, P<0.001). Conclusions We demonstrated that a higher CCI was a significant predictor of greater risk for PD in the South Korean elderly population. PMID:29770238

Use of nitrates in ischemic heart disease.

PubMed

Giuseppe, Cocco; Paul, Jerie; Hans-Ulrich, Iselin

2015-01-01

Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the incidence of acute coronary syndromes, while data from another multivariate study indicate that they have positive effects. Because of methodological differences and open questions, the two studies cannot be compared. A study in Japanese patients with vasospastic angina has shown that, when compared with calcium antagonists, long-acting nitrates do not improve long-term prognosis and that the risk for cardiac adverse events increases with the combined therapy. We have many unanswered questions.

Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease

PubMed Central

Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Akita, Tomoyuki; Tanaka, Junko

2017-01-01

In patients with nonalcoholic fatty liver disease (NAFLD), prognosis and outcome, especially non‐liver‐related mortality, remain incompletely elucidated. We clarified the mortality from all causes in patients with NAFLD. A total of 4,073 patients with NAFLD diagnosed by ultrasonography were enrolled. We investigated the causes of death and analyzed the mortality from non‐liver‐related diseases according to the degrees of steatosis and fibrosis using the competing risk method. We used the NAFLD fibrosis score (NFS) to assess fibrosis severity and the ultrasonography fatty liver score to evaluate steatosis severity. The numbers of patients with NFS indicating low, intermediate, and high probabilities of advanced fibrosis were 2,451 (60.2%), 1,462 (35.9%), and 160 (3.9%), respectively. Of the 4,073 patients, 179 died during follow‐up, but only nine deaths were due to liver‐related diseases. Of the remaining 170 patients who died due to non‐liver‐related diseases, 83 (48.8%), 42 (24.7%), and 45 (26.5%) patients died due to malignancies, cerebrovascular and cardiovascular diseases, and benign diseases (excluding cerebrovascular and cardiovascular diseases), respectively. Multivariate analysis showed that the intermediate and high NFS groups were independently associated with each disease category: hazard ratio (HR) 2.163 (95% confidence interval [CI], 1.354‐3.457) and HR 4.814 (95% CI, 2.323‐9.977) for malignancies; HR 2.265 (95% CI, 1.141‐4.497) and HR 8.482 (95% CI, 3.558‐20.220) for cerebrovascular and cardiovascular diseases; and HR 3.216 (95% CI, 1.641‐6.303) and HR 5.558 (95% CI, 1.923‐16.070) for benign diseases, respectively. Conversely, the status of steatosis was not associated with risk of mortality in multivariate analysis. Conclusion: Progression of liver fibrosis severity was associated with mortality from various non‐liver‐related causes in patients with NAFLD. (Hepatology Communications 2017;1:928–945) PMID:29404500

FGWAS: Functional genome wide association analysis.

PubMed

Huang, Chao; Thompson, Paul; Wang, Yalin; Yu, Yang; Zhang, Jingwen; Kong, Dehan; Colen, Rivka R; Knickmeyer, Rebecca C; Zhu, Hongtu

2017-10-01

Functional phenotypes (e.g., subcortical surface representation), which commonly arise in imaging genetic studies, have been used to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. However, existing statistical methods largely ignore the functional features (e.g., functional smoothness and correlation). The aim of this paper is to develop a functional genome-wide association analysis (FGWAS) framework to efficiently carry out whole-genome analyses of functional phenotypes. FGWAS consists of three components: a multivariate varying coefficient model, a global sure independence screening procedure, and a test procedure. Compared with the standard multivariate regression model, the multivariate varying coefficient model explicitly models the functional features of functional phenotypes through the integration of smooth coefficient functions and functional principal component analysis. Statistically, compared with existing methods for genome-wide association studies (GWAS), FGWAS can substantially boost the detection power for discovering important genetic variants influencing brain structure and function. Simulation studies show that FGWAS outperforms existing GWAS methods for searching sparse signals in an extremely large search space, while controlling for the family-wise error rate. We have successfully applied FGWAS to large-scale analysis of data from the Alzheimer's Disease Neuroimaging Initiative for 708 subjects, 30,000 vertices on the left and right hippocampal surfaces, and 501,584 SNPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Climate variability, weather and enteric disease incidence in New Zealand: time series analysis.

PubMed

Lal, Aparna; Ikeda, Takayoshi; French, Nigel; Baker, Michael G; Hales, Simon

2013-01-01

Evaluating the influence of climate variability on enteric disease incidence may improve our ability to predict how climate change may affect these diseases. To examine the associations between regional climate variability and enteric disease incidence in New Zealand. Associations between monthly climate and enteric diseases (campylobacteriosis, salmonellosis, cryptosporidiosis, giardiasis) were investigated using Seasonal Auto Regressive Integrated Moving Average (SARIMA) models. No climatic factors were significantly associated with campylobacteriosis and giardiasis, with similar predictive power for univariate and multivariate models. Cryptosporidiosis was positively associated with average temperature of the previous month (β =  0.130, SE =  0.060, p <0.01) and inversely related to the Southern Oscillation Index (SOI) two months previously (β =  -0.008, SE =  0.004, p <0.05). By contrast, salmonellosis was positively associated with temperature (β  = 0.110, SE = 0.020, p<0.001) of the current month and SOI of the current (β  = 0.005, SE = 0.002, p<0.050) and previous month (β  = 0.005, SE = 0.002, p<0.05). Forecasting accuracy of the multivariate models for cryptosporidiosis and salmonellosis were significantly higher. Although spatial heterogeneity in the observed patterns could not be assessed, these results suggest that temporally lagged relationships between climate variables and national communicable disease incidence data can contribute to disease prediction models and early warning systems.

Texture analysis of pulmonary parenchymateous changes related to pulmonary thromboembolism in dogs - a novel approach using quantitative methods.

PubMed

Marschner, C B; Kokla, M; Amigo, J M; Rozanski, E A; Wiinberg, B; McEvoy, F J

2017-07-11

Diagnosis of pulmonary thromboembolism (PTE) in dogs relies on computed tomography pulmonary angiography (CTPA), but detailed interpretation of CTPA images is demanding for the radiologist and only large vessels may be evaluated. New approaches for better detection of smaller thrombi include dual energy computed tomography (DECT) as well as computer assisted diagnosis (CAD) techniques. The purpose of this study was to investigate the performance of quantitative texture analysis for detecting dogs with PTE using grey-level co-occurrence matrices (GLCM) and multivariate statistical classification analyses. CT images from healthy (n = 6) and diseased (n = 29) dogs with and without PTE confirmed on CTPA were segmented so that only tissue with CT numbers between -1024 and -250 Houndsfield Units (HU) was preserved. GLCM analysis and subsequent multivariate classification analyses were performed on texture parameters extracted from these images. Leave-one-dog-out cross validation and receiver operator characteristic (ROC) showed that the models generated from the texture analysis were able to predict healthy dogs with optimal levels of performance. Partial Least Square Discriminant Analysis (PLS-DA) obtained a sensitivity of 94% and a specificity of 96%, while Support Vector Machines (SVM) yielded a sensitivity of 99% and a specificity of 100%. The models, however, performed worse in classifying the type of disease in the diseased dog group: In diseased dogs with PTE sensitivities were 30% (PLS-DA) and 38% (SVM), and specificities were 80% (PLS-DA) and 89% (SVM). In diseased dogs without PTE the sensitivities of the models were 59% (PLS-DA) and 79% (SVM) and specificities were 79% (PLS-DA) and 82% (SVM). The results indicate that texture analysis of CTPA images using GLCM is an effective tool for distinguishing healthy from abnormal lung. Furthermore the texture of pulmonary parenchyma in dogs with PTE is altered, when compared to the texture of pulmonary parenchyma of healthy dogs. The models' poorer performance in classifying dogs within the diseased group, may be related to the low number of dogs compared to texture variables, a lack of balanced number of dogs within each group or a real lack of difference in the texture features among the diseased dogs.

Prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma: a SEER database analysis.

PubMed

Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Abdel-Rahman, Omar

2017-07-01

We the prognostic value of site-specific extra-hepatic disease in hepatocellular carcinoma (HCC) patients registered within the surveillance, epidemiology and end results (SEER) database. SEER database (2010-2013) has been queried through SEER*Stat program to determine the prognosis of advanced HCC patients according to the site of extra-hepatic disease. Survival analysis has been conducted through Kaplan Meier analysis. A total of 4396 patients with stage IV HCC were identified in the period from 2010-2013 and they were included into this analysis. Patients with isolated regional lymph node involvement have better outcomes compared to patients with any other site of extra-hepatic disease (P < 0.0001 for both endpoints). Among patients with distant metastases, patients with bone metastases have better outcomes compared to patients with lung metastases (P < 0.0001 for both endpoints). Multivariate analysis revealed that younger age, normal alpha fetoprotein, single site of extra-hepatic disease, local treatment to the primary tumor and surgery to the metastatic disease were associated with better overall survival and liver cancer-specific survival. Within the limits of the current SEER analysis, HCC patients with isolated lung metastases seem to have worse outcomes compared to patients with isolated bone or regional nodal metastases.​.

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study.

PubMed

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-05-26

BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

Novel risk score of contrast-induced nephropathy after percutaneous coronary intervention.

PubMed

Ji, Ling; Su, XiaoFeng; Qin, Wei; Mi, XuHua; Liu, Fei; Tang, XiaoHong; Li, Zi; Yang, LiChuan

2015-08-01

Contrast-induced nephropathy (CIN) post-percutaneous coronary intervention (PCI) is a major cause of acute kidney injury. In this study, we established a comprehensive risk score model to assess risk of CIN after PCI procedure, which could be easily used in a clinical environment. A total of 805 PCI patients, divided into analysis cohort (70%) and validation cohort (30%), were enrolled retrospectively in this study. Risk factors for CIN were identified using univariate analysis and multivariate logistic regression in the analysis cohort. Risk score model was developed based on multiple regression coefficients. Sensitivity and specificity of the new risk score system was validated in the validation cohort. Comparisons between the new risk score model and previous reported models were applied. The incidence of post-PCI CIN in the analysis cohort (n = 565) was 12%. Considerably high CIN incidence (50%) was observed in patients with chronic kidney disease (CKD). Age >75, body mass index (BMI) >25, myoglobin level, cardiac function level, hypoalbuminaemia, history of chronic kidney disease (CKD), Intra-aortic balloon pump (IABP) and peripheral vascular disease (PVD) were identified as independent risk factors of post-PCI CIN. A novel risk score model was established using multivariate regression coefficients, which showed highest sensitivity and specificity (0.917, 95%CI 0.877-0.957) compared with previous models. A new post-PCI CIN risk score model was developed based on a retrospective study of 805 patients. Application of this model might be helpful to predict CIN in patients undergoing PCI procedure. © 2015 Asian Pacific Society of Nephrology.

Drug development for exceptionally rare metabolic diseases: challenging but not impossible

PubMed Central

2013-01-01

Background We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Methods All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the ‘Orphanet database of Rare diseases’. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). Results In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). Conclusion For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest. PMID:24237580

The Assessment of Neurological Systems with Functional Imaging

ERIC Educational Resources Information Center

Eidelberg, David

2007-01-01

In recent years a number of multivariate approaches have been introduced to map neural systems in health and disease. In this review, we focus on spatial covariance methods applied to functional imaging data to identify patterns of regional activity associated with behavior. In the rest state, this form of network analysis can be used to detect…

Health Related Quality of Life among Insulin-Dependent Diabetics: Disease-Related and Psychosocial Correlates.

ERIC Educational Resources Information Center

Aalto, Anna-Mari; Uutela, Antti; Aro, Arja R.

1997-01-01

The associations of health and psychosocial factors with the Health Related Quality of Life Questionnaire were examined in adult type 1 diabetic patients (N=385). The most important factors from multivariate analysis were self-efficacy and diabetes-related social support, especially among those in good physical condition. Diabetes-specific factors…

Multivariate functional response regression, with application to fluorescence spectroscopy in a cervical pre-cancer study.

PubMed

Zhu, Hongxiao; Morris, Jeffrey S; Wei, Fengrong; Cox, Dennis D

2017-07-01

Many scientific studies measure different types of high-dimensional signals or images from the same subject, producing multivariate functional data. These functional measurements carry different types of information about the scientific process, and a joint analysis that integrates information across them may provide new insights into the underlying mechanism for the phenomenon under study. Motivated by fluorescence spectroscopy data in a cervical pre-cancer study, a multivariate functional response regression model is proposed, which treats multivariate functional observations as responses and a common set of covariates as predictors. This novel modeling framework simultaneously accounts for correlations between functional variables and potential multi-level structures in data that are induced by experimental design. The model is fitted by performing a two-stage linear transformation-a basis expansion to each functional variable followed by principal component analysis for the concatenated basis coefficients. This transformation effectively reduces the intra-and inter-function correlations and facilitates fast and convenient calculation. A fully Bayesian approach is adopted to sample the model parameters in the transformed space, and posterior inference is performed after inverse-transforming the regression coefficients back to the original data domain. The proposed approach produces functional tests that flag local regions on the functional effects, while controlling the overall experiment-wise error rate or false discovery rate. It also enables functional discriminant analysis through posterior predictive calculation. Analysis of the fluorescence spectroscopy data reveals local regions with differential expressions across the pre-cancer and normal samples. These regions may serve as biomarkers for prognosis and disease assessment.

MDAS: an integrated system for metabonomic data analysis.

PubMed

Liu, Juan; Li, Bo; Xiong, Jiang-Hui

2009-03-01

Metabonomics, the latest 'omics' research field, shows great promise as a tool in biomarker discovery, drug efficacy and toxicity analysis, disease diagnosis and prognosis. One of the major challenges now facing researchers is how to process this data to yield useful information about a biological system, e.g., the mechanism of diseases. Traditional methods employed in metabonomic data analysis use multivariate analysis methods developed independently in chemometrics research. Additionally, with the development of machine learning approaches, some methods such as SVMs also show promise for use in metabonomic data analysis. Aside from the application of general multivariate analysis and machine learning methods to this problem, there is also a need for an integrated tool customized for metabonomic data analysis which can be easily used by biologists to reveal interesting patterns in metabonomic data.In this paper, we present a novel software tool MDAS (Metabonomic Data Analysis System) for metabonomic data analysis which integrates traditional chemometrics methods and newly introduced machine learning approaches. MDAS contains a suite of functional models for metabonomic data analysis and optimizes the flow of data analysis. Several file formats can be accepted as input. The input data can be optionally preprocessed and can then be processed with operations such as feature analysis and dimensionality reduction. The data with reduced dimensionalities can be used for training or testing through machine learning models. The system supplies proper visualization for data preprocessing, feature analysis, and classification which can be a powerful function for users to extract knowledge from the data. MDAS is an integrated platform for metabonomic data analysis, which transforms a complex analysis procedure into a more formalized and simplified one. The software package can be obtained from the authors.

Generating Virtual Patients by Multivariate and Discrete Re-Sampling Techniques.

PubMed

Teutonico, D; Musuamba, F; Maas, H J; Facius, A; Yang, S; Danhof, M; Della Pasqua, O

2015-10-01

Clinical Trial Simulations (CTS) are a valuable tool for decision-making during drug development. However, to obtain realistic simulation scenarios, the patients included in the CTS must be representative of the target population. This is particularly important when covariate effects exist that may affect the outcome of a trial. The objective of our investigation was to evaluate and compare CTS results using re-sampling from a population pool and multivariate distributions to simulate patient covariates. COPD was selected as paradigm disease for the purposes of our analysis, FEV1 was used as response measure and the effects of a hypothetical intervention were evaluated in different populations in order to assess the predictive performance of the two methods. Our results show that the multivariate distribution method produces realistic covariate correlations, comparable to the real population. Moreover, it allows simulation of patient characteristics beyond the limits of inclusion and exclusion criteria in historical protocols. Both methods, discrete resampling and multivariate distribution generate realistic pools of virtual patients. However the use of a multivariate distribution enable more flexible simulation scenarios since it is not necessarily bound to the existing covariate combinations in the available clinical data sets.

Orthotopic Liver Transplantation in High-Risk Patients

PubMed Central

Gayowski, Timothy; Marino, Ignazio R.; Singh, Nina; Doyle, Howard; Wagener, Marilyn; Fung, John J.; Starzl, Thomas E.

2010-01-01

Background One of the most controversial areas in patient selection and donor allocation is the high-risk patient. Risk factors for mortality and major infectious morbidity were prospectively analyzed in consecutive United States veterans undergoing liver transplantation under primary tacrolimus-based immunosuppression. Methods Twenty-eight pre-liver transplant, operative, and posttransplant risk factors were examined univariately and multivariately in 140 consecutive liver transplants in 130 veterans (98% male; mean age, 47.3 years). Results Eighty-two percent of the patients had post-necrotic cirrhosis due to viral hepatitis or ethanol (20% ethanol alone), and only 12% had cholestatic liver disease. Ninety-eight percent of the patients were hospitalized at the time of transplantation (66% United Network for Organ Sharing [UNOS] 2, 32% UNOS 1). Major bacterial infection, posttransplant dialysis, additional immunosuppression, readmission to intensive care unit (P=0.0001 for all), major fungal infection, posttransplant abdominal surgery, posttransplant intensive care unit stay length of stay (P<0.005 for all), donor age, pretransplant dialysis, and creatinine (P<0.05 for all) were significantly associated with mortality by univariate analysis. Underlying liver disease, cytomegalovirus infection and disease, portal vein thrombosis, UNOS status, Childs-Pugh score, patient age, pretransplant bilirubin, ischemia time, and operative blood loss were not significant predictors of mortality. Patients with hepatitis C (HCV) and recurrent HCV had a trend towards higher mortality (P=0.18). By multivariate analysis, donor age, any major infection, additional immunosuppression, post-transplant dialysis, and subsequent transplantation were significant independent predictors of mortality (P<0.05). Major infectious morbidity was associated with HCV recurrence (P=0.003), posttransplant dialysis (P=0.001), pretransplant creatinine, donor age, median blood loss, intensive care unit length of stay, additional immunosuppression, and biopsy-proven rejection (P<0.05 for all). By multivariate analysis, intensive care unit length of stay and additional immunosuppression were significant independent predictors of infectious morbidity (P<0.03). HCV recurrence was of borderline significance (P=0.07). Conclusions Biologic and physiologic parameters appear to be more powerful predictors of mortality and morbidity after liver transplantation. Both donor and recipient variables need to be considered for early and late outcome analysis and risk assessment modeling. PMID:9500623

Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

PubMed

Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

2015-07-30

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2018-03-01

Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with cutaneous melanoma are needed. Surveillance, Epidemiology and End Results (SEER) database (2010-2013) has been explored through SEER*Stat program. For each of six distant metastatic sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous), relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis, and multivariate analysis has been conducted through a Cox proportional hazard model. A total of 2691 patients with metastatic cutaneous melanoma were identified in the period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases have the best overall and melanoma-specific survival (MSS) followed by patients with isolated distant lymph node metastases followed by patients with isolated lung metastases. Patients with isolated liver, bone, or brain metastases have the worst overall and MSS (p < .0001 for both end points). Multivariate analysis revealed that age more than 70 at diagnosis (p = .012); multiple sites of metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery to the metastatic disease (p < .0001) were associated with worse overall survival (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p < .0001), no surgery to the primary tumor (p < .0001), and no surgery to the metastatic disease (p < .0001) were associated with worse survival. The prognosis of metastatic cutaneous melanoma patients differs considerably according to the site of distant metastases. Further prospective studies are required to evaluate the role of local treatment in the management of metastatic disease.

Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

PubMed

Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-11-25

Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

Role of hepatic resection for patients with carcinoid heart disease.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Rubin, Joseph; Møller, Jacob E; Scott, Christopher G; Nagorney, David M; Pellikka, Patricia A

2008-02-01

To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005, we calculated survival from first diagnosis of cardiac involvement. Hepatic resection during follow-up was entered as a time-dependent covariable in a multivariable analysis. In patients with serial echocardiograms more than 1 year apart without intervening cardiac surgery, a previously validated cardiac severity score was calculated. A score increase that exceeded 25% was considered relevant progression. Hepatic resection was performed in 31 patients (12%) during follow-up. Five-year survival was significantly higher in these patients (86.5%; 95% confidence interval [CI], 73.5%-100.0%) than in patients without hepatic resection (29.0%; 95% CI, 23.3%-36.1%; univariable hazard ratio for hepatic resection, 0.25; 95% CI 0.12-0.53; P<.001). Hepatic resection remained strongly associated with improved prognosis in multivariable analysis (hazard ratio, 0.31; 95% CI, 0.14-0.66; P=.003). Among 77 patients (29%) with serial echocardiograms, 10 (13%) underwent hepatic resection during follow-up; resection was independently associated with decreased risk of cardiac progression (odds ratio, 0.29; 95% CI, 0.06-0.75; P=.03). Despite the limitations of this retrospective nonrandomized study, our data suggest that patients with carcinoid heart disease who undergo hepatic resection have decreased cardiac progression and improved prognosis. Eligible patients should be considered for hepatic surgery.

Oral candidiasis in systemic lupus erythematosus.

PubMed

Fangtham, M; Magder, L S; Petri, M A

2014-06-01

We assessed the frequency of oral candidiasis and the association between demographic variables, disease-related variables, corticosteroid treatment, other treatments and the occurrence of oral candidiasis in the Hopkins Lupus Cohort. In this large prospective cohort study of 2258 patients with systemic lupus erythematosus (SLE), demographic and clinical associates of oral candidiasis were estimated by univariate, multivariate and within-person regression models. There were 53,548 cohort visits. Oral candidiasis was diagnosed at 675 visits (1.25%) in 325 (14%) of the patients. In the multivariate analyses, oral candidiasis was associated with African-American ethnicity, SELENA-SLEDAI disease activity, high white blood cell count, a history of bacterial infection, prednisone use and immunosuppressive use. The urine protein by urine dip stick was higher in SLE patients with oral candidiasis. Considering only patients who had candidiasis at some visits in a 'within-person' analysis, candidiasis was more frequent in visits with higher SELENA-SLEDAI disease activity, high white blood cell count, proteinuria by urine dip stick, a history of bacterial infection and prednisone use. The use of hydroxychloroquine was associated with a lower risk of oral candidiasis, but was not statistically significant (p = 0.50) in the within-person analysis models. This study identified multiple risk factors for oral candidiasis in SLE. Inspection of the oral cavity for signs of oral candidiasis is recommended especially in SLE patients with active disease, proteinuria, high white blood cell count, taking prednisone, immunosuppressive drugs or antibiotics. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Dose-response effects for depression and Schizophrenia management on hospital utilization in Illinois Medicaid: a multivariate regression analysis.

PubMed

Berg, Gregory D; Donnelly, Shawn; Warnick, Kathleen; Medina, Wendie; Miller, Mary

2014-07-03

The prevalence of schizophrenia and depression in the United States is far higher among Medicaid recipients than in the general population. Individuals suffering from mental illness, including schizophrenia and depression, also have higher rates of emergency department utilization, which is costly and may not generate the positive health outcomes desired. Disease management programs strive to help individuals suffering from chronic illnesses better manage their condition(s) and seek health care in the appropriate settings. The objective of this manuscript is to estimate a dose-response impact on hospital inpatient and emergency room utilizations for any reason by Medicaid recipients with depression or schizophrenia who received disease management contacts. Multivariate regression analysis of panel data taken from administrative claims was conducted to test the hypothesis that increased contacts lower the likelihood of all-cause inpatient admissions and emergency room visits. Subjects included 6,274 members of Illinois' non-institutionalized Medicaid-only aged, blind or disabled population diagnosed with depression or schizophrenia. The statistical measure is the odds ratio. The odds ratio association is between the monthly utilization indicators and the number of contacts (doses) a member had for each particular disease management intervention. Higher numbers of intervention contacts for Medicaid recipients diagnosed with depression or schizophrenia were associated with statistically significant reductions in all-cause inpatient admissions and emergency room utilizations. There is a high correlation between depression and schizophrenia disease management contacts and lowered all-cause hospital inpatient and emergency room utilizations.

Target organ damage in hypertensive patients of different ethnic groups.

PubMed

Wolak, Talya; Anfanger, Sharon; Wolak, Arik; Furman, Tsilla; Abuara'ar, Touphic; Biton, Amnon; Pilpel, Dina; Paran, Esther

2007-03-20

Hypertension is associated with involvement of target organs which varies among the different ethnic groups. The multiplicity of the population in Israel offers an opportunity for evaluating target organ damage in hypertensive patients of different ethnic origins. Data were collected from the computerized medical files of hypertensive patients in primary care clinics. The analysis was done on 576 hypertensive patients: 138 Bedouins (Arab residents), 141 Sephardic Jews (immigrants from North Africa and the Middle East), 152 Asian-Indian Jews (immigrants from India) and 145 Ashkenazi Jews (immigrants from Europe and North and South America). In multivariable logistic regressions adjusted for known risk factors and ethnicity, the prevalence of cerebrovascular disease was the highest among the Asian-Indian Jews (OR=3.09, p value=0.009). Renal damage was highest among the Bedouins (OR=4.54, p value<0.0001) and Asian-Indian Jews (OR=2.88, p value=0.005). The differences in the prevalence of renal damage among the various ethnic groups were even more pronounced among patients without diabetes (OR=8.31, p value<0.0001 in Bedouins and OR=7.46, p value=0.001 in Asian-Indian Jews). The prevalence of ischemic heart disease did not differ significantly among the four ethnic groups. The prevalence of cerebrovascular and renal diseases are both significantly associated with ethnic origin of Asian-Indian Jews and Bedouins. However, the multivariate analysis shows that the prevalence of ischemic heart disease is not associated with ethnicity.

Longitudinal costs of caring for people with Alzheimer's disease.

PubMed

Gillespie, Paddy; O'Shea, Eamon; Cullinan, John; Buchanan, Jacqui; Bobula, Joel; Lacey, Loretto; Gallagher, Damien; Mhaolain, Aine Ni; Lawlor, Brian

2015-05-01

There has been an increasing interest in the relationship between severity of disease and costs in the care of people with dementia. Much of the current evidence is based on cross-sectional data, suggesting the need to examine trends over time for this important and growing cohort of the population. This paper estimates resource use and costs of care based on longitudinal data for 72 people with dementia in Ireland. Data were collected from the Enhancing Care in Alzheimer's Disease (ECAD) study at two time points: baseline and follow-up, two years later. Patients' dependence on others was measured using the Dependence Scale (DS), while patient function was measured using the Disability Assessment for Dementia (DAD) scale. Univariate and multivariate analysis were used to explore the effects of a range of variables on formal and informal care costs. Total costs of formal and informal care over six months rose from €9,266 (Standard Deviation (SD): 12,947) per patient at baseline to €21,266 (SD: 26,883) at follow-up, two years later. This constituted a statistically significant (p = 0.0014) increase in costs over time, driven primarily by an increase in estimated informal care costs. In the multivariate analysis, a one-point increase in the DS score, that is a one-unit increase in patient's dependence on others, was associated with a 19% increase in total costs (p = 0.0610). Higher levels of dependence in people with Alzheimer's disease are significantly associated with increased costs of informal care as the disease progresses. Formal care services did not respond to increased dependence in people with dementia, leaving it to families to fill the caring gap, mainly through increased supervision with the progress of disease.

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

PubMed

Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund; Aslam, Fawad; Khan, Nasim A; Jacobs, Johannes W G; Henrohn, Dan; Rasker, J J; Kauppi, Markku J; Lang, Hui-Chu; Mota, Licia M H; Aggarwal, Amita; Yamanaka, Hisahi; Badsha, Humeira; Gossec, Laure; Cutolo, Maurizio; Ferraccioli, Gianfranco; Gremese, Elisa; Bong Lee, Eun; Inanc, Nevsun; Direskeneli, Haner; Taylor, Peter; Huisman, Margriet; Alten, Rieke; Pohl, Christoph; Oyoo, Omondi; Stropuviene, Sigita; Drosos, Alexandrosos A; Kerzberg, Eduardo; Ancuta, Codorina; Mofti, Ayman; Bergman, Martin; Detert, Jaqueline; Selim, Zaraa I; Abda, Essam A; Rexhepi, Blerta; Sokka, Tuulikki

2014-01-01

The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

Correlation between ultrafiltration rate and phase angle measured by BIA in chronic kidney disease patients on regular hemodialysis

NASA Astrophysics Data System (ADS)

Nasution, B. R.; Lubis, A. R.

2018-03-01

Chronic Kidney Disease (CKD) patients with regular hemodialysis have high rates of morbidity and mortality that may be related to the hemodynamic effects of rapid UFR and low PhA value. In this study, we investigated whether high UFR is associated with a low value of PhA thus indirectly affect the risk of morbidity and mortality. UFR and Bioelectrical Impedance Analysis (BIA) examination on 92 subjects were recorded shortly after HD and analyzed by using Pearson correlation test. Multivariate analysis was also conducted to identify several factors that can affect the value of Phase angle. The number of HD regular CKD patients with PhA<4 based on the division of the UFR (cc/kg/h) <10, 10-13, ≥ 13, respectively were3, 10 and 6, whereas patients with ≥ 4 PhA <10, 10-13, ≥ 13respectively were 60, 11, and 2. The results showed a significant relationship between UFR with PhA. In CKD patients with regular HD, UFR has aninverse relationship with the value of PhA. After multivariate analysis, the UFR and the etiology of HD are still significantly affect the value of PhA. UFR optimal value in patients with CKD with regular HD is <10 cc/kg/h.

Palliative interventions for hepatocellular carcinoma patients: analysis of the National Cancer Database.

PubMed

Hammad, Abdulrahman Y; Robbins, Jared R; Turaga, Kiran K; Christians, Kathleen K; Gamblin, T Clark; Johnston, Fabian M

2017-01-01

Palliative therapies are provided to a subset of hepatocellular carcinoma (HCC) patients with the aim of providing symptomatic relief, better quality of life and improved survival. The present study sought to assess and compare the efficacy of different palliative therapies for HCC. The National Cancer Database (NCDB), a retrospective national database that captures approximately 70% of all patients treated for cancer in the US, was queried for patients with HCC who were deemed unresectable from 1998-2011. Patients were stratified by receipt of palliative therapy. Survival analysis was examined by log-rank test and Kaplan Meier curves, and a multivariate proportional hazards model was utilized to identify the predictors of survival. A total of 3,267 patients were identified; 287 (8.7%) received surgical palliation, 827 (25.3%) received radiotherapy (RT), 877 (26.8%) received chemotherapy, 1,067 (32.6%) received pain management therapy, while 209 (6.4%) received a combination of the previous three modalities. On multivariate analysis palliative RT was identified as a positive predictor of survival [hazards ratio (HR) 0.65; 95% CI, 0.50-0.83]. Stratifying by disease stage, palliative RT provided a significant survival benefit for patients with stage IV disease. Palliative RT appears to extend survival and should be considered for patients presenting with late stage HCC.

Effect of investigation intensity and treatment differences on prostate cancer survivor's physical symptoms, psychological well-being and health-related quality of life: a two country cross-sectional study.

PubMed

Gavin, Anna T; Donnelly, David; Donnelly, Conan; Drummond, Frances J; Morgan, Eileen; Gormley, Gerard J; Sharp, Linda

2016-12-19

To investigate effects on men's health and well-being of higher prostate cancer (PCa) investigation and treatment levels in similar populations. PCa survivors in Ireland where the Republic of Ireland (RoI) has a 50% higher PCa incidence than Northern Ireland (NI). A cross-sectional postal questionnaire was sent to PCa survivors 2-18 years post-treatment, seeking information about current physical effects of treatment, health-related quality of life (HRQoL; EORTC QLQ-C30; EQ-5D-5L) and psychological well-being (21 question version of the Depression, Anxiety and Stress Scale, DASS-21). Outcomes in RoI and NI survivors were compared, stratifying into 'late disease' (stage III/IV and any Gleason grade (GG) at diagnosis) and 'early disease' (stage I/II and GG 2-7). Responses were weighted by age, jurisdiction and time since diagnosis. Between-country differences were investigated using multivariate logistic and linear regression. 3348 men responded (RoI n=2567; NI n=781; reflecting population sizes, response rate 54%). RoI responders were younger; less often had comorbidities (45% vs 38%); were more likely to present asymptomatically (66%; 41%) or with early disease (56%; 35%); and less often currently used androgen deprivation therapy (ADT; 2%; 28%). Current prevalence of incontinence (16%) and impotence (56% early disease, 67% late disease) did not differ between RoI and NI. In early disease, only current bowel problems (RoI 12%; NI 21%) differed significantly in multivariate analysis. In late disease, NI men reported significantly higher levels of gynaecomastia (23% vs 9%) and hot flashes(41% vs 19%), but when ADT users were analysed separately, differences disappeared. For HRQoL, in multivariate analysis, only pain (early disease: RoI 11.1, NI 19.4) and financial difficulties (late disease: RoI 10.4, NI 7.9) differed significantly between countries. There were no significant between-country differences in DASS-21 or index ED-5D-5L score. Treatment side effects were commonly reported and increased PCa detection in RoI has left more men with these side effects. We recommended that men be offered a PSA test only after informed discussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

PubMed

Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro

2017-09-01

The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Association between thoracic aortic disease and inguinal hernia.

PubMed

Olsson, Christian; Eriksson, Per; Franco-Cereceda, Anders

2014-08-21

The study hypothesis was that thoracic aortic disease (TAD) is associated with a higher-than-expected prevalence of inguinal hernia. Such an association has been reported for abdominal aortic aneurysm (AAA) and hernia. Unlike AAA, TAD is not necessarily detectable with clinical examination or ultrasound, and there are no population-based screening programs for TAD. Therefore, conditions associated with TAD, such as inguinal hernia, are of particular clinical relevance. The prevalence of inguinal hernia in subjects with TAD was determined from nation-wide register data and compared to a non-TAD group (patients with isolated aortic stenosis). Groups were balanced using propensity score matching. Multivariable statistical analysis (logistic regression) was performed to identify variables independently associated with hernia. Hernia prevalence was 110 of 750 (15%) in subjects with TAD versus 29 of 301 (9.6%) in non-TAD, P=0.03. This statistically significant difference remained after propensity score matching: 21 of 159 (13%) in TAD versus 14 of 159 (8.9%) in non-TAD, P<0.001. Variables independently associated with hernia in multivariable analysis were male sex (odds ratio [OR] with 95% confidence interval [95% CI]) 3.4 (2.1 to 5.4), P<0.001; increased age, OR 1.02/year (1.004 to 1.04), P=0.014; and TAD, OR 1.8 (1.1 to 2.8), P=0.015. The prevalence of inguinal hernia (15%) in TAD is higher than expected in a general population and higher in TAD, compared to non-TAD. TAD is independently associated with hernia in multivariable analysis. Presence or history of hernia may be of importance in detecting TAD, and the association warrants further study. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Satisfaction with care: a study of parents of children with congenital heart disease and parents of children with other diseases.

PubMed

Lawoko, Stephen; Soares, Joaquim J F

2004-03-01

We compared parents of children with congenital heart disease (PCCHD, n=1092) with parents of children with other diseases (PCOD, n=112) regarding satisfaction with their children's care (SCC). We also examined the association between parental/patient characteristics and SCC. The parents completed a questionnaire about such areas as satisfaction with care, children's health status, and financial situation. The design was cross-sectional and data were gathered over 20 consecutive days. The univariate and multivariate analyses showed that PCCHD were more satisfied with their children's medical care and waiting period for treatment of their ill children than PCOD, although the difference was only modest. Furthermore, mothers were less satisfied with staff attitudes than fathers, with the lowest satisfaction among mothers of children with CHD. However, the multivariate analysis indicated that less satisfaction with care was more associated with decreasing child age, unemployment, financial burden of disease, social isolation and psychological distress than with children's diseases, their severity and parental gender. We corroborated some previous findings and may have provided new insights regarding determinants of SCC among parents. Interventions to improve SCC may need to address issues of parental psychological distress, socialization, and financial burden of illness. Possible ways of achieving this are discussed. Finally, research in a longitudinal format is needed to further scrutinize determinants of parental SCC.

Coexisting infectious diseases on admission as a risk factor for mechanical ventilation in patients with Guillain-Barré syndrome.

PubMed

Kobori, Shinichiro; Kubo, Tatsuhiko; Otani, Makoto; Muramatsu, Keiji; Fujino, Yoshihisa; Adachi, Hiroaki; Horiguchi, Hiromasa; Fushimi, Kiyohide; Matsuda, Shinya

2017-07-01

The aim of this study was to investigate patient characteristics on admission to hospital that increase the risk of subsequent mechanical ventilation (MV) use for patients with Guillain-Barré syndrome (GBS). We extracted data from the Japanese Diagnosis Procedure Combination (DPC) database for 4132 GBS patients admitted to hospital. Clinical characteristics of GBS patients with and without MV were compared. Multivariate logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of requirement for MV with coexisting infectious diseases, after adjustment for potential confounding variables, age, sex, hospital type, and ambulance transportation. In total, 281 patients required MV, and 493 patients had coexisting respiratory diseases on admission. After adjustment for covariates and stratification by coexisting respiratory diseases, multivariate logistic regression analysis revealed that coexisting cytomegaloviral (CMV) disease (OR 8.81; 95% CI, 2.34-33.1) and herpes simplex viral (HSV) infections (OR 4.83; 95% CI, 1.16-20.1) were significantly associated with the requirement for MV in the group without coexisting respiratory diseases. Our findings suggest that coexisting CMV and HSV infections on admission might be significantly associated with increased risk of respiratory failure in GBS patients. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Association between control to target blood pressures and healthy lifestyle factors among Japanese hypertensive patients: longitudinal data analysis from Fukushima Research of Hypertension (FRESH).

PubMed

Yokokawa, Hirohide; Goto, Aya; Sanada, Hironobu; Watanabe, Tsuyoshi; Felder, Robin A; Jose, Pedro A; Yasumura, Seiji

2014-01-01

To determine success rates in controlling target blood pressures longitudinally by measuring several factors, including lifestyle characteristics associated with uncontrolled blood pressures for target treatment goals. This prospective observational cohort study (September 2008-September 2010) collected information on blood pressure control status and healthy lifestyle factors listed in Breslow's seven health practices through medical records and self-administered questionnaires from 884 of the 1264 Japanese hypertensive patients initially registered in the FRESH study. Multivariate analysis adjusted for associated factors was performed to estimate the association between lifestyle change and "uncontrolled blood pressures" at the final follow-up survey. Median age and proportion of men were 73 years and 39.1%, respectively. All survey failure rates were 37.6% among non-elderly patients (<65 years of age) without diabetes mellitus or chronic kidney disease, and 35.0% among patients with these diseases or myocardial infarction. Maintaining a healthy lifestyle was a protective factor against uncontrolled blood pressures in multivariate analysis. Obesity and smoking status were associated with uncontrolled blood pressures, and exercise frequency was borderline significance. The number of participants with healthy responses for these factors remained relatively low during follow up. Our study revealed low rates of controlled blood pressures, especially in non-elderly patients without diabetes mellitus or chronic kidney disease, and patients with these diseases or myocardial infarction. Our data indicate the need to maintain a healthy lifestyle, in particular, ideal body weight and adequate exercise frequency, for better hypertension management according to treatment guidelines. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Utilization of surgical treatment for local and locoregional esophageal cancer: Analysis of the National Cancer Data Base.

PubMed

Taylor, Lauren J; Greenberg, Caprice C; Lidor, Anne O; Leverson, Glen E; Maloney, James D; Macke, Ryan A

2017-02-01

Previous studies have suggested that esophagectomy is severely underused for patients with resectable esophageal cancer. The recent expansion of endoscopic local therapies, advances in surgical techniques, and improved postoperative outcomes have changed the therapeutic landscape. The impact of these developments and evolving treatment guidelines on national practice patterns is unknown. Patients diagnosed with clinical stage 0 to III esophageal cancer were identified from the National Cancer Database (2004-2013). The receipt of potentially curative surgical treatment over time was analyzed, and multivariate logistic regression was used to identify factors associated with surgical treatment. The analysis included 52,122 patients. From 2004 to 2013, the overall rate of potentially curative surgical treatment increased from 36.4% to 47.4% (P < .001). For stage 0 disease, the receipt of esophagectomy decreased from 23.8% to 17.9% (P < .001), whereas the use of local therapies increased from 34.3% to 58.8% (P < .001). The use of surgical treatment increased from 43.4% to 61.8% (P < .001), from 36.1% to 45.0% (P < .001), and from 30.8% to 38.6% (P < .001) for patients with stage I, II, and III disease, respectively. In the multivariate analysis, divergent practice patterns and adherence to national guidelines were noted between academic and community facilities. The use of potentially curative surgical treatment has increased for patients with stage 0 to III esophageal cancer. The expansion of local therapies has driven increased rates of surgical treatment for early-stage disease. Although the increased use of esophagectomy for more advanced disease is encouraging, significant variation persists at the patient and facility levels. Cancer 2017;123:410-419. © 2016 American Cancer Society. © 2016 American Cancer Society.

Decoy receptor 3 is a prognostic factor in renal cell cancer.

PubMed

Macher-Goeppinger, Stephan; Aulmann, Sebastian; Wagener, Nina; Funke, Benjamin; Tagscherer, Katrin E; Haferkamp, Axel; Hohenfellner, Markus; Kim, Sunghee; Autschbach, Frank; Schirmacher, Peter; Roth, Wilfried

2008-10-01

Decoy receptor 3 (DcR3) is a soluble protein that binds to and inactivates the death ligand CD95L. Here, we studied a possible association between DcR3 expression and prognosis in patients with renal cell carcinomas (RCCs). A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples was generated. Decoy receptor 3 expression in tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3 expression on disease-specific survival and progression-free survival was assessed using univariate analysis and multivariate Cox regression analysis. Decoy receptor 3 serum levels were determined by ELISA. High DcR3 expression was associated with high-grade (P = .005) and high-stage (P = .048) RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P = .002) was significantly higher in the group with high DcR3 expression. Decoy receptor 3 expression correlated negatively with disease-specific survival (P < .001) and progression-free survival (P < .001) in univariate analyses. A multivariate Cox regression analysis retained DcR3 expression as an independent prognostic factor that outperformed the Karnofsky performance status. In patients with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%, whereas in patients with DcR3-negative tumors, the survival probability was 65% (P < .001). Moreover, DcR3 serum levels were significantly higher in patients with high-stage localized disease (P = .007) and metastatic disease (P = .001). DcR3 expression is an independent prognostic factor of RCC progression and mortality. Therefore, the assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies.

Analysis of surgical outcomes of diverticular disease of the colon.

PubMed

Miyaso, Hideaki; Iwakawa, Kazuhide; Kitada, Koji; Kimura, Yuji; Isoda, Kenta; Nishie, Manabu; Hamano, Ryosuke; Tokunaga, Naoyuki; Tsunemitsu, Yosuke; Ohtsuka, Shinya; Inagawaki, Masaru; Iwagaki, Hiromi

2012-01-01

We analyzed retrospectively the surgical outcomes of diverticular diseases of the colon at the surgical division of Fukuyama Medical Center. Data were collected from 39 patients who underwent surgery for diverticular disease at Fukuyama Medical Center. Thirty-nine patients were admitted between 2005 and 2010. The mean age of the 39 patients was 63.6 years. The collected data included patient demographics, patient history, type of surgery and complications. Patients were divided into 2 groups, Elective vs. Emergent group, right vs. left colon group and laparotomy vs. laparoscopic approach. Multivariate analysis of the logistic model of morbidity revealed a significantly higher rate in the left colon and the Cox proportional hazards model clearly showed fewer postoperative hospital days with the laparoscopic approach. Surgical procedures should be decided in reference to the particular clinical and pathological features of diverticular disease to gain an acceptable morbidity and mortality rates.

Merkel Cell Carcinoma: A Population Analysis on Survival.

PubMed

Sridharan, Vishwajith; Muralidhar, Vinayak; Margalit, Danielle N; Tishler, Roy B; DeCaprio, James A; Thakuria, Manisha; Rabinowits, Guilherme; Schoenfeld, Jonathan D

2016-10-01

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy. However, factors associated with disease presentation and outcomes remain uncertain, especially in light of recent changes in workup, such as sentinel lymph node biopsy. Therefore, this study used the SEER database to examine factors that could affect stage at presentation and treatment. We identified 4,543 patients and evaluated associations between sex, race, age, primary disease site, disease presentation, and treatment. We also used univariate and multivariate analyses to examine the effect of these factors on disease-specific survival (DSS) and overall survival (OS). We specifically conducted subgroup analyses on a more modern cohort of patients with MCC treated between 2006 and 2012. Male sex, older age, larger tumor size, and primary tumors of the scalp, neck, or trunk were associated with a higher burden of nodal disease. Multivariate predictors of worse DSS/OS in both the recent and overall cohort included age older than 75 years, number of lymph nodes involved, tumors greater than 5 cm, metastatic disease, or lack of radiation therapy. The number of involved nodes was the best predictor of DSS/OS. Associations with radiation therapy were most pronounced in patients with nodal disease and those not undergoing surgery. Sex, age, tumor size, and primary site of disease correlated with burden of nodal disease in MCC. Associations between disease presentation and treatment strategies such as radiation and DSS and OS have remained relatively constant in the modern era from 2006 to 2012 compared with findings from prior studies. Copyright © 2016 by the National Comprehensive Cancer Network.

Nailfold capillaroscopy in Behçet's disease, analysis of 128 patients.

PubMed

Movasat, Atusa; Shahram, Farhad; Carreira, Patricia E; Nadji, Abdolhadi; Akhlaghi, Maassoomeh; Naderi, Nassim; Davatchi, Fereydoun

2009-05-01

The aims of this study were to find the characteristics and prevalence of nailfold capillary changes in a large series of patients with Behçet's disease (BD) and to analyze their possible relation to other clinical characteristics of the disease. We performed nailfold capillaroscopy in 128 randomly selected patients fulfilling the international classification criteria for BD. Capillaroscopy was done in eight fingers with a x3.2 microscopy. All patients were questioned for history of Raynaud's phenomenon, ischemic ulcers, smoking, and hypertension. A computerized form including demographic, clinical, and para-clinical features was used to collect data. Univariate and multivariate logistic regressions were used to analyze the relation between capillaroscopic findings and disease characteristics. Odds ratio and a confidence interval at 95% (CI) were calculated for each item. The mean age of the patients was 37 +/- 10 years, and the male to female ratio was 1.56:1. Capillaroscopy was abnormal in 51 patients (40%, CI 8.5). Enlarged capillaries were seen in 33 patients (26%, CI 7.6), hemorrhages in 21 (16%, CI 6.4), and capillary loss only in one patient. In univariate logistic regression analysis, the presence of enlarged capillaries was associated with lower age at disease onset (OR = 0.9, CI 0.9-1; p = 0.04), hypertension (OR = 4.2, CI 1.5-11.4; p = 0.006), superficial phlebitis (OR = 5.5, CI 1.2-24.4; p = 0.03), and negative pathergy test (OR = 0.4, CI 0.2-0.9; p = 0.04). The presence of hemorrhages tended to be associated with articular symptoms (p = 0.05). Multivariate analysis also confirmed the association of enlarged capillaries with lower age at disease onset (p = 0.01), hypertension (p = 0.001), and superficial phlebitis (p = 0.03). Nailfold abnormalities, mainly enlarged capillaries, are frequent in patients with BD. Our results suggest that these abnormalities may be related to other vascular features of the disease such as superficial phlebitis, but it does not seem to confer special risk for any other specific clinical symptom of the disease.

Hierarchical multivariate covariance analysis of metabolic connectivity

PubMed Central

Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J

2014-01-01

Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI). PMID:25294129

Can a bank crisis break your heart?

PubMed Central

Stuckler, David; Meissner, Christopher M; King, Lawrence P

2008-01-01

Background To assess whether a banking system crisis increases short-term population cardiovascular mortality rates. Methods International, longitudinal multivariate regression analysis of cardiovascular disease mortality data from 1960 to 2002 Results A system-wide banking crisis increases population heart disease mortality rates by 6.4% (95% CI: 2.5% to 10.2%, p < 0.01) in high income countries, after controlling for economic change, macroeconomic instability, and population age and social distribution. The estimated effect is nearly four times as large in low income countries. Conclusion Banking crises are a significant determinant of short-term increases in heart disease mortality rates, and may have more severe consequences for developing countries. PMID:18197979

Subclinical Hypothyroidism after 131I-Treatment of Graves' Disease: A Risk Factor for Depression?

PubMed

Yu, Jing; Tian, Ai-Juan; Yuan, Xin; Cheng, Xiao-Xin

2016-01-01

Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.

Increased prevalence of third-degree atrioventricular block in patients with type II diabetes mellitus.

PubMed

Movahed, Mohammad-Reza; Hashemzadeh, Mehrtash; Jamal, M Mazen

2005-10-01

Diabetes mellitus (DM) is a major risk for cardiovascular disease and mortality. There is some evidence that third-degree atrioventricular (AV) block occurs more commonly in patients with DM. In this study, we evaluated any possible association between DM and third-degree AV block using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in a very large inpatient database. We used patient treatment files containing discharge diagnoses using ICD-9 codes of inpatient treatment from all Veterans Health Administration hospitals. The cohort was stratified using the ICD-9-CM code for DM (n = 293,124), a control group with hypertension but no DM (n = 552,623), and the ICD-9 code for third-degree AV block (426.0) and smoking (305.1, V15.82). We performed multivariate analysis adjusting for coronary artery disease, congestive heart failure, smoking, and hyperlipidemia. Continuous and binary variables were analyzed using chi2 and Fisher exact tests. Third-degree AV block diagnosis was present in 3,240 of DM patients (1.1%) vs 3,367 patients (0.6%) in the control group. Using multivariate analysis, DM remained strongly associated with third-degree AV block (odds ratio, 3.1; 95% confidential interval, 3.0 to 3.3; p < 0.0001). Third-degree AV block occurs significantly more in patients with DM. This finding may, in part, explain the high cardiovascular mortality in DM patients.

[Multivariate analysis of factors influencing the effect of radiosynovectomy].

PubMed

Farahati, J; Schulz, G; Wendler, J; Körber, C; Geling, M; Kenn, W; Schmeider, P; Reidemeister, C; Reiners, Chr

2002-04-01

In this prospective study, the time to remission after Radiosynovectomy (RSV) was analyzed and the influence of age, sex, underlying disease, type of joint, and duration of illness on the success rate of RSV was determined. A total number of 57 patients with rheumatoid arthritis (n = 33) and arthrosis (n = 21) with a total number of 130 treated joints (36 knee, 66 small and 28 medium-size joints) were monitored using visual analogue scales (VAS) from one week before RSV up to four to six months after RSV. The patients had to answer 3 times daily for pain intensity of the treated joint. The time until remission was determined according to the Kaplan-Meier survivorship function. The influence of the prognosis parameters on outcome of RSV was determined by multivariate discriminant analysis. After six months, the probability of pain relief of more than 20% amounted to 78% and was significantly dependent on the age of the patient (p = 0.02) and the duration of illness (p = 0.05), however not on sex (p = 0.17), underlying disease (p = 0.23), and type of joint (p = 0.69). Irrespective of sex, type of joint and underlying disease, a measurable pain relief can be achieved with RSV in 78% of the patients with synovitis, whereby effectiveness is decreasing with increasing age and progress of illness.

Cluster and Multiple Correspondence Analyses in Rheumatology: Paths to Uncovering Relationships in a Sea of Data.

PubMed

Han, Lu; Benseler, Susanne M; Tyrrell, Pascal N

2018-05-01

Rheumatic diseases encompass a wide range of conditions caused by inflammation and dysregulation of the immune system resulting in organ damage. Research in these heterogeneous diseases benefits from multivariate methods. The aim of this review was to describe and evaluate current literature in rheumatology regarding cluster analysis and correspondence analysis. A systematic review showed an increase in studies making use of these 2 methods. However, standardization in how these methods are applied and reported is needed. Researcher expertise was determined to be the main barrier to considering these approaches, whereas education and collaborating with a biostatistician were suggested ways forward. Copyright © 2018 Elsevier Inc. All rights reserved.

Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer

PubMed Central

Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A

2012-01-01

Background: The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Methods: Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Results: Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Conclusion: Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer. PMID:22294182

Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer.

PubMed

Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A

2012-02-28

The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer.

A Machine Learning Approach to Automated Gait Analysis for the Noldus Catwalk System.

PubMed

Frohlich, Holger; Claes, Kasper; De Wolf, Catherine; Van Damme, Xavier; Michel, Anne

2018-05-01

Gait analysis of animal disease models can provide valuable insights into in vivo compound effects and thus help in preclinical drug development. The purpose of this paper is to establish a computational gait analysis approach for the Noldus Catwalk system, in which footprints are automatically captured and stored. We present a - to our knowledge - first machine learning based approach for the Catwalk system, which comprises a step decomposition, definition and extraction of meaningful features, multivariate step sequence alignment, feature selection, and training of different classifiers (gradient boosting machine, random forest, and elastic net). Using animal-wise leave-one-out cross validation we demonstrate that with our method we can reliable separate movement patterns of a putative Parkinson's disease animal model and several control groups. Furthermore, we show that we can predict the time point after and the type of different brain lesions and can even forecast the brain region, where the intervention was applied. We provide an in-depth analysis of the features involved into our classifiers via statistical techniques for model interpretation. A machine learning method for automated analysis of data from the Noldus Catwalk system was established. Our works shows the ability of machine learning to discriminate pharmacologically relevant animal groups based on their walking behavior in a multivariate manner. Further interesting aspects of the approach include the ability to learn from past experiments, improve with more data arriving and to make predictions for single animals in future studies.

Prognostic implications of adhesion molecule expression in colorectal cancer.

PubMed

Seo, Kyung-Jin; Kim, Maru; Kim, Jeana

2015-01-01

Research on the expression of adhesion molecules, E-cadherin (ECAD), CD24, CD44 and osteopontin (OPN) in colorectal cancer (CRC) has been limited, even though CRC is one of the leading causes of cancer-related deaths. This study was conducted to evaluate the expression of adhesion molecules in CRC and to determine their relationships with clinicopathologic variables, and the prognostic significance. The expression of ECAD, CD24, CD44 and OPN was examined in 174 stage II and III CRC specimens by immunohistochemistry of TMA. Negative ECAD expression was significantly correlated with advanced nodal stage and poor tumor differentiation. Multivariate analysis showed that both negative expression of ECAD and positive expression of CD24 were independent prognostic factors for disease-free survival (DFS) in CRC patients (P<0.001, relative risk [RR] = 5.596, 95% CI = 2.712-11.549; P = 0.038, RR = 3.768, 95% CI = 1.077-13.185, respectively). However, for overall survival (OS), only ECAD negativity showed statistically significant results in multivariate analysis (P<0.001, RR = 4.819, 95% CI = 2.515-9.234). Positive expression of CD24 was associated with poor OS in univariate analysis but was of no prognostic value in multivariate analysis. In conclusion, our study suggests that among these four adhesion molecules, ECAD and CD24 expression can be considered independent prognostic factors. The role of CD44 and OPN may need further evaluation.

Prognostic implications of adhesion molecule expression in colorectal cancer

PubMed Central

Seo, Kyung-Jin; Kim, Maru; Kim, Jeana

2015-01-01

Research on the expression of adhesion molecules, E-cadherin (ECAD), CD24, CD44 and osteopontin (OPN) in colorectal cancer (CRC) has been limited, even though CRC is one of the leading causes of cancer-related deaths. This study was conducted to evaluate the expression of adhesion molecules in CRC and to determine their relationships with clinicopathologic variables, and the prognostic significance. The expression of ECAD, CD24, CD44 and OPN was examined in 174 stage II and III CRC specimens by immunohistochemistry of TMA. Negative ECAD expression was significantly correlated with advanced nodal stage and poor tumor differentiation. Multivariate analysis showed that both negative expression of ECAD and positive expression of CD24 were independent prognostic factors for disease-free survival (DFS) in CRC patients (P<0.001, relative risk [RR] = 5.596, 95% CI = 2.712-11.549; P = 0.038, RR = 3.768, 95% CI = 1.077-13.185, respectively). However, for overall survival (OS), only ECAD negativity showed statistically significant results in multivariate analysis (P<0.001, RR = 4.819, 95% CI = 2.515-9.234). Positive expression of CD24 was associated with poor OS in univariate analysis but was of no prognostic value in multivariate analysis. In conclusion, our study suggests that among these four adhesion molecules, ECAD and CD24 expression can be considered independent prognostic factors. The role of CD44 and OPN may need further evaluation. PMID:26097606

Prolonged remission in Caucasian patients with SLE: prevalence and outcomes.

PubMed

Zen, Margherita; Iaccarino, Luca; Gatto, Mariele; Bettio, Silvano; Nalotto, Linda; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

2015-12-01

To assess the prevalence of prolonged remission in Caucasian patients affected with systemic lupus erythematosus (SLE) and its relationship with damage accrual. Caucasian patients diagnosed with SLE between 1990 and 2009 and quarterly seen from 2009 to 2013 were included in the study. We defined remission as prolonged when lasting ≥5 consecutive years. Three levels of remission were defined using the SLE Disease Activity Index-2000 (SLEDAI-2K): complete remission: no disease activity in corticosteroid-free and immunosuppressant-free patients; clinical remission off corticosteroids: serologically active clinical quiescent (SACQ) disease in corticosteroid-free patients and clinical remission on corticosteroids: SACQ disease in patients taking prednisone 1-5 mg/day. Damage was measured by the SLICC/American College of Rheumatology Damage Index (SDI). 224 patients fulfilled inclusion criteria: 196 (87.5%) were women, mean±SD disease duration 11.2±6.8 years. During the 5-year follow-up, 16 patients (7.1%) achieved prolonged complete remission, 33 (14.7%) prolonged clinical remission off corticosteroids and 35 (15.6%) prolonged clinical remission on corticosteroids. At the multivariate analysis, vasculitis (OR 4.95), glomerulonephritis (OR 2.38) and haematological manifestations (OR 2.19) over the patients' disease course were associated with an unremitted disease. SDI increased more frequently in unremitted (72/140, 51.4%) than in remitted patients (22/84, 26.2%; p=0.001); SDI median increase was higher in unremitted than in remitted patients: 1 (0-3) vs 0 (0-2), respectively (p<0.001). At multivariate analysis, unremitted disease (OR 2.52) and high-dose corticosteroid intake (OR 2.35) were risk factors for damage accrual. Thirty-seven percent of our Caucasian patients achieved a prolonged remission, which was associated with a better outcome in terms of damage accrual. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy.

PubMed

Bruzzese, Vincenzo; Zullo, Angelo; Picchianti Diamanti, Andrea; Ridola, Lorenzo; Lorenzetti, Roberto; Marrese, Cinzia; Scolieri, Palma; De Francesco, Vincenzo; Hassan, Cesare; Migliore, Alberto; Laganà, Bruno

2016-09-01

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21-29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.

Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases.

PubMed

Hirata, Makoto; Kamatani, Yoichiro; Nagai, Akiko; Kiyohara, Yutaka; Ninomiya, Toshiharu; Tamakoshi, Akiko; Yamagata, Zentaro; Kubo, Michiaki; Muto, Kaori; Mushiroda, Taisei; Murakami, Yoshinori; Yuji, Koichiro; Furukawa, Yoichi; Zembutsu, Hitoshi; Tanaka, Toshihiro; Ohnishi, Yozo; Nakamura, Yusuke; Matsuda, Koichi

2017-03-01

To implement personalized medicine, we established a large-scale patient cohort, BioBank Japan, in 2003. BioBank Japan contains DNA, serum, and clinical information derived from approximately 200,000 patients with 47 diseases. Serum and clinical information were collected annually until 2012. We analyzed clinical information of participants at enrollment, including age, sex, body mass index, hypertension, and smoking and drinking status, across 47 diseases, and compared the results with the Japanese database on Patient Survey and National Health and Nutrition Survey. We conducted multivariate logistic regression analysis, adjusting for sex and age, to assess the association between family history and disease development. Distribution of age at enrollment reflected the typical age of disease onset. Analysis of the clinical information revealed strong associations between smoking and chronic obstructive pulmonary disease, drinking and esophageal cancer, high body mass index and metabolic disease, and hypertension and cardiovascular disease. Logistic regression analysis showed that individuals with a family history of keloid exhibited a higher odds ratio than those without a family history, highlighting the strong impact of host genetic factor(s) on disease onset. Cross-sectional analysis of the clinical information of participants at enrollment revealed characteristics of the present cohort. Analysis of family history revealed the impact of host genetic factors on each disease. BioBank Japan, by publicly distributing DNA, serum, and clinical information, could be a fundamental infrastructure for the implementation of personalized medicine. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The Risk of Dupuytren Diagnosis in Obese Individuals.

PubMed

Hacquebord, Jacques H; Chiu, Vicki Y; Harness, Neil G

2017-03-01

Dupuytren disease is a common benign fibroproliferative disorder causing thickening and shortening of the palmar fascia of the hand. The exact etiology of the disease is unclear but known risk factors such as increased age, male sex, and northern European ethnicity have been established. A link between body mass index (BMI) and Dupuytren disease has not been established previously. The purpose of this study was to test the hypothesis that lower BMI is associated with increased risk for Dupuytren disease diagnosis. After we obtained institutional review board approval, we performed a retrospective review using an electronic medical record and an administrative database from Kaiser Permanente Southern California to identify all enrolled patients there between 2007 and 2014 who were diagnosed with Dupuytren disease. Basic demographic data including age, sex, ethnicity, and BMI were collected. Bivariate and multivariable logistical regression analyses were performed to evaluate for associations between Dupuytren disease and BMI. A total of 2,049,803 patients aged 18 years and older were enrolled in Kaiser Permanente Southern California from 2007 to 2014. During that period, 14,844 patients were identified as having Dupuytren disease. The data were consistent with well-defined demographic trends in Dupuytren disease, with increased rates seen in males, Caucasians, and patients aged 50 years and older. In the multivariable analysis, when controlling for age, race, and sex, the risk of Dupuytren disease was inversely proportional to BMI. The current study showed that higher BMI is associated with decreased odds of having Dupuytren disease. Further work will be required to determine the cause for the apparent relationship between Dupuytren disease and BMI and whether physiologic factors related to obesity may be protective against the development of Dupuytren disease. Prognostic II. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Multivariate spatial models of excess crash frequency at area level: case of Costa Rica.

PubMed

Aguero-Valverde, Jonathan

2013-10-01

Recently, areal models of crash frequency have being used in the analysis of various area-wide factors affecting road crashes. On the other hand, disease mapping methods are commonly used in epidemiology to assess the relative risk of the population at different spatial units. A natural next step is to combine these two approaches to estimate the excess crash frequency at area level as a measure of absolute crash risk. Furthermore, multivariate spatial models of crash severity are explored in order to account for both frequency and severity of crashes and control for the spatial correlation frequently found in crash data. This paper aims to extent the concept of safety performance functions to be used in areal models of crash frequency. A multivariate spatial model is used for that purpose and compared to its univariate counterpart. Full Bayes hierarchical approach is used to estimate the models of crash frequency at canton level for Costa Rica. An intrinsic multivariate conditional autoregressive model is used for modeling spatial random effects. The results show that the multivariate spatial model performs better than its univariate counterpart in terms of the penalized goodness-of-fit measure Deviance Information Criteria. Additionally, the effects of the spatial smoothing due to the multivariate spatial random effects are evident in the estimation of excess equivalent property damage only crashes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optical assay for biotechnology and clinical diagnosis.

PubMed

Moczko, Ewa; Cauchi, Michael; Turner, Claire; Meglinski, Igor; Piletsky, Sergey

2011-08-01

In this paper, we present an optical diagnostic assay consisting of a mixture of environmental-sensitive fluorescent dyes combined with multivariate data analysis for quantitative and qualitative examination of biological and clinical samples. The performance of the assay is based on the analysis of spectrum of the selected fluorescent dyes with the operational principle similar to electronic nose and electronic tongue systems. This approach has been successfully applied for monitoring of growing cell cultures and identification of gastrointestinal diseases in humans.

Intake of Fiber and Nuts during Adolescence and Incidence of Proliferative Benign Breast Disease

PubMed Central

Su, Xuefen; Tamimi, Rulla M.; Collins, Laura C.; Baer, Heather J.; Cho, Eunyoung; Sampson, Laura; Willett, Walter C.; Schnitt, Stuart J.; Connolly, James L.; Rosner, Bernard A.; Colditz, Graham A.

2011-01-01

Objective We examined the association between adolescent fiber intake and proliferative BBD, a marker of increased breast cancer risk, in the Nurses’ Health Study II. Methods Among 29,480 women who completed a high school diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD (multivariate HR (95% CI): 0.75 (0.59, 0.96), p-trend = 0.01) than women in the lowest quintile. High school intake of nuts and apples was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk (multivariate HR (95% CI): 0.64 (0.48, 0.85), p-trend < 0.01) than women consuming <1 serving/month. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the high school diet questionnaire. Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influence subsequent risk of breast disease and may suggest a viable means for breast cancer prevention. PMID:20229245

Information on co-morbidities collected by history is useful for assigning Otitis Media risk to children.

PubMed

Casselbrant, Margaretha L; Mandel, Ellen M; Doyle, William J

2016-06-01

Determine if a 2-Step multivariate analysis of historical symptom/sign data for comorbid diseases can abstract high-level constructs useful in assigning a child's "risk" for different Otitis Media expressions. Seventeen items related to the symptom/sign expression of hypothesized Otitis Media comorbidities were collected by history on 141 3-year-old children. Using established criteria, the children were assigned to 1 of 3 groups: Control (no significant past Otitis Media, n=45), Chronic Otitis Media with Effusion (n=45) and Recurrent Acute Otitis Media (n=51). Principal Component Analysis was used to identify factors representing the non-redundant shared information among related items and Discriminant Analysis operating on those factors was used to estimate the best predictor equation for pairwise group assignments. Six multivariate factors representing the assignable comorbidities of frequent colds, nasal allergy, gastroesophageal disease (specific and general), nasal congestion and asthma were identified and explained 81% of the variance in the 17 items. Discriminant Analysis showed that, for the Control-Chronic Otitis Media with Effusion comparison, a combination of 3 factors and, for the Control-Recurrent Acute Otitis Media comparison, a combination of 2 factors had assignment accuracies of 74% and 68%, respectively. For the contrast between the two disease expressions, a 2-factor combination had an assignment accuracy of 61%. These results show that this analytic methodology can abstract high-level constructs, comorbidities, from low-level data, symptom/sign scores, support a linkage between certain comorbidities and Otitis Media risk and suggest that specific comorbidity combinations contain information relevant to assigning the risk for different Otitis Media expressions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Colorectal specialization and survival in colorectal cancer.

PubMed

Hall, G M; Shanmugan, S; Bleier, J I S; Jeganathan, A N; Epstein, A J; Paulson, E C

2016-02-01

It is recognized that higher surgeon volume is associated with improved survival in colorectal cancer. However, there is a paucity of national studies that have evaluated the relationship between surgical specialization and survival. We used the Surveillance, Epidemiology, and End Results Medicare cancer registry to examine the association between colorectal specialization (CRS) and disease-specific survival (DSS) between 2001 and 2009. A total of 21,432 colon cancer and 5893 rectal cancer patients who underwent elective surgical resection between 2001 and 2009 were evaluated. Univariate and multivariate Cox survival analysis was used to identify the association between surgical specialization and cancer-specific survival. Colorectal specialists performed 16.3% of the colon and 27% of the rectal resections. On univariate analysis, specialization was associated with improved survival in Stage II and Stage III colon cancer and Stage II rectal cancer. In multivariate analysis, however, CRS was associated with significantly improved DSS only in Stage II rectal cancer [hazard ratio (HR) 0.70, P = 0.03]. CRS was not significantly associated with DSS in either Stage I (colon HR 1.14, P = 0.39; rectal HR 0.1.26, P = 0.23) or Stage III (colon HR 1.06, P = 0.52; rectal HR 1.08, P = 0.55) disease. When analysis was limited to high volume surgeons only, the relationship between CRS and DSS was unchanged. CRS is associated with improved DSS following resection of Stage II rectal cancer. A combination of factors may contribute to long-term survival in these patients, including appropriate surgical technique, multidisciplinary treatment decisions and guideline-adherent surveillance. CRS probably contributes positively to these factors resulting in improved survival. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Economic Impact of Increased Utilization of Multivariate Assay Testing to Guide the Treatment of Ovarian Cancer: Implications for Payers.

PubMed

Brodsky, Burton S; Owens, Gary M; Scotti, Dennis J; Needham, Keith A; Cool, Christina L

2017-10-01

Ovarian cancer is the eighth most common cancer among women, but ranks fifth in cancer-related causes of death, the majority of which are detected in late stages, after the cancer has metastasized. The CA125 test is the standard of care for assessing suspicious pelvic masses. However, the primary use of CA125 is to monitor treatment progress rather than to screen for disease, and its sensitivity is exceedingly low, unlike the multivariate assay OVA1. A cost-effective treatment of ovarian cancer requires early and accurate diagnosis of pelvic masses and reduced referrals of patients with benign tumors to a gynecologic oncologist. To analyze the economic impact of increased utilization of a multivariate assay, such as OVA1, to guide the treatment of ovarian cancer. The study population was drawn from Medicare and commercial health plan claims data. A budget impact model was constructed to estimate the economic consequences of substituting the multivariate assay OVA1 to replace the single biomarker assay CA125 to assess the likelihood of pelvic mass malignancy in premenopausal and/or postmenopausal women. All patients selected for the analysis had CA125 testing before surgical intervention. A total of 92,843 health plan members were included for analysis, comprising 48,113 commercially insured members and 44,730 Medicare beneficiaries. Estimates of future health plan expenditures, which were calculated from base-case assumptions, projected overall savings of $0.05 per-member per-month (PMPM) for commercially insured members and $0.01 PMPM for Medicare beneficiaries as a result of increased utilization of OVA1. Sensitivity analysis revealed potential savings of up to $0.17 PMPM for commercially insured patients and up to $0.05 for Medicare beneficiaries. The results of the budget impact model support the use of OVA1 instead of CA125 by indicating that modest cost-savings can be achieved, while reaping the clinical benefits of improved diagnostic accuracy, early disease detection, and reductions in multiple, and possibly unnecessary, referrals to gynecologic oncologists.

Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks' gestation.

PubMed

Witlin, A G; Saade, G R; Mattar, F; Sibai, B M

2000-03-01

We sought to characterize predictors of neonatal outcome in women with severe preeclampsia or eclampsia who were delivered of their infants preterm. We performed a retrospective analysis of 195 pregnancies delivered between 24 and 33 weeks' gestation because of severe preeclampsia or eclampsia. Multiple logistic regression and univariate chi(2) analysis were performed for the dependent outcome variables of survival and respiratory distress syndrome by use of independent fetal and maternal variables. A P value of <.05 was considered significant. In the multivariate analysis, respiratory distress syndrome was inversely related to gestational age at delivery (P =.0018) and directly related to cesarean delivery (P =.02), whereas survival was directly related to birth weight (P =.00025). There was no correlation in the multivariate analysis between respiratory distress syndrome or survival and corticosteroid use, composite neonatal morbidity, mean arterial pressure, eclampsia, or abruptio placentae. In the univariate analysis respiratory distress syndrome was associated with cesarean delivery (odds ratio, 7.19; 95% confidence interval, 2. 91-18.32). The incidence of intrauterine growth restriction increased as gestational age advanced. Furthermore, intrauterine growth restriction decreased survival in both the multivariate (P =. 038; odds ratio, 13.2; 95% confidence interval, 1.16-151.8) and univariate (P =.001; odds ratio, 5.88; 95% confidence interval, 1. 81-19.26) analyses. The presence of intrauterine growth restriction adversely affected survival independently of other variables. Presumed intrauterine stress, as reflected by the severity of maternal disease, did not improve neonatal outcome.

Insulin resistance, diabetes mellitus and thyroid dysfunction in patients with palmoplantar pustulosis: a case-controlled study.

PubMed

Ataş, Hatice; Gönül, Müzeyyen

2017-06-01

Palmoplantar pustulosis (PPP) is a chronic pustular inflammatory skin disease; however, its pathogenesis is not well understood. Several factors, such as genetics, tobacco use and autoimmune issues, may contribute to this disease. This research was conducted to investigate the relationships between insulin resistance, thyroid disease and PPP. Thirty-three patients with PPP and 27 age- and gender-matched controls were analysed for their smoking histories, thyroid function tests, anti-thyroid peroxidase antibody (anti-TPO) levels, fasting glucose, fasting insulin levels and the homeostatic model assessment (HOMA) index for insulin resistance. We found significant differences between the PPP and control groups according to their tobacco use and anti-TPO levels ( p = 0.009 and p = 0.009, respectively). The proportion of tobacco use was 90% in the PPP patients and 63% in the controls. Gender and tobacco use were predictive risk factors for PPP in the multivariate analysis ( OR = 141.7, p < 0.0001 and OR = 147.6, p = 0.006, respectively). An anti-TPO level > 35 U/ml and the presence of a thyroid abnormality were independent risk factors in the univariate, but not the multivariate analysis ( OR = 4.2, p = 0.025 and OR = 5.4, p = 0.004, respectively). A moderate correlation between the gender and anti-TPO level was found ( r = 0.361, p = 0.039); however, the fasting glucose, insulin and HOMA index were not significant between the PPP and control groups. Female gender and smoking were the most important risk factors for PPP; however, the increase in the anti-TPO level may be related to the predominance of females afflicted with this disease. Additional studies are necessary to clarify the relationships between PPP, thyroid disease and diabetes mellitus.

Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal.

PubMed

Agar, Nita Sally; Wedgeworth, Emma; Crichton, Siobhan; Mitchell, Tracey J; Cox, Michael; Ferreira, Silvia; Robson, Alistair; Calonje, Eduardo; Stefanato, Catherine M; Wain, Elizabeth Mary; Wilkins, Bridget; Fields, Paul A; Dean, Alan; Webb, Katherine; Scarisbrick, Julia; Morris, Stephen; Whittaker, Sean J

2010-11-01

We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

Bayesian inference on risk differences: an application to multivariate meta-analysis of adverse events in clinical trials.

PubMed

Chen, Yong; Luo, Sheng; Chu, Haitao; Wei, Peng

2013-05-01

Multivariate meta-analysis is useful in combining evidence from independent studies which involve several comparisons among groups based on a single outcome. For binary outcomes, the commonly used statistical models for multivariate meta-analysis are multivariate generalized linear mixed effects models which assume risks, after some transformation, follow a multivariate normal distribution with possible correlations. In this article, we consider an alternative model for multivariate meta-analysis where the risks are modeled by the multivariate beta distribution proposed by Sarmanov (1966). This model have several attractive features compared to the conventional multivariate generalized linear mixed effects models, including simplicity of likelihood function, no need to specify a link function, and has a closed-form expression of distribution functions for study-specific risk differences. We investigate the finite sample performance of this model by simulation studies and illustrate its use with an application to multivariate meta-analysis of adverse events of tricyclic antidepressants treatment in clinical trials.

B-mode sonographic criteria for differential diagnosis of cervicofacial lymphadenopathy in cat-scratch disease and toxoplasmosis.

PubMed

Ridder, Gerd Jürgen; Boedeker, Carsten Christof; Lee, Tao-Kwang Kevin; Sander, Anna

2003-04-01

Our purpose was to evaluate different sonographic parameters of cervicofacial lymphadenopathy caused by cat-scratch disease (CSD) and toxoplasmosis. By use of high-resolution B-mode sonography a total of 552 lymph nodes in the head and neck were detected between January 1997 and December 2001. There were 71 patients (422 lymph nodes) with CSD and 19 patients (130 lymph nodes) with toxoplasmosis. Sonographic variables, including 20 sonomorphologic features along with age and gender, were analyzed with multivariate logistic regression. Heterogenous lymph nodes were more often found in CSD (p =.003), and nonsharp nodal borders showed a significant association with CSD (p =.0005). Multivariate analysis identified sharpness of borders (p =.0001), S/L ratio (p =.0006), and type of lymphadenopathy (acute, abscessed, chronic) (p =.0006) as most significant for differentiating between CSD and toxoplasmosis. These results provide significant and useful criteria for ultrasonographic differentiation between CSD and toxoplasmosis. Copyright 2003 Wiley Periodicals, Inc.

Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

PubMed Central

Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

2009-01-01

Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors.

PubMed

Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

2014-12-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Strain of ascending aorta on cardiac magnetic resonance in 1027 patients: Relation with age, gender, and cardiovascular disease.

PubMed

Scarabello, Marco; Codari, Marina; Secchi, Francesco; Cannaò, Paola M; Alì, Marco; Di Leo, Giovanni; Sardanelli, Francesco

2018-02-01

To evaluate ascending aortic strain (AAS) with cardiac magnetic resonance (CMR) in a large consecutive series of patients with different types of cardiovascular disease (CVD). Two-dimensional phase-contrast gradient-echo sequences of the ascending aorta were retrospectively reviewed in 1027 patients (726 males, 301 females). Aortic lumen area was segmented using a semi-automatic approach to calculate AAS values. Subgroup analysis was performed for patients with normal CMR, tetralogy of Fallot (ToF), and ischemic heart disease (IHD). Multivariate and post-hoc analyses were performed to evaluate the effect of age, gender, and CVD on AAS values. Shapiro-Wilk, three- and two-way ANOVA, Mann-Whitney U, and Spearman correlation statistics were used. Multivariate analysis showed significant differences in AAS among decades of age (p<0.001), genders (p=0.006) and CVD subgroups (p<0.001) without interaction among these factors. A gender-related difference (higher AAS in females) was significant in ToF (p=0.008), while an AAS reduction during aging was observed in all CVD subgroups. Post-hoc analysis showed a significantly lower AAS in ToF and IHD patients compared to subjects with normal CMR (p<0.001). Differences in age, gender, and CVD independently affect AAS. The lower AAS observed in ToF fosters its assessment during follow-up in adulthood. Future studies on causes and clinical implications of a higher AAS in females affected by ToF are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

PubMed

Hamilton, C A; Miller, A; Casablanca, Y; Horowitz, N S; Rungruang, B; Krivak, T C; Richard, S D; Rodriguez, N; Birrer, M J; Backes, F J; Geller, M A; Quinn, M; Goodheart, M J; Mutch, D G; Kavanagh, J J; Maxwell, G L; Bookman, M A

2018-02-01

To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. Published by Elsevier Inc.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study

PubMed Central

Hamilton, C. A.; Miller, A.; Casablanca, Y.; Horowitz, N. S.; Rungruang, B.; Krivak, T. C.; Richard, S. D.; Rodriguez, N.; Birrer, M.J.; Backes, F.J.; Geller, M.A.; Quinn, M.; Goodheart, M.J.; Mutch, D.G.; Kavanagh, J.J.; Maxwell, G. L.; Bookman, M. A.

2018-01-01

Objective To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Methods Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10 years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). Results The analysis dataset included 3,010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. Conclusions The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. PMID:29195926

The Risk of Developing Diabetes Mellitus in Patients with Psoriatic Arthritis: A Cohort Study.

PubMed

Eder, Lihi; Chandran, Vinod; Cook, Richard; Gladman, Dafna D

2017-03-01

To estimate the prevalence of diabetes mellitus (DM) in patients with psoriatic arthritis (PsA) in comparison with the general population and to assess whether the level of disease activity over time predicts the development of DM in these patients. A cohort analysis was conducted in patients followed in a large PsA clinic from 1978 to 2014. The prevalence of DM in the patients was compared with the general population of Ontario, Canada, and the age-standardized prevalence ratio (SPR) was calculated. For the assessment of risk factors for DM, time-weighted arithmetic mean (AM) levels of PsA-related disease activity measures were assessed as predictors for the development of DM. Multivariable Cox proportional hazards models were used to compute HR for incident DM after controlling for potential confounders. A total of 1305 patients were included in the analysis. The SPR of DM in PsA compared with the general population in Ontario was 1.43 (p = 0.002). Of the 1065 patients who were included in the time-to-event analysis, 73 patients were observed to develop DM. Based on multivariable analyses, AM tender joint count (HR 1.53, 95% CI 1.08-2.18, p = 0.02) and AM erythrocyte sedimentation rate (HR 1.21, 95% CI 1.03-1.41, p = 0.02) predicted the development of DM. The prevalence of DM is higher in patients with PsA compared with the general population. Patients with elevated levels of disease activity are at higher risk of developing DM.

Environmental Influences on Daily Emergency Admissions in Sickle-Cell Disease Patients

PubMed Central

Mekontso Dessap, Armand; Contou, Damien; Dandine-Roulland, Claire; Hemery, François; Habibi, Anoosha; Charles-Nelson, Anaïs; Galacteros, Frederic; Brun-Buisson, Christian; Maitre, Bernard; Katsahian, Sandrine

2014-01-01

Abstract Previous reports have suggested a role for weather conditions and air pollution on the variability of sickle cell disease (SCD) severity, but large-scale comprehensive epidemiological studies are lacking. In order to evaluate the influence of air pollution and climatic factors on emergency hospital admissions (EHA) in SCD patients, we conducted an 8-year observational retrospective study in 22 French university hospitals in Paris conurbation, using distributed lag non-linear models, a methodology able to flexibly describe simultaneously non-linear and delayed associations, with a multivariable approach. During the 2922 days of the study, there were 17,710 EHA, with a mean daily number of 6.1 ± 2.8. Most environmental factors were significantly correlated to each other. The risk of EHA was significantly associated with higher values of nitrogen dioxide, atmospheric particulate matters, and daily mean wind speed; and with lower values of carbon monoxide, ozone, sulfur dioxide, daily temperature (minimal, maximal, mean, and range), day-to-day mean temperature change, daily bright sunshine, and occurrence of storm. There was a lag effect for 12 of 15 environmental factors influencing hospitalization rate. Multivariate analysis identified carbon monoxide, day-to-day temperature change, and mean wind speed, along with calendar factors (weekend, summer season, and year) as independent factors associated with EHA. In conclusion, most weather conditions and air pollutants assessed were correlated to each other and influenced the rate of EHA in SCD patients. In multivariate analysis, lower carbon monoxide concentrations, day-to-day mean temperature drop and higher wind speed were associated with increased risk of EHA. PMID:25546672

Environmental influences on daily emergency admissions in sickle-cell disease patients.

PubMed

Mekontso Dessap, Armand; Contou, Damien; Dandine-Roulland, Claire; Hemery, François; Habibi, Anoosha; Charles-Nelson, Anaïs; Galacteros, Frederic; Brun-Buisson, Christian; Maitre, Bernard; Katsahian, Sandrine

2014-12-01

Previous reports have suggested a role for weather conditions and air pollution on the variability of sickle cell disease (SCD) severity, but large-scale comprehensive epidemiological studies are lacking. In order to evaluate the influence of air pollution and climatic factors on emergency hospital admissions (EHA) in SCD patients, we conducted an 8-year observational retrospective study in 22 French university hospitals in Paris conurbation, using distributed lag non-linear models, a methodology able to flexibly describe simultaneously non-linear and delayed associations, with a multivariable approach. During the 2922 days of the study, there were 17,710 EHA, with a mean daily number of 6.1 ± 2.8. Most environmental factors were significantly correlated to each other. The risk of EHA was significantly associated with higher values of nitrogen dioxide, atmospheric particulate matters, and daily mean wind speed; and with lower values of carbon monoxide, ozone, sulfur dioxide, daily temperature (minimal, maximal, mean, and range), day-to-day mean temperature change, daily bright sunshine, and occurrence of storm. There was a lag effect for 12 of 15 environmental factors influencing hospitalization rate. Multivariate analysis identified carbon monoxide, day-to-day temperature change, and mean wind speed, along with calendar factors (weekend, summer season, and year) as independent factors associated with EHA. In conclusion, most weather conditions and air pollutants assessed were correlated to each other and influenced the rate of EHA in SCD patients. In multivariate analysis, lower carbon monoxide concentrations, day-to-day mean temperature drop and higher wind speed were associated with increased risk of EHA.

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre.

PubMed

Gheorghe, Liana; Popescu, Irinel; Iacob, Speranta; Gheorghe, Cristian; Vaidan, Roxana; Constantinescu, Alexandra; Iacob, Razvan; Becheanu, Gabriel; Angelescu, Corina; Diculescu, Mircea

2004-09-01

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10. There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study

PubMed Central

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-01-01

Background This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). Material/Methods Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). Results The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. Conclusions The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients. PMID:28548078

Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

PubMed

Jeong, Anna; Wong, Michael

2016-09-01

Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p < 0.001), shagreen patches (OR 1.7, CI 1.0-2.7, p = 0.04), and facial angiofibromas (OR 1.7, CI 1.1-2.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort.

PubMed

Arroyo-Ávila, Mariangelí; Santiago-Casas, Yesenia; McGwin, Gerald; Cantor, Ryan S; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D; Kimberly, Robert P; Alarcón, Graciela S; Vilá, Luis M; Brown, Elizabeth E

2015-07-01

The aim of this study was to determine the association of anti-Sm antibodies with clinical manifestations, comorbidities, and disease damage in a large multi-ethnic SLE cohort. SLE patients (per American College of Rheumatology criteria), age ≥16 years, disease duration ≤10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal US cohort were studied. Socioeconomic-demographic features, cumulative clinical manifestations, comorbidities, and disease damage (as per the Systemic Lupus International Collaborating Clinics Damage Index [SDI]) were determined. The association of anti-Sm antibodies with clinical features was examined using multivariable logistic regression analyses adjusting for age, gender, ethnicity, disease duration, level of education, health insurance, and smoking. A total of 2322 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.4 (12.8) years and the mean (SD) disease duration was 9.0 (7.9) years; 2127 (91.6%) were women. Anti-Sm antibodies were present in 579 (24.9%) patients. In the multivariable analysis, anti-Sm antibodies were significantly associated with serositis, renal involvement, psychosis, vasculitis, Raynaud's phenomenon, hemolytic anemia, leukopenia, lymphopenia, and arterial hypertension. No significant association was found for damage accrual. In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis.

Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

PubMed

Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

2017-09-01

Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

Control-group feature normalization for multivariate pattern analysis of structural MRI data using the support vector machine.

PubMed

Linn, Kristin A; Gaonkar, Bilwaj; Satterthwaite, Theodore D; Doshi, Jimit; Davatzikos, Christos; Shinohara, Russell T

2016-05-15

Normalization of feature vector values is a common practice in machine learning. Generally, each feature value is standardized to the unit hypercube or by normalizing to zero mean and unit variance. Classification decisions based on support vector machines (SVMs) or by other methods are sensitive to the specific normalization used on the features. In the context of multivariate pattern analysis using neuroimaging data, standardization effectively up- and down-weights features based on their individual variability. Since the standard approach uses the entire data set to guide the normalization, it utilizes the total variability of these features. This total variation is inevitably dependent on the amount of marginal separation between groups. Thus, such a normalization may attenuate the separability of the data in high dimensional space. In this work we propose an alternate approach that uses an estimate of the control-group standard deviation to normalize features before training. We study our proposed approach in the context of group classification using structural MRI data. We show that control-based normalization leads to better reproducibility of estimated multivariate disease patterns and improves the classifier performance in many cases. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

PubMed

Jin, Zhaohui; Hartgers, Mindy L; Sanhueza, Cristobal T; Shubert, Christopher R; Alberts, Steven R; Truty, Mark J; Muppa, Prasuna; Nagorney, David M; Smyrk, Thomas C; Hassan, Mohamed; Mahipal, Amit

2018-05-01

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Association between rheumatic diseases and cancer: results from a clinical practice cohort study.

PubMed

Bellan, Mattia; Boggio, Enrico; Sola, Daniele; Gibbin, Antonello; Gualerzi, Alessandro; Favretto, Serena; Guaschino, Giulia; Bonometti, Ramona; Pedrazzoli, Roberta; Pirisi, Mario; Sainaghi, Pier Paolo

2017-08-01

The association between cancer and immune-mediated rheumatic conditions is controversial, especially as far as polymyalgia rheumatica (PMR) is concerned. Furthermore, no clinical feature has been shown to be suggestive of a paraneoplastic rheumatic syndrome. With the present study, we aim to address both these issues. The study population comprised N = 1750 patients, including N = 100 with PMR, who attended our tertiary immuno-rheumatology clinic between January 1, 2005 and November 30, 2012. A rheumatic disease was deemed paraneoplastic if cancer had been diagnosed in the 2 years preceding or following its onset. The probability of a significant association between a specific rheumatic disease and cancer was evaluated by computing the odds ratio (OR): N = 702 patients with osteoarthritis serving as controls. Furthermore, clinical features distinguishing paraneoplastic rheumatic diseases were searched for by univariate and multivariate analysis. Sjogren's syndrome (SS) [OR 3.6 (CI 95% 1.7-7.5)], PMR (OR 5.1 CI 95% 2.9-8.9), dermatomyositis/polymyositis [OR 12.09 (CI 95% 2.6-55.8)] and vasculitis [OR 3.70 (CI 95% 1.81-7.52)] are associated with cancer. At multivariate analysis, older age is associated with cancer among SS patients (p = 0.03), while in the PMR group, older age, male gender, and ≥6 tender joints are independent predictors of paraneoplastic PMR (p < 0.0004). Cancer frequently either heralds or follows rheumatic manifestations, including PMR. Older age, male gender and a more extensive joint involvement should be considered red flags for paraneoplastic PMR.

Multivariate Bayesian modeling of known and unknown causes of events--an application to biosurveillance.

PubMed

Shen, Yanna; Cooper, Gregory F

2012-09-01

This paper investigates Bayesian modeling of known and unknown causes of events in the context of disease-outbreak detection. We introduce a multivariate Bayesian approach that models multiple evidential features of every person in the population. This approach models and detects (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively non-informative prior probabilities. We report the results of simulation experiments which support that this modeling method can improve the detection of new disease outbreaks in a population. A contribution of this paper is that it introduces a multivariate Bayesian approach for jointly modeling both known and unknown causes of events. Such modeling has general applicability in domains where the space of known causes is incomplete. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Male circumcision, religion, and infectious diseases: an ecologic analysis of 118 developing countries

PubMed Central

Drain, Paul K; Halperin, Daniel T; Hughes, James P; Klausner, Jeffrey D; Bailey, Robert C

2006-01-01

Background Both religious practices and male circumcision (MC) have been associated with HIV and other sexually-transmitted infectious diseases. Most studies have been limited in size and have not adequately controlled for religion, so these relationships remain unclear. Methods We evaluated relationships between MC prevalence, Muslim and Christian religion, and 7 infectious diseases using country-specific data among 118 developing countries. We used multivariate linear regression to describe associations between MC and cervical cancer incidence, and between MC and HIV prevalence among countries with primarily sexual HIV transmission. Results Fifty-three, 14, and 51 developing countries had a high (>80%), intermediate (20–80%), and low (<20%) MC prevalence, respectively. In univariate analyses, MC was associated with lower HIV prevalence and lower cervical cancer incidence, but not with HSV-2, syphilis, nor, as expected, with Hepatitis C, tuberculosis, or malaria. In multivariate analysis after stratifying the countries by religious groups, each categorical increase of MC prevalence was associated with a 3.65/100,000 women (95% CI 0.54-6.76, p = 0.02) decrease in annual cervical cancer incidence, and a 1.84-fold (95% CI 1.36-2.48, p < 0.001) decrease in the adult HIV prevalence among sub-Saharan African countries. In separate multivariate analyses among non-sub-Saharan African countries controlling for religion, higher MC prevalence was associated with a 8.94-fold (95% CI 4.30-18.60) decrease in the adult HIV prevalence among countries with primarily heterosexual HIV transmission, but not, as expected, among countries with primarily homosexual or injection drug use HIV transmission (p = 0.35). Conclusion Male circumcision was significantly associated with lower cervical cancer incidence and lower HIV prevalence in sub-Saharan Africa, independent of Muslim and Christian religion. As predicted, male circumcision was also strongly associated with lower HIV prevalence among countries with primarily heterosexual HIV transmission, but not among countries with primarily homosexual or injection drug use HIV transmission. These findings strengthen the reported biological link between MC and some sexually transmitted infectious diseases, including HIV and cervical cancer. PMID:17137513

TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing vasculature?

PubMed

Kwok, C S; Ong, A C L; Potter, J F; Metcalf, A K; Myint, P K

2014-06-01

We sought to identify the determinants of orthostatic hypotension (OH) among patients referred to the transient ischaemic attack (TIA) clinic. We conducted a retrospective analysis of prospectively collected data on patients who attended the TIA clinic in a UK hospital between January 2006 and September 2009. Each patient had their supine and standing or sitting blood pressure measured. Logistic regression was used to estimate the univariate and multivariate odds of OH for the subgroups of patients based on their diagnosis. A 10% significance level for the univariate analysis was used to identify variables in the multivariate model. A total of 3222 patients were studied of whom 1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of either systolic or diastolic OH in the TIA, stroke and patients with other diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292), respectively. Multivariate analyses showed age, prior history of TIA, and diabetes were independently significantly associated with systolic OH alone or diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56 (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the diagnosis of stroke, peripheral vascular disease (PVD) was significantly associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a significantly lower odds of OH (0.61, 0.42-0.88). In patients with other diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH. Orthostatic hypotension is prevalent among patients presenting to TIA clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be a significant associate of OH in this patient population. © 2014 John Wiley & Sons Ltd.

Small Bowel Carcinomas in Coeliac or Crohn's Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium.

PubMed

Vanoli, Alessandro; Di Sabatino, Antonio; Furlan, Daniela; Klersy, Catherine; Grillo, Federica; Fiocca, Roberto; Mescoli, Claudia; Rugge, Massimo; Nesi, Gabriella; Fociani, Paolo; Sampietro, Gianluca; Ardizzone, Sandro; Luinetti, Ombretta; Calabrò, Antonio; Tonelli, Francesco; Volta, Umberto; Santini, Donatella; Caio, Giacomo; Giuffrida, Paolo; Elli, Luca; Ferrero, Stefano; Latella, Giovanni; Ciardi, Antonio; Caronna, Roberto; Solina, Gaspare; Rizzo, Aroldo; Ciacci, Carolina; D'Armiento, Francesco P; Salemme, Marianna; Villanacci, Vincenzo; Cannizzaro, Renato; Canzonieri, Vincenzo; Reggiani Bonetti, Luca; Biancone, Livia; Monteleone, Giovanni; Orlandi, Augusto; Santeusanio, Giuseppe; Macciomei, Maria C; D'Incà, Renata; Perfetti, Vittorio; Sandri, Giancarlo; Silano, Marco; Florena, Ada M; Giannone, Antonino G; Papi, Claudio; Coppola, Luigi; Usai, Paolo; Maccioni, Antonio; Astegiano, Marco; Migliora, Paola; Manca, Rachele; Martino, Michele; Trapani, Davide; Cerutti, Roberta; Alberizzi, Paola; Riboni, Roberta; Sessa, Fausto; Paulli, Marco; Solcia, Enrico; Corazza, Gino R

2017-08-01

An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

The association between socioeconomic status and the symptoms at diagnosis of celiac disease: a retrospective cohort study.

PubMed

Roy, Abhik; Mehra, Shilpa; Kelly, Ciarán P; Tariq, Sohaib; Pallav, Kumar; Dennis, Melinda; Peer, Ann; Lebwohl, Benjamin; Green, Peter H R; Leffler, Daniel A

2016-07-01

There are little data on patient factors that impact diagnosis rates of celiac disease. This study aims to evaluate the association between patient socioeconomic status and the symptoms at diagnosis of celiac disease. A total of 872 patients with biopsy-proven celiac disease were categorized based on the presence or absence of (1) diarrhea and (2) any gastrointestinal symptoms at diagnosis. Univariate and multivariate analyses were used to assess the association between socioeconomic status and symptoms. Patients without diarrhea at presentation had a higher mean per capita income (US$34,469 versus US$32,237, p = 0.02), and patients without any gastrointestinal symptoms had a higher mean per capita income (US$36,738 versus US$31,758, p < 0.01) compared with patients having such symptoms. On multivariable analysis adjusting for sex, age, autoimmune or psychiatric comorbidities, and income, per capita income remained a significant predictor of diagnosis without gastrointestinal symptoms (odds ratio: 1.71, 95% confidence interval: 1.17-2.50, p < 0.01), and it showed a trend towards significance in diagnosis without diarrhea (odds ratio: 1.40, 95% confidence interval: 0.98-2.02, p = 0.06). Patients with nonclassical symptoms of celiac disease are less likely to be diagnosed if they are of lower socioeconomic status. Celiac disease may be under-recognized in this population due to socioeconomic factors that possibly include lower rates of health-seeking behavior and access to healthcare.

Association of Discoid Lupus with Clinical Manifestations and Damage Accrual in PROFILE: A Multiethnic Lupus Cohort

PubMed Central

Santiago-Casas, Yesenia; Vilá, Luis M.; McGwin, Gerald; Cantor, Ryan S.; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.

2013-01-01

Objective To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort. Methods SLE patients (per ACR criteria), age ≥ 16 years, disease duration ≤ 10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations and disease damage [as per the Systemic Lupus International Collaborating Clinics Damage Index (SDI)] were determined. The association of DLE with clinical manifestations and disease damage was examined using multivariable logistic regression. Results A total of 2,228 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.3 (12.8) years and the mean (SD) disease duration was 7.9 (6.0) years; 91.8% were women. Discoid lupus was observed in 393 (17.6%) of patients with SLE. In the multivariable analysis, patients with discoid lupus were more likely to be smokers and of African-American ethnicity, and to have malar rash, photosensitivity, oral ulcers, leukopenia and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity, and to have arthritis, end-stage renal disease (ESRD), and antinuclear, anti-dsDNA and anti-phospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers. Conclusion In this cohort of SLE patients, discoid lupus was associated with several clinical features including serious manifestations such as vasculitis and chronic seizures. PMID:22190480

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sole, Claudio V., E-mail: csole@iram.cl; School of Medicine, Complutense University, Madrid; Calvo, Felipe A.

Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-freemore » survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.« less

pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karam, Irene; Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC; Lesperance, Maria F.

Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examinedmore » outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal locoregional management for women with pN0(i+) breast cancer.« less

Determinants of elevated healthcare utilization in patients with COPD.

PubMed

Simon-Tuval, Tzahit; Scharf, Steven M; Maimon, Nimrod; Bernhard-Scharf, Barbara J; Reuveni, Haim; Tarasiuk, Ariel

2011-01-13

Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems. Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system. Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency. Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database. Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients. Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001). The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs. Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01-1.2), history of: myocardial infarct (2.87; 1.5-5.5), congestive heart failure (3.52; 1.9-6.4), mild liver disease (3.83; 1.3-11.2) and diabetes (2.02; 1.1-3.6). Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis. Comorbidity burden determines elevated utilization for COPD patients. Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

PubMed

Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

2016-01-15

The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk models for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP): smoking and chronic liver disease are predictors of protection against PEP.

PubMed

DiMagno, Matthew J; Spaete, Joshua P; Ballard, Darren D; Wamsteker, Erik-Jan; Saini, Sameer D

2013-08-01

We investigated which variables independently associated with protection against or development of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and severity of PEP. Subsequently, we derived predictive risk models for PEP. In a case-control design, 6505 patients had 8264 ERCPs, 211 patients had PEP, and 22 patients had severe PEP. We randomly selected 348 non-PEP controls. We examined 7 established- and 9 investigational variables. In univariate analysis, 7 variables predicted PEP: younger age, female sex, suspected sphincter of Oddi dysfunction (SOD), pancreatic sphincterotomy, moderate-difficult cannulation (MDC), pancreatic stent placement, and lower Charlson score. Protective variables were current smoking, former drinking, diabetes, and chronic liver disease (CLD, biliary/transplant complications). Multivariate analysis identified seven independent variables for PEP, three protective (current smoking, CLD-biliary, CLD-transplant/hepatectomy complications) and 4 predictive (younger age, suspected SOD, pancreatic sphincterotomy, MDC). Pre- and post-ERCP risk models of 7 variables have a C-statistic of 0.74. Removing age (seventh variable) did not significantly affect the predictive value (C-statistic of 0.73) and reduced model complexity. Severity of PEP did not associate with any variables by multivariate analysis. By using the newly identified protective variables with 3 predictive variables, we derived 2 risk models with a higher predictive value for PEP compared to prior studies.

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study.

PubMed

Duruisseaux, Michaël; Besse, Benjamin; Cadranel, Jacques; Pérol, Maurice; Mennecier, Bertrand; Bigay-Game, Laurence; Descourt, Renaud; Dansin, Eric; Audigier-Valette, Clarisse; Moreau, Lionel; Hureaux, José; Veillon, Remi; Otto, Josiane; Madroszyk-Flandin, Anne; Cortot, Alexis; Guichard, François; Boudou-Rouquette, Pascaline; Langlais, Alexandra; Missy, Pascale; Morin, Franck; Moro-Sibilot, Denis

2017-03-28

Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

Periodontal inflamed surface area as a novel numerical variable describing periodontal conditions

PubMed Central

2017-01-01

Purpose A novel index, the periodontal inflamed surface area (PISA), represents the sum of the periodontal pocket depth of bleeding on probing (BOP)-positive sites. In the present study, we evaluated correlations between PISA and periodontal classifications, and examined PISA as an index integrating the discrete conventional periodontal indexes. Methods This study was a cross-sectional subgroup analysis of data from a prospective cohort study investigating the association between chronic periodontitis and the clinical features of ankylosing spondylitis. Data from 84 patients without systemic diseases (the control group in the previous study) were analyzed in the present study. Results PISA values were positively correlated with conventional periodontal classifications (Spearman correlation coefficient=0.52; P<0.01) and with periodontal indexes, such as BOP and the plaque index (PI) (r=0.94; P<0.01 and r=0.60; P<0.01, respectively; Pearson correlation test). Porphyromonas gingivalis (P. gingivalis) expression and the presence of serum P. gingivalis antibodies were significant factors affecting PISA values in a simple linear regression analysis, together with periodontal classification, PI, bleeding index, and smoking, but not in the multivariate analysis. In the multivariate linear regression analysis, PISA values were positively correlated with the quantity of current smoking, PI, and severity of periodontal disease. Conclusions PISA integrates multiple periodontal indexes, such as probing pocket depth, BOP, and PI into a numerical variable. PISA is advantageous for quantifying periodontal inflammation and plaque accumulation. PMID:29093989

Risk factors for superficial surgical site infection after elective rectal cancer resection: a multivariate analysis of 8880 patients from the American College of Surgeons National Surgical Quality Improvement Program database.

PubMed

Sutton, Elie; Miyagaki, Hiromichi; Bellini, Geoffrey; Shantha Kumara, H M C; Yan, Xiaohong; Howe, Brett; Feigel, Amanda; Whelan, Richard L

2017-01-01

Superficial surgical site infection (sSSI) is one of the most common complications after colorectal resection. The goal of this study was to determine the comorbidities and operative characteristics that place patients at risk for sSSI in patients who underwent rectal cancer resection. The American College of Surgeons National Surgical Quality Improvement Program database was queried (via diagnosis and Current Procedural Terminology codes) for patients with rectal cancer who underwent elective resection between 2005 and 2012. Patients for whom data concerning 27 demographic factors, comorbidities, and operative characteristics were available were eligible. A univariate and multivariate analysis was performed to identify possible risk factors for sSSI. A total of 8880 patients met the entry criteria and were included. sSSIs were diagnosed in 861 (9.7%) patients. Univariate analysis found 14 patients statistically significant risk factors for sSSI. Multivariate analysis revealed the following risk factors: male gender, body mass index (BMI) >30, current smoking, history of chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists III/IV, abdominoperineal resection (APR), stoma formation, open surgery (versus laparoscopic), and operative time >217 min. The greatest difference in sSSI rates was noted in patients with COPD (18.9 versus 9.5%). Of note, 54.2% of sSSIs was noted after hospital discharge. With regard to the timing of presentation, univariate analysis revealed a statistically significant delay in sSSI presentation in patients with the following factors and/or characteristics: BMI <30, previous radiation therapy (RT), APR, minimally invasive surgery, and stoma formation. Multivariate analysis suggested that only laparoscopic surgery (versus open) and preoperative RT were risk factors for delay. Rectal cancer resections are associated with a high incidence of sSSIs, over half of which are noted after discharge. Nine patient and operative characteristics, including smoking, BMI, COPD, APR, and open surgery were found to be significant risk factors for SSI on multivariate analysis. Furthermore, sSSI presentation in patients who had laparoscopic surgery and those who had preoperative RT is significantly delayed for unclear reasons. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Takenaka, Daisuke; Kaminaga, Shigeo; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2018-02-01

The objective of this study was to compare the capability of xenon-enhanced area-detector CT (ADCT) performed with a subtraction technique and coregistered 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity in smokers. Forty-six consecutive smokers (32 men and 14 women; mean age, 67.0 years) underwent prospective unenhanced and xenon-enhanced ADCT, 81m Kr-ventilation SPECT/CT, and pulmonary function tests. Disease severity was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. CT-based functional lung volume (FLV), the percentage of wall area to total airway area (WA%), and ventilated FLV on xenon-enhanced ADCT and SPECT/CT were calculated for each smoker. All indexes were correlated with percentage of forced expiratory volume in 1 second (%FEV 1 ) using step-wise regression analyses, and univariate and multivariate logistic regression analyses were performed. In addition, the diagnostic accuracy of the proposed model was compared with that of each radiologic index by means of McNemar analysis. Multivariate logistic regression showed that %FEV 1 was significantly affected (r = 0.77, r 2 = 0.59) by two factors: the first factor, ventilated FLV on xenon-enhanced ADCT (p < 0.0001); and the second factor, WA% (p = 0.004). Univariate logistic regression analyses indicated that all indexes significantly affected GOLD classification (p < 0.05). Multivariate logistic regression analyses revealed that ventilated FLV on xenon-enhanced ADCT and CT-based FLV significantly influenced GOLD classification (p < 0.0001). The diagnostic accuracy of the proposed model was significantly higher than that of ventilated FLV on SPECT/CT (p = 0.03) and WA% (p = 0.008). Xenon-enhanced ADCT is more effective than 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity.

Analysis of a Single Hemodialysis on Phosphate Removal of the Internal Fistula Patients by Mathematical and Statistical Methods

PubMed Central

Yu, Qiyao; Bai, Yaling; Zhang, Junxia; Cui, Liwen; Zhang, Huiran; Xu, Jinsheng; Gao, Chao

2013-01-01

Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide challenge in hemodialysis patients. In china, the number of dialysis patients is growing but few data are available about their bone disorders. In the current study, we aimed to evaluate the effect of clinical factors on the serum phosphorus clearance in the 80 maintenance hemodialysis (MHD) patients. Six clinical factors were identified for their association with the serum phosphorus clearance using the analysis of Spearman's single linear correlation, including predialysis serum phosphate level, CRR, membrane surface area of the dialyzer, effective blood flow rate, the blood chamber volume, and hematocrit. In an overall multivariate analysis, pre-P, CRR, membrane SA, and Qb were identified as independent risk factors associated with the serum phosphorus clearance. In conclusion, HD could effectively clear serum phosphorus. The analysis of CRR might help to estimate serum phosphorus reduction ratio. PMID:24454542

Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis.

PubMed

Proitsi, Petroula; Kim, Min; Whiley, Luke; Simmons, Andrew; Sattlecker, Martina; Velayudhan, Latha; Lupton, Michelle K; Soininen, Hillka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Powell, John F; Dobson, Richard J B; Legido-Quigley, Cristina

2017-02-01

The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex). We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods. We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R 2  = 0.10, test data set) and brain atrophy (R 2  ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines. Blood lipids are promising AD biomarkers that may lead to new treatment strategies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Multivariate analysis in thoracic research.

PubMed

Mengual-Macenlle, Noemí; Marcos, Pedro J; Golpe, Rafael; González-Rivas, Diego

2015-03-01

Multivariate analysis is based in observation and analysis of more than one statistical outcome variable at a time. In design and analysis, the technique is used to perform trade studies across multiple dimensions while taking into account the effects of all variables on the responses of interest. The development of multivariate methods emerged to analyze large databases and increasingly complex data. Since the best way to represent the knowledge of reality is the modeling, we should use multivariate statistical methods. Multivariate methods are designed to simultaneously analyze data sets, i.e., the analysis of different variables for each person or object studied. Keep in mind at all times that all variables must be treated accurately reflect the reality of the problem addressed. There are different types of multivariate analysis and each one should be employed according to the type of variables to analyze: dependent, interdependence and structural methods. In conclusion, multivariate methods are ideal for the analysis of large data sets and to find the cause and effect relationships between variables; there is a wide range of analysis types that we can use.

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

PubMed

Shen, Shutong; Gao, Rongrong; Bei, Yihua; Li, Jin; Zhang, Haifeng; Zhou, Yanli; Yao, Wenming; Xu, Dongjie; Zhou, Fang; Jin, Mengchao; Wei, Siqi; Wang, Kai; Xu, Xuejuan; Li, Yongqin; Xiao, Junjie; Li, Xinli

2017-01-01

Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed. © 2017 The Author(s). Published by S. Karger AG, Basel.

Meta-analysis of gene-level associations for rare variants based on single-variant statistics.

PubMed

Hu, Yi-Juan; Berndt, Sonja I; Gustafsson, Stefan; Ganna, Andrea; Hirschhorn, Joel; North, Kari E; Ingelsson, Erik; Lin, Dan-Yu

2013-08-08

Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Factors associated with disease expression patterns in systemic lupus erythematosus patients: results from LUMINA (LXXVII), a multiethnic US cohort.

PubMed

Ugarte-Gil, M F; Pimentel-Quiroz, V R; Vilá, L M; Reveille, J D; McGwin, G; Alarcón, G S

2017-05-01

Objective The objective of this study was to determine the association of disease expression patterns with demographic and clinical characteristics in SLE. Methods Patients from a multi-ethnic SLE cohort were included. Disease expression patterns were defined as acute SLE and insidious SLE; this group was divided into those who accrued three ACR criteria and then accrued the fourth (insidious pattern A) and those who have one or two and then accrued four criteria (insidious pattern B). Disease activity was ascertained with the SLAM-R and disease damage with SLICC/ACR damage index. Variables were compared using analysis of variance for numeric variables and χ 2 for categorical variables. Multivariable analyses adjusting for possible confounders were performed. Results Six hundred and forty patients were included; the most frequent pattern was the insidious pattern B, with 415 (64.8%) patients, followed by the acute SLE group with 115 (18.0%) and the insidious pattern A with 110 (17.2%) patients. Patients from the insidious pattern A were older at diagnosis (pattern A: 39.8 vs pattern B: 36.7 vs acute: 32.4 years; p < 0.0001), more educated (13.6 vs 13.1 vs 12.1; p = 0.0008) and with a less active disease at baseline (8.8 vs 9.2 vs 10.7; p = 0.0227). Caucasian and Hispanic (Puerto Rico) ethnicities were overrepresented in this group (40.0% vs 27.7% vs 19.1% and 18.2% vs 17.1% vs 9.6%; p = 0.0003). Conclusions More insidious onset is associated with older age, Caucasian ethnicity, higher level of education, and lower disease activity than those with acute onset. However, after multivariable analyses, disease activity was not associated with any disease expression pattern.

Clinical and serologic factors associated with lupus pleuritis.

PubMed

Mittoo, Shikha; Gelber, Allan C; Hitchon, Carol A; Silverman, Earl D; Pope, Janet E; Fortin, Paul R; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Gladman, Dafna D; Urowitz, Murray B; Zummer, Michel; Clarke, Ann E; Bernatsky, Sasha; Hudson, Marie; Tucker, Lori B; Petty, Ross E; Peschken, Christine A

2010-04-01

Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort. We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression. In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (+/- SD) was 46.8 +/- 13.5 years, and disease duration at study entry was 12.1 +/- 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p

[Association between adverse experiences in childhood and risk of chronic diseases in adulthood].

PubMed

Nie, Junyan; Yu, Honghui; Wang, Zhiqiang; Wang, Leilei; Han, Juan; Wang, Youjie; Du, Yukai; Shen, Min

2015-09-01

To analyze the prevalence and characteristics of childhood adverse experiences among adults aged 18-59 years and understand the association between childhood adverse experiences and risk of chronic diseases in adulthood. A cross-sectional study was conducted with a questionnaire among adults aged 18-59 years selected through cluster random sampling from 3 communities in Macheng, Hubei province. Uinivariate and multivariate logistic regression analyses were conducted to evaluate the association between adverse experiences in childhood and the risk of chronic diseases in adulthood. A total of 1 767 adults aged 18-59 years were surveyed and 1 501 valid questionnaires were returned. The average age was (36.32± 10.20) years for males and (35.72±9.08) years for females. The prevalence rate of childhood adverse experiences was 66.22%. The risk of chronic disease in adults increased with the increase of the score indicating childhood adverse experiences (Z=-5.902 1, P<0.000 1). Multivariate logistic regression analysis showed that being physically abused (OR=1.93, 95% CI: 1.41-2.64), substance abuse in family (OR=2.82, 95% CI: 1.16-6.80), being bullied (OR=2.59, 95% CI: 1.39-4.80) and parents separation/divorce (OR=1.51, 95% CI: 1.09-2.09) were significantly associated with risk of chronic diseases in adulthood. The prevalence of adverse childhood experiences was high in adults aged 18-59 years, which was significantly associated with the risk of chronic diseases in adulthood. Early prevention of chronic diseases should be conducted in childhood.

Association between hepatitis C infection and cerebro-cardiovascular disease: analysis of a national population-based survey in Egypt.

PubMed

Gadallah, Mohsen; Kandil, Sahar; Mohsen, Amira

2018-05-03

To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro-cardiovascular (CCV) disease. The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25-59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV-RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27-2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23-1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62-4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV-positive reactors for preventive and curative programmes addressing extrahepatic complications. © 2018 John Wiley & Sons Ltd.

Designing a risk-based surveillance program for Mycobacterium avium ssp. paratuberculosis in Norwegian dairy herds using multivariate statistical process control analysis.

PubMed

Whist, A C; Liland, K H; Jonsson, M E; Sæbø, S; Sviland, S; Østerås, O; Norström, M; Hopp, P

2014-11-01

Surveillance programs for animal diseases are critical to early disease detection and risk estimation and to documenting a population's disease status at a given time. The aim of this study was to describe a risk-based surveillance program for detecting Mycobacterium avium ssp. paratuberculosis (MAP) infection in Norwegian dairy cattle. The included risk factors for detecting MAP were purchase of cattle, combined cattle and goat farming, and location of the cattle farm in counties containing goats with MAP. The risk indicators included production data [culling of animals >3 yr of age, carcass conformation of animals >3 yr of age, milk production decrease in older lactating cows (lactations 3, 4, and 5)], and clinical data (diarrhea, enteritis, or both, in animals >3 yr of age). Except for combined cattle and goat farming and cattle farm location, all data were collected at the cow level and summarized at the herd level. Predefined risk factors and risk indicators were extracted from different national databases and combined in a multivariate statistical process control to obtain a risk assessment for each herd. The ordinary Hotelling's T(2) statistic was applied as a multivariate, standardized measure of difference between the current observed state and the average state of the risk factors for a given herd. To make the analysis more robust and adapt it to the slowly developing nature of MAP, monthly risk calculations were based on data accumulated during a 24-mo period. Monitoring of these variables was performed to identify outliers that may indicate deviance in one or more of the underlying processes. The highest-ranked herds were scattered all over Norway and clustered in high-density dairy cattle farm areas. The resulting rankings of herds are being used in the national surveillance program for MAP in 2014 to increase the sensitivity of the ongoing surveillance program in which 5 fecal samples for bacteriological examination are collected from 25 dairy herds. The use of multivariate statistical process control for selection of herds will be beneficial when a diagnostic test suitable for mass screening is available and validated on the Norwegian cattle population, thus making it possible to increase the number of sampled herds. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Detection of Motor Impairment in Parkinson's Disease Via Mobile Touchscreen Typing.

PubMed

Arroyo-Gallego, Teresa; Ledesma-Carbayo, Maria Jesus; Sanchez-Ferro, Alvaro; Butterworth, Ian; Mendoza, Carlos S; Matarazzo, Michele; Montero, Paloma; Lopez-Blanco, Roberto; Puertas-Martin, Veronica; Trincado, Rocio; Giancardo, Luca

2017-09-01

Mobile technology is opening a wide range of opportunities for transforming the standard of care for chronic disorders. Using smartphones as tools for longitudinally tracking symptoms could enable personalization of drug regimens and improve patient monitoring. Parkinson's disease (PD) is an ideal candidate for these tools. At present, evaluation of PD signs requires trained experts to quantify motor impairment in the clinic, limiting the frequency and quality of the information available for understanding the status and progression of the disease. Mobile technology can help clinical decision making by completing the information of motor status between hospital visits. This paper presents an algorithm to detect PD by analyzing the typing activity on smartphones independently of the content of the typed text. We propose a set of touchscreen typing features based on a covariance, skewness, and kurtosis analysis of the timing information of the data to capture PD motor signs. We tested these features, both independently and in a multivariate framework, in a population of 21 PD and 23 control subjects, achieving a sensitivity/specificity of 0.81/0.81 for the best performing feature and 0.73/0.84 for the best multivariate method. The results of the alternating finger-tapping, an established motor test, measured in our cohort are 0.75/0.78. This paper contributes to the development of a home-based, high-compliance, and high-frequency PD motor test by analysis of routine typing on touchscreens.

[Chronic kidney disease in 5 708 people receiving physical examination].

PubMed

Xu, Guo; Chen, Zhiheng; Zhang, Hao; Gong, Ni; Wang, Yan

2014-04-01

To investigate chronic kidney disease (CKD) and its risk factors in people receiving physical examination. This retrospective study included people over 20 years old who had physical examination in the Health Management Center of Third Xiangya Hospital from Janurary 2008 to June 2011. CKD and its risk factors as well as questionnaire were recorded. The risk factors were analyzed by multivariate logistic analysis. CKD was defined by kidney damage (microalbuminuria≥30 mg/L) and/or hematuria and/or reduced kidney function [evaluate glomerular filtration rate (eGFR)<60 mL/(min.1.73 m2)]. We counted eGFR according to the modification of diet in renal disease (MDRD). A total of 5 708 physical examination reports were included. The detection rate of albuminuria, reduced renal function and hematuria was 25.0%, 1.7% and 1.1%. The detection rate of CKD was 25.6%, and detection rate of CKD stage 1-5 was 17.8%, 6.7%, 1.1%, 0 and 0, respectively. Multivariate logistic analysis indicated that diabetes mellitus, hypertension, hypercholesterolemia, male, age, and smoking were the risk factors for CKD. Increasing physical activity was the protective factor against CKD. High prevalence of CKD in people receiving physical examination is found in Changsha, especially stage 1 and 2 CKD. Physical examination is important to screen CKD. Stopping smoking, control of blood glucose, blood pressure, blood lipids and increasing physical activity may help reduce the prevalence of CKD.

Shifting chronic disease management from hospitals to primary care in Estonian health system: analysis of national panel data.

PubMed

Atun, Rifat; Gurol-Urganci, Ipek; Hone, Thomas; Pell, Lisa; Stokes, Jonathan; Habicht, Triin; Lukka, Kaija; Raaper, Elin; Habicht, Jarno

2016-12-01

Following independence from the Soviet Union in 1991, Estonia introduced a national insurance system, consolidated the number of health care providers, and introduced family medicine centred primary health care (PHC) to strengthen the health system. Using routinely collected health billing records for 2005-2012, we examine health system utilisation for seven ambulatory care sensitive conditions (ACSCs) (asthma, chronic obstructive pulmonary disease [COPD], depression, Type 2 diabetes, heart failure, hypertension, and ischemic heart disease [IHD]), and by patient characteristics (gender, age, and number of co-morbidities). The data set contained 552 822 individuals. We use patient level data to test the significance of trends, and employ multivariate regression analysis to evaluate the probability of inpatient admission while controlling for patient characteristics, health system supply-side variables, and PHC use. Over the study period, utilisation of PHC increased, whilst inpatient admissions fell. Service mix in PHC changed with increases in phone, email, nurse, and follow-up (vs initial) consultations. Healthcare utilisation for diabetes, depression, IHD and hypertension shifted to PHC, whilst for COPD, heart failure and asthma utilisation in outpatient and inpatient settings increased. Multivariate regression indicates higher probability of inpatient admission for males, older patient and especially those with multimorbidity, but protective effect for PHC, with significantly lower hospital admission for those utilising PHC services. Our findings suggest health system reforms in Estonia have influenced the shift of ACSCs from secondary to primary care, with PHC having a protective effect in reducing hospital admissions.

Risk Factors for Venous Thromboembolism in Chronic Obstructive Pulmonary Disease

PubMed Central

Kim, Victor; Goel, Nishant; Gangar, Jinal; Zhao, Huaqing; Ciccolella, David E.; Silverman, Edwin K.; Crapo, James D.; Criner, Gerard J.

2014-01-01

Background: COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear. Methods: Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology (COPDGene) study were divided into 2 groups: VTE+, those who reported a history of VTE by questionnaire, and VTE-, those who did not. We compared variables in these 2 groups with either t-test or chi-squared test for continuous and categorical variables, respectively. We performed a univariate logistic regression for VTE, and then a multivariate logistic regression using the significant predictors of interest in the univariate analysis to ascertain the determinants of VTE. Results: The VTE+ group was older, more likely to be Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had a lower 6-minute walk distance, worse quality of life scores, and more dyspnea and respiratory exacerbations than the VTE- group. Lung function was not different between groups. A greater percentage of the VTE+ group described multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk distance, pneumothorax, peripheral vascular disease, and congestive heart failure significantly increased the odds for VTE by history. Conclusions: BMI, exercise capacity, and medical comorbidities were significantly associated with VTE in moderate to severe COPD. Clinicians should suspect VTE in patients who present with dyspnea and should consider possibilities other than infection as causes of COPD exacerbation. PMID:25844397

Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

PubMed

Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

2015-07-02

Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease. © 2015 by The American Society of Hematology.

Medial prefrontal aberrations in major depressive disorder revealed by cytoarchitectonically informed voxel-based morphometry

PubMed Central

Bludau, Sebastian; Bzdok, Danilo; Gruber, Oliver; Kohn, Nils; Riedl, Valentin; Sorg, Christian; Palomero-Gallagher, Nicola; Müller, Veronika I.; Hoffstaedter, Felix; Amunts, Katrin; Eickhoff, Simon B.

2017-01-01

Objective The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The present study performs morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and controls using both uni- and multivariate statistics. Methods Multi-site voxel- and region-based morphometric MRI analysis of 73 depressed patients and 73 matched controls without psychiatric history. Frontal pole volume was first compared between depressed patients and controls by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. Results Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients. Conclusions Across disparate methods, we demonstrated subregion specificity in the left medial frontal pole volume in depressed patients. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology like the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression. PMID:26621569

Correlative and multivariate analysis of increased radon concentration in underground laboratory.

PubMed

Maletić, Dimitrije M; Udovičić, Vladimir I; Banjanac, Radomir M; Joković, Dejan R; Dragić, Aleksandar L; Veselinović, Nikola B; Filipović, Jelena

2014-11-01

The results of analysis using correlative and multivariate methods, as developed for data analysis in high-energy physics and implemented in the Toolkit for Multivariate Analysis software package, of the relations of the variation of increased radon concentration with climate variables in shallow underground laboratory is presented. Multivariate regression analysis identified a number of multivariate methods which can give a good evaluation of increased radon concentrations based on climate variables. The use of the multivariate regression methods will enable the investigation of the relations of specific climate variable with increased radon concentrations by analysis of regression methods resulting in 'mapped' underlying functional behaviour of radon concentrations depending on a wide spectrum of climate variables. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Multivariate Genome-Wide Association Analysis of 10 LDL Subfractions, and Their Response to Statin Treatment, in 1868 Caucasians

PubMed Central

Shim, Heejung; Chasman, Daniel I.; Smith, Joshua D.; Mora, Samia; Ridker, Paul M.; Nickerson, Deborah A.; Krauss, Ronald M.; Stephens, Matthew

2015-01-01

We conducted a genome-wide association analysis of 7 subfractions of low density lipoproteins (LDLs) and 3 subfractions of intermediate density lipoproteins (IDLs) measured by gradient gel electrophoresis, and their response to statin treatment, in 1868 individuals of European ancestry from the Pharmacogenomics and Risk of Cardiovascular Disease study. Our analyses identified four previously-implicated loci (SORT1, APOE, LPA, and CETP) as containing variants that are very strongly associated with lipoprotein subfractions (log10Bayes Factor > 15). Subsequent conditional analyses suggest that three of these (APOE, LPA and CETP) likely harbor multiple independently associated SNPs. Further, while different variants typically showed different characteristic patterns of association with combinations of subfractions, the two SNPs in CETP show strikingly similar patterns - both in our original data and in a replication cohort - consistent with a common underlying molecular mechanism. Notably, the CETP variants are very strongly associated with LDL subfractions, despite showing no association with total LDLs in our study, illustrating the potential value of the more detailed phenotypic measurements. In contrast with these strong subfraction associations, genetic association analysis of subfraction response to statins showed much weaker signals (none exceeding log10Bayes Factor of 6). However, two SNPs (in APOE and LPA) previously-reported to be associated with LDL statin response do show some modest evidence for association in our data, and the subfraction response proles at the LPA SNP are consistent with the LPA association, with response likely being due primarily to resistance of Lp(a) particles to statin therapy. An additional important feature of our analysis is that, unlike most previous analyses of multiple related phenotypes, we analyzed the subfractions jointly, rather than one at a time. Comparisons of our multivariate analyses with standard univariate analyses demonstrate that multivariate analyses can substantially increase power to detect associations. Software implementing our multivariate analysis methods is available at http://stephenslab.uchicago.edu/software.html. PMID:25898129

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, Abhinav V.; Pariser, Joseph J.; Pearce, Shane M.

2016-04-01

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined usingmore » follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.« less

[Investigation and analysis of factors that affect the health of children in the plastic recycling and regeneration processing region].

PubMed

Wang, Juanli; Li, Liping; Lu, Yaogui

2014-09-01

To investigate the main influential factors for the health of children in the plastic waste recovery and recycling area. A cross-sectional survey was performed among children aged 9∼17 years from three natural villages engaged in plastic waste recovery and recycling and four control villages engaged in planting. The health status of children was investigated by random household survey using a face-to-face questionnaire, and the main influential factors were analyzed accordingly. The incidence rates of respiratory symptoms (cough and expectoration, nasal congestion, and sore throat) (78.4%, 69/88) and digestive diseases (gastrointestinal disease and liver disease) (14.8%, 13/88) in the waste processing area were significantly higher than those in the control area (64.0%, 71/111; 6.3%, 7/111) (P < 0.05). Multivariate logistic regression analysis indicated that skin diseases are related to whether plastic can be smelt around the residential area.

Estimation and Psychometric Analysis of Component Profile Scores via Multivariate Generalizability Theory

ERIC Educational Resources Information Center

Grochowalski, Joseph H.

2015-01-01

Component Universe Score Profile analysis (CUSP) is introduced in this paper as a psychometric alternative to multivariate profile analysis. The theoretical foundations of CUSP analysis are reviewed, which include multivariate generalizability theory and constrained principal components analysis. Because CUSP is a combination of generalizability…

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

PubMed

Lightner, A L; McKenna, N P; Tse, C S; Raffals, L E; Loftus, E V; Mathis, K L

2018-03-01

Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds. © 2017 John Wiley & Sons Ltd.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes

NASA Astrophysics Data System (ADS)

Wang, Qi; Grozdanic, Sinisa D.; Harper, Matthew M.; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Exploring Raman spectroscopy for the evaluation of glaucomatous retinal changes.

PubMed

Wang, Qi; Grozdanic, Sinisa D; Harper, Matthew M; Hamouche, Nicolas; Kecova, Helga; Lazic, Tatjana; Yu, Chenxu

2011-10-01

Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and subsequent loss of visual function. Early detection of glaucoma is critical for the prevention of permanent structural damage and irreversible vision loss. Raman spectroscopy is a technique that provides rapid biochemical characterization of tissues in a nondestructive and noninvasive fashion. In this study, we explored the potential of using Raman spectroscopy for detection of glaucomatous changes in vitro. Raman spectroscopic imaging was conducted on retinal tissues of dogs with hereditary glaucoma and healthy control dogs. The Raman spectra were subjected to multivariate discriminant analysis with a support vector machine algorithm, and a classification model was developed to differentiate disease tissues versus healthy tissues. Spectroscopic analysis of 105 retinal ganglion cells (RGCs) from glaucomatous dogs and 267 RGCs from healthy dogs revealed spectroscopic markers that differentiated glaucomatous specimens from healthy controls. Furthermore, the multivariate discriminant model differentiated healthy samples and glaucomatous samples with good accuracy [healthy 89.5% and glaucomatous 97.6% for the same breed (Basset Hounds); and healthy 85.0% and glaucomatous 85.5% for different breeds (Beagles versus Basset Hounds)]. Raman spectroscopic screening can be used for in vitro detection of glaucomatous changes in retinal tissue with a high specificity.

Partial Least Squares for Discrimination in fMRI Data

PubMed Central

Andersen, Anders H.; Rayens, William S.; Liu, Yushu; Smith, Charles D.

2011-01-01

Multivariate methods for discrimination were used in the comparison of brain activation patterns between groups of cognitively normal women who are at either high or low Alzheimer's disease risk based on family history and apolipoprotein-E4 status. Linear discriminant analysis (LDA) was preceded by dimension reduction using either principal component analysis (PCA), partial least squares (PLS), or a new oriented partial least squares (OrPLS) method. The aim was to identify a spatial pattern of functionally connected brain regions that was differentially expressed by the risk groups and yielded optimal classification accuracy. Multivariate dimension reduction is required prior to LDA when the data contains more feature variables than there are observations on individual subjects. Whereas PCA has been commonly used to identify covariance patterns in neuroimaging data, this approach only identifies gross variability and is not capable of distinguishing among-groups from within-groups variability. PLS and OrPLS provide a more focused dimension reduction by incorporating information on class structure and therefore lead to more parsimonious models for discrimination. Performance was evaluated in terms of the cross-validated misclassification rates. The results support the potential of using fMRI as an imaging biomarker or diagnostic tool to discriminate individuals with disease or high risk. PMID:22227352

Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD.

PubMed

de Bortoli, Nicola; Frazzoni, Leonardo; Savarino, Edoardo V; Frazzoni, Marzio; Martinucci, Irene; Jania, Aleksandra; Tolone, Salvatore; Scagliarini, Michele; Bellini, Massimo; Marabotto, Elisa; Furnari, Manuele; Bodini, Giorgia; Russo, Salvatore; Bertani, Lorenzo; Natali, Veronica; Fuccio, Lorenzo; Savarino, Vincenzo; Blandizzi, Corrado; Marchi, Santino

2016-12-01

We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE). IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

Stage Presentation, Care Patterns, and Treatment Outcomes for Squamous Cell Carcinoma of the Penis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burt, Lindsay M.; Shrieve, Dennis C.; Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu

Purpose: Penile squamous cell carcinoma (SCC) is a rare entity, with few published series on outcomes. We evaluated the stage distributions and outcomes for surgery and radiation therapy in a U.S. population database. Methods and Materials: Subjects with SCC of the penis were identified using the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program database between 1988 and 2006. Descriptive statistics were performed, and cause-specific survival (CSS) was estimated using Kaplan-Meier analysis. Comparisons of treatment modalities were analyzed using multivariate Cox regression. Subjects were staged using American Joint Committee on Cancer, sixth edition, criteria. Results: There were 2458more » subjects identified. The median age was 66.8 years (range, 17-102 years). Grade 2 disease was present in 94.5% of cases. T1, T2, T3, T4, and Tx disease was present in 64.8%, 17.1%, 9.5%, 2.1%, and 6.5% of cases, respectively. N0, N1, N2, N3, and Nx disease was noted in 61.6%, 6.9%, 4.0%, 3.7%, and 23.8% of cases, respectively. M1 disease was noted in 2.5% of subjects. Individuals of white ethnicity accounted for 85.1% of cases. Lymphadenectomy was performed in 16.7% of cases. The CSS for all patients at 5 and 10 years was 80.8% and 78.6%. By multivariable analysis grades 2 and 3 disease, T3 stage, and positive lymph nodes were adverse prognostic factors for CSS. Conclusion: SCC of the penis often presents as early-stage T1, N0, M0, grade 1, or grade 2 disease. The majority of patients identified were treated with surgery, and only a small fraction of patients received radiation therapy alone or as adjuvant therapy.« less

Prognostic capability of different liver disease scoring systems for prediction of early mortality after transjugular intrahepatic portosystemic shunt creation.

PubMed

Gaba, Ron C; Couture, Patrick M; Bui, James T; Knuttinen, M Grace; Walzer, Natasha M; Kallwitz, Eric R; Berkes, Jamie L; Cotler, Scott J

2013-03-01

To compare the performance of various liver disease scoring systems in predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, eight scoring systems were used to grade liver disease in 211 patients (male-to-female ratio = 131:80; mean age, 54 y) before TIPS creation from 1999-2011. Scoring systems included bilirubin level, Child-Pugh (CP) score, Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease sodium (MELD-Na) score, Emory score, prognostic index (PI), Acute Physiology and Chronic Health Evaluation (APACHE) 2 score, and Bonn TIPS early mortality (BOTEM) score. Medical record review was used to identify 30-day and 90-day clinical outcomes. The relationship of scoring parameters with mortality outcomes was assessed with multivariate analysis, and the relative ability of systems to predict mortality after TIPS creation was evaluated by comparing area under receiver operating characteristic (AUROC) curves. TIPS were successfully created for variceal hemorrhage (n = 121), ascites (n = 72), hepatic hydrothorax (n = 15), and portal vein thrombosis (n = 3). All scoring systems had a significant association with 30-day and 90-day mortality (P<.050 in each case) on multivariate analysis. Based on 30-day and 90-day AUROC, MELD (0.878, 0.816) and MELD-Na (0.863, 0.823) scores had the best capability to predict early mortality compared with bilirubin (0.786, 0.749), CP (0.822, 0.771), Emory (0.786, 0.681), PI (0.854, 0.760), APACHE 2 (0.836, 0.735), and BOTEM (0.798, 0.698), with statistical superiority over bilirubin, Emory, and BOTEM scores. Several liver disease scoring systems have prognostic value for early mortality after TIPS creation. MELD and MELD-Na scores most effectively predict survival after TIPS creation. Copyright © 2013. Published by Elsevier Inc.

Association between obesity and chronic periodontitis: a cross-sectional study.

PubMed

Palle, Ajay Reddy; Reddy, C M Sanjeeva Kumar; Shankar, B Shiva; Gelli, Vemsi; Sudhakar, Jaradoddi; Reddy, K Krishna Mohana

2013-03-01

Chronic periodontitis is multifactorial and numerous risk factors have been identified to contribute in the disease progression. Current study aimed to conduct a cross-sectional study in a population of patients with cardiovascular diseases in order to correlate the association between obesity [body mass index (BMI) and waist circumference (WC)] and periodontal disease parameters. The study was of a cross-sectional design and a total of 201 patients were examined after obtaining their informed consent. Subjects who had a history of cardiovascular diseases and under treatment were included in the study. Two indicators of obesity were used: BMI and WC. The following periodontal parameters were assessed: Probing depth, clinical attachment level. The oral hygiene status of the subjects was assessed by the oral hygiene index (OHI, simplified) given by John C Greene and Jack R Vermillion. The influence of the BMI and other confounding variables on periodontitis severity was assessed by multivariate logistic regression analysis. Data were analyzed using SPSS. Significant association was seen with low density lipoproteins (LDL) and severity of periodontitis (p < 0.005), triglyceride levels (TGL) and severity of periodontitis (p < 0.005), cholesterol and severity of periodontitis (p < 0.005), BMI and severity of periodontitis (p < 0.001), OHI and severity of periodontitis (p < 0.001). Significant association was seen with smoking and severity of periodontitis (p < 0.005), BMI and severity of periodontitis (p < 0.001), WC and severity of periodontitis (p < 0.001), cholesterol and severity of periodontitis (p < 0.001), OHI and severity of periodontitis (p < 0.001). Obesity has been implicated as a risk factor for several conditions including cardiovascular disease, diabetes, etc. In our study the relation between measures of overall and abdominal obesity (BMI and WC) and periodontal disease showed significant association in the multivariate logistic regression analysis independent of other confounding factors. Obesity can act as a significant risk factor in progression of periodontitis.

Use of proxy measures in estimating socioeconomic inequalities in malaria prevalence.

PubMed

Somi, Masha F; Butler, James R; Vahid, Farshid; Njau, Joseph D; Kachur, S P; Abdulla, Salim

2008-03-01

To present and compare socioeconomic status (SES) rankings of households using consumption and an asset-based index as two alternative measures of SES; and to compare and evaluate the performance of these two measures in multivariate analyses of the socioeconomic gradient in malaria prevalence. Data for the study come from a survey of 557 households in 25 study villages in Tanzania in 2004. Household SES was determined using consumption and an asset-based index calculated using Principal Components Analysis on a set of household variables. In multivariate analyses of malaria prevalence, we also used two other measures of disease prevalence: parasitaemia and self-report of malaria or fever in the 2 weeks before interview. Household rankings based on the two measures of SES differ substantially. In multivariate analyses, there was a statistically significant negative association between both measures of SES and parasitaemia but not between either measure of SES and self-reported malaria. Age of individual, use of a mosquito net, and wall construction were negatively and significantly associated with parasitaemia, whilst roof construction was positively associated with parasitaemia. Only age remained significant when malaria self-report was used as the measure of disease prevalence. An asset index is an effective alternative to consumption in measuring the socioeconomic gradient in malaria parasitaemia, but self-report may be an unreliable measure of malaria prevalence for this purpose.

The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: applying multivariate statistics to identify proteins with prognostic value and biological relevance.

PubMed

Heidema, A Geert; Thissen, Uwe; Boer, Jolanda M A; Bouwman, Freek G; Feskens, Edith J M; Mariman, Edwin C M

2009-06-01

In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease risk factors, men who died of CHD between initial participation (1987-1991) and end of follow-up (January 1, 2000) (N = 44) and matched controls (N = 44) were selected. Baseline plasma concentrations of proteins were measured by a multiplex immunoassay. With the use of PLS, we identified 15 proteins with prognostic value for CHD mortality and sets of proteins associated with the intermediate end points. Subsequently, sets of proteins and intermediate end points were analyzed together by Principal Components Analysis, indicating that proteins involved in inflammation explained most of the variance, followed by proteins involved in metabolism and proteins associated with total-C. This study is one of the first in which the association of a large number of plasma proteins with CHD mortality and intermediate end points is investigated by applying multivariate statistics, providing insight in the relationships among proteins, intermediate end points and CHD mortality, and a set of proteins with prognostic value.

Impact of involved field radiotherapy in partial response after doxorubicin-based chemotherapy for advanced aggressive non-Hodgkin's lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moser, Elizabeth C.; Kluin-Nelemans, Hanneke C.; Carde, Patrice

2006-11-15

Purpose: Whether salvage therapy in patients with advanced aggressive non-Hodgkin's lymphoma (NHL) in partial remission (PR) should consist of radiotherapy or autologous stem-cell transplantation (ASCT) is debatable. We evaluated the impact of radiotherapy on outcome in PR patients treated in four successive European Organization for Research and Treatment of Cancer trials for aggressive NHL. Patients and Methods: Records of 974 patients (1980-1999) were reviewed regarding initial response, final outcome, and type and timing of salvage treatment. After 8 cycles of doxorubicin-based chemotherapy, 227 NHL patients were in PR and treated: 114 received involved field radiotherapy, 16 ASCT, 93 second-line chemotherapy,more » and 4 were operated. Overall survival (OS) and progression-free survival (PFS) after radiotherapy were estimated (Kaplan-Meier method) and compared with other treatments (log-rank). Impact on survival was evaluated by multivariate analysis (Cox proportional hazards model). Results: The median PFS in PR patients was 4.2 years and 48% remained progression-free at 5 years. Half of the PR patients converted to a complete remission. After conversion, survival was comparable to patients directly in complete remission. Radiotherapy resulted in better OS and PFS compared with other treatments, especially in patients with low to intermediate International Prognostic Index score, bulky disease, or nodal disease only. Correction by multivariate analysis for prognostic factors such as stage, bulky disease, and number of extranodal locations showed that radiotherapy was clearly the most significant factor affecting both OS and PFS. Conclusion: This retrospective analysis demonstrates that radiotherapy can be effective for patients in PR after fully dosed chemotherapy; assessment in a randomized trial (radiotherapy vs. ASCT) is justified.« less

Predictive Utility of Marketed Volumetric Software Tools in Subjects at Risk for Alzheimer's: Do Regions Outside the Hippocampus Matter?

PubMed Central

Tanpitukpongse, Teerath P.; Mazurowski, Maciej A.; Ikhena, John; Petrella, Jeffrey R.

2016-01-01

Background and Purpose To assess prognostic efficacy of individual versus combined regional volumetrics in two commercially-available brain volumetric software packages for predicting conversion of patients with mild cognitive impairment to Alzheimer's disease. Materials and Methods Data was obtained through the Alzheimer's Disease Neuroimaging Initiative. 192 subjects (mean age 74.8 years, 39% female) diagnosed with mild cognitive impairment at baseline were studied. All had T1WI MRI sequences at baseline and 3-year clinical follow-up. Analysis was performed with NeuroQuant® and Neuroreader™. Receiver operating characteristic curves assessing the prognostic efficacy of each software package were generated using a univariable approach employing individual regional brain volumes, as well as two multivariable approaches (multiple regression and random forest), combining multiple volumes. Results On univariable analysis of 11 NeuroQuant® and 11 Neuroreader™ regional volumes, hippocampal volume had the highest area under the curve for both software packages (0.69 NeuroQuant®, 0.68 Neuroreader™), and was not significantly different (p > 0.05) between packages. Multivariable analysis did not increase the area under the curve for either package (0.63 logistic regression, 0.60 random forest NeuroQuant®; 0.65 logistic regression, 0.62 random forest Neuroreader™). Conclusion Of the multiple regional volume measures available in FDA-cleared brain volumetric software packages, hippocampal volume remains the best single predictor of conversion of mild cognitive impairment to Alzheimer's disease at 3-year follow-up. Combining volumetrics did not add additional prognostic efficacy. Therefore, future prognostic studies in MCI, combining such tools with demographic and other biomarker measures, are justified in using hippocampal volume as the only volumetric biomarker. PMID:28057634

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis.

PubMed

Lee, Shina; Ryu, Jung Hwa; Kim, Seung Jung; Ryu, Dong Ryeol; Kang, Duk Hee; Choi, Kyu Bok

2016-11-01

Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin). This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.

Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors

PubMed Central

Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

2014-01-01

Background Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. Objective To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Methods Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. Results We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. Conclusions In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases. PMID:25759803

[The value of SYNTAX score in predicting outcome patients undergoing percutaneous coronary intervention].

PubMed

Gao, Yue-chun; Yu, Xian-peng; He, Ji-qiang; Chen, Fang

2012-01-01

To assess the value of SYNTAX score to predict major adverse cardiac and cerebrovascular events (MACCE) among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. 190 patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention (PCI) with Cypher select drug-eluting stent were enrolled. SYNTAX score and clinical SYNTAX score were retrospectively calculated. Our clinical Endpoint focused on MACCE, a composite of death, nonfatal myocardial infarction (MI), stroke and repeat revascularization. The value of SYNTAX score and clinical SYNTAX score to predict MACCE were studied respectively. 29 patients were observed to suffer from MACCE, accounting 18.5% of the overall 190 patients. MACCE rates of low (≤ 20.5), intermediate (21.0 - 31.0), and high (≥ 31.5) tertiles according to SYNTAX score were 9.1%, 16.2% and 30.9% respectively. Both univariate and multivariate analysis showed that SYNTAX score was the independent predictor of MACCE. MACCE rates of low (≤ 19.5), intermediate (19.6 - 29.1), and high (≥ 29.2) tertiles according to clinical SYNTAX score were 14.9%, 9.8% and 30.6% respectively. Both univariate and multivariate analysis showed that clinical SYNTAX score was the independent predictor of MACCE. ROC analysis showed both SYNTAX score (AUC = 0.667, P = 0.004) and clinical SYNTAX score (AUC = 0.636, P = 0.020) had predictive value of MACCE. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score. Both SYNTAX score and clinical SYNTAX score could be independent risk predictors for MACCE among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score in this group of patients.

Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis.

PubMed

Winters, Brian R; Mossanen, Matthew; Holt, Sarah K; Lin, Daniel W; Wright, Jonathan L

2016-10-01

To examine the risk factors associated with upstaging at inguinal lymph node dissection (ILND) in men with penile cancer and clinically negative lymph nodes (cN0) using a large US cancer database. The National Cancer Data Base was queried from 1998 to 2012 to identify men with penile cancer who underwent ILND and had complete clinical or pathologic node status available. Lymphovascular invasion (LVI) was available after 2010. Multivariate logistic regression evaluated factors (cT stage, grade, LVI) associated with pathologic nodal upstaging in those with cN0 disease. Correlations between clinical and pathologic node status were also calculated with weighted kappa statistics. Complete clinical and pathologic LN status was available for 875 patients. Of these, 461 (53%) were cN0. Upstaging occurred in 111 (24%). When stratified by low, intermediate, and high-risk groups, the proportion with pathologically positive LNs was 16%, 20%, and 27%, respectively (P = .12). On multivariate analysis, limited to men with LVI data available (N = 206), LVI (odds ratio 3.10, 95% confidence interval 1.39-6.92), but not increasing stage (univariate only) or grade (univariate only), was significantly associated with upstaging at ILND. In this analysis, of 461 patients with node-negative penile cancer undergoing ILND, upstaging was observed in 24%. LVI was the strongest independent predictor of occult lymph node disease. These findings corroborate the presence of LVI as the significant risk factor for occult micrometastases and suggest a possible improvement in existing risk stratification groupings, with the presence of LVI, regardless of stage or grade, to be considered high-risk disease. Copyright © 2016 Elsevier Inc. All rights reserved.

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis

PubMed Central

Lee, Shina; Ryu, Jung-Hwa; Kim, Seung-Jung; Ryu, Dong-Ryeol; Kang, Duk-Hee

2016-01-01

Purpose Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). Materials and Methods A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. Results In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin). Conclusion This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients. PMID:27593873

Diabetic peripheral neuropathy in ambulatory patients with type 2 diabetes in a general hospital in a middle income country: a cross-sectional study.

PubMed

Lazo, María de Los Angeles; Bernabé-Ortiz, Antonio; Pinto, Miguel E; Ticse, Ray; Malaga, German; Sacksteder, Katherine; Miranda, J Jaime; Gilman, Robert H

2014-01-01

We aimed to estimate the morbidity rate and associated factors for diabetic peripheral neuropathy (DPN) in a low-middle income country setting. Cross-sectional study, data was gathered at Peru's Ministry of Health national specialized hospital for endocrinological conditions through standardized interviews, anthropometric measurements and blood tests for glycated haemoglobin (HbA1c). DPN was evaluated using two techniques: the Semmes-Weinstein monofilament test and the diabetic neuropathy symptom score. Overall prevalence and 95% confidence intervals (95% CI) were calculated. Potential factors related to DPN explored included body mass index, years with disease (<10 vs. ≥10 years), glycaemic control (HbA1c <7% vs. ≥7%), microalbuminuria, retinopathy, and current pharmacological treatment. Multivariable analysis was performed using Poisson analysis to calculate prevalence ratios. DPN was observed in 73/129 (56.6%) patients. In multivariable analysis adjusted by age and sex, the prevalence ratio of neuropathy was 1.4 times higher (95% CI 1.07-1.88) in patients who took insulin plus metformin compared to patients who used one treatment alone, and 1.4 higher (95% CI 1.02-1.93) in patients with ≥10 years of disease compared to those with a shorter duration of disease. Also we found some characteristics in foot evaluation associated to neuropathy such as deformities (p<0.001), onychomycosis (p = 0.012), abnormal Achilles reflex (p<0.001), pain perception (p<0.001) and vibration perception (p<0.001). DPN is highly frequent among patients with diabetes in a national specialized facility from Peru. Associated factors to DPN included being a diabetic patient for over ten years, and receiving insulin plus metformin.

The association of poverty with the prevalence of albuminuria: data from the Third National Health and Nutrition Examination Survey (NHANES III).

PubMed

Martins, David; Tareen, Naureen; Zadshir, Ashraf; Pan, Deyu; Vargas, Roberto; Nissenson, Allen; Norris, Keith

2006-06-01

Albuminuria is a major risk factor for the development and progression of chronic kidney disease (CKD) and cardiovascular disease. Socioeconomic factors also have been reported to modify CKD and cardiovascular risk factors and clinical outcomes. The extent to which poverty influences the prevalence of albuminuria, particularly among racial/ethnic minority populations, is not well established. The influence of poverty on the prevalence of albuminuria and the implication of this relationship for the racial and/or ethnic differences in the prevalence of albuminuria were examined. We examined data from 6,850 male and 7,634 female adults from a national probability survey conducted between 1988 and 1994. In univariate analysis, poverty, defined as less than 200% federal poverty level (FPL), was associated with the presence of both microalbuminuria (odds ratio [OR], 1.35; 95% confidence interval, 1.22 to 1.49) and macroalbuminuria (OR, 1.78; 95% confidence interval, 1.40 to 2.26). The association of less than 200% FPL with microalbuminuria persisted in a multivariate model controlling for age, sex, race, education, obesity, hypertension, diabetes, reduced glomerular filtration rate, and medication use (OR, 1.18; 95% confidence interval, 1.05 to 1.33). FPL less than 200% was not associated with macroalbuminuria in the multivariate model. When multivariate analysis is stratified by FPL (<200% and > or =200%), differences in ORs for microalbuminuria and macroalbuminuria among racial/ethnic minority participants compared with whites were more apparent among the less affluent participants in the FPL-less-than-200% stratum. FPL less than 200% is associated with microalbuminuria, and differences in FPL levels may account for some of the observed differences in prevalence of albuminuria between racial/ethnic minority participants and their white counterparts.

Neuropsychological Testing Predicts Cerebrospinal Fluid Aβ in Mild Cognitive Impairment (MCI)

PubMed Central

Kandel, Benjamin M.; Avants, Brian B.; Gee, James C.; Arnold, Steven E.; Wolk, David A.

2015-01-01

Background Psychometric tests predict conversion of Mild Cognitive Impairment (MCI) to probable Alzheimer's Disease (AD). Because the definition of clinical AD relies on those same psychometric tests, the ability of these tests to identify underlying AD pathology remains unclear. Objective To determine the degree to which psychometric testing predicts molecular evidence of AD amyloid pathology, as indicated by CSF Aβ1–42, in patients with MCI, as compared to neuroimaging biomarkers. Methods We identified 408 MCI subjects with CSF Aβ levels, psychometric test data, FDG-PET scans, and acceptable volumetric MR scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We used psychometric tests and imaging biomarkers in univariate and multivariate models to predict Aβ status. Results The 30-minute delayed recall score of the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of Aβ status among the psychometric tests, achieving an AUC of 0.67±0.02 and odds ratio of 2.5±0.4. FDG-PET was the best imaging-based biomarker (AUC 0.67±0.03, OR 3.2±1.2), followed by hippocampal volume (AUC 0.64±0.02,,OR 2.4±0.3). A multivariate analysis based on the psychometric tests improved on the univariate predictors, achieving an AUC of 0.68±0.03 (OR 3.38±1.2). Adding imaging biomarkers to the multivariate analysis did not improve the AUC. Conclusion Psychometric tests perform as well as imaging biomarkers to predict presence of molecular markers of AD pathology in MCI patients and should be considered in the determination of the likelihood that MCI is due to AD. PMID:25881908

The effects of aminosalicylates or thiopurines on the risk of colorectal cancer in inflammatory bowel disease.

PubMed

Carrat, F; Seksik, P; Colombel, J-F; Peyrin-Biroulet, L; Beaugerie, L

2017-02-01

Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial. To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5-ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates (OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines (OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468). In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines. © 2016 John Wiley & Sons Ltd.

Predictors of Depression in Youth With Crohn Disease

PubMed Central

Clark, Jeffrey G.; Srinath, Arvind I.; Youk, Ada O.; Kirshner, Margaret A.; McCarthy, F. Nicole; Keljo, David J.; Bousvaros, Athos; DeMaso, David R.; Szigethy, Eva M.

2014-01-01

Objective The aim of the study was to determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn disease (CD). Methods A total of 550 (n = 550) youth ages 9 to 17 years with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized controlled trial. Out of the 550, 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children’s Depression Inventory (CDI). A child or parent CDI score ≥ 12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn’s Disease Activity Index (PCDAI) were collected as the potential predictors of depression. Univariate regression models were constructed to determine the relations among predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relation between infliximab use and depression while controlling for other predictors of depression. Results Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (P<0.01) and negatively associated with socioeconomic status (SES) (P<0.001). In multivariate models, PCDAI and SES were the strongest predictors of depression. Conclusions Disease activity and SES are significant predictors of depression in youth with Crohn disease. PMID:24343281

Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response.

PubMed

van Vollenhoven, Ronald F; Petri, Michelle A; Cervera, Ricard; Roth, David A; Ji, Beulah N; Kleoudis, Christi S; Zhong, Z John; Freimuth, William

2012-08-01

To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets. The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect. Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA-SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA-SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life. These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline. CLINICALTRIALS.GOV: identifiers NCT00424476 and NCT00410384.

Surgical Treatment of Metastatic Ovarian Tumors From Extragenital Primary Sites.

PubMed

Sal, Veysel; Demirkiran, Fuat; Topuz, Samet; Kahramanoglu, Ilker; Yalcin, Ibrahim; Bese, Tugan; Sozen, Hamdullah; Tokgozoglu, Nedim; Salihoglu, Yavuz; Turan, Hasan; Iyibozkurt, Cem; Kolomuc, Tugba; Sofiyeva, Nigar; Berkman, Sinan; Arvas, Macit

2016-05-01

The purpose of this study was to investigate the outcomes and prognostic factors of metastasectomy in patients with metastatic ovarian tumors from extragenital primary sites. All patients with pathologically confirmed metastatic ovarian tumors between January 1997 and June 2015 were included in this study. A total of 131 patients were identified. The data were obtained from the patients' medical records. Clinicopathological features were evaluated by both univariate and multivariate analyses. The primary sites were colorectal region (53.4%), stomach (26%), and breast (13%). Preoperative serum CA 125 and CA 19-9 levels were elevated in 29.4% and 39.8% of the patients, respectively. Cytoreductive surgery was performed in 41.2% of the patients. Seventy-three (55.7%) patients had no residual disease after surgery. Sixty-six (49.6%) patients had combined metastases at the time of the surgery to sites including the liver, pancreas, lung, bone, lymph nodes, bladder, or the intestine. With a median follow-up of 33 months, the median survival time was 22 months. The estimated 5-year survival probability is 0.26. On univariate analysis, primary cancer site, combined metastasis outside the ovaries, residual disease, preoperative serum CA 125 and CA 19-9 levels, and histologic type were significant parameters for overall survival. Furthermore, residual disease, preoperative serum CA 19-9 level, and primary cancer site were found to be independent prognostic factors on multivariate analysis. The most common primary sites for ovarian metastasis are gastrointestinal tract. Metastasectomy may have beneficial effects on survival, especially if the residual disease is less than 5 mm. Prospective studies warranted to evaluate the value of metastasectomy in patients with ovarian metastasis.

Impact of Preoperative Abdominal Visceral Adipose Tissue Area and Nutritional Status on Renal Function After Donor Nephrectomy in Japanese Living Donors for Renal Transplantation.

PubMed

Hori, Shunta; Miyake, Makito; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Tanaka, Nobumichi; Yoshida, Katsunori; Fujimoto, Kiyohide

2018-05-29

BACKGROUND Living kidney donors face the risk of renal dysfunction, resulting in end-stage renal disease, cardiovascular disease, or cerebrovascular disease, after donor nephrectomy. Reducing this risk is important to increasing survival of living donors. In this study, we investigated the effect of preoperative distribution of abdominal adipose tissue and nutritional status on postoperative renal function in living donors. MATERIAL AND METHODS Seventy-five living donors were enrolled in this retrospective study. Preoperative unenhanced computed tomography images were used to measure abdominal adipose tissue parameters. Prognostic nutritional index (PNI) was used to assess preoperative nutritional status. Donors were divided into 2 groups according to abdominal visceral adipose tissue (VAT) area at the level of the fourth and fifth lumbar vertebrae (<80 or ≥80 cm²). Postoperative renal function was compared in the 2 groups, and prognostic factors for development of chronic kidney disease (CKD) G3b were identified using multivariate analysis. RESULTS Donors with a VAT area ≥80 significantly more often had hypertension preoperatively. Although there was no significant difference in preoperative estimated glomerular filtration rate (eGFR) between the 2 groups, postoperative renal function was significantly decreased in donors with a VAT area ≥80 compared to those with a VAT area <80. In multivariate analysis, VAT area ≥80 and PNI <54 were independent factors predicting the development of CKD G3b after 12 months. CONCLUSIONS Our findings suggest that preoperative VAT and PNI affect postoperative renal function. Further research is required to establish appropriate exercise protocols and nutritional interventions during follow-up to improve outcomes in living donors.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Impact of sinonasal disease on depression, sleep duration, and productivity among adults in the United States.

PubMed

Zhou, Sheng; Hur, Kevin; Shen, Jasper; Wrobel, Bozena

2017-10-01

Examine the relationship between depression symptoms and sinonasal inflammatory diseases, and investigate health disparities associated with allergic rhinitis (AR) and sinusitis in the United States. Cross-sectional analysis of 2014 National Health Interview Survey (NHIS) data. Adult cases of AR and sinusitis were extracted from the 2014 NHIS in addition to demographic, socioeconomic, and related depressive symptom data. The dataset was analyzed with chi-square, t-tests, and multivariate regression. There were 19.1 ± 1.1 million adult AR cases and 29.4 ± 1.4 million adult sinusitis cases. Of these, 20.6% and 22.0% reported depression symptoms in the past 12 months for those with AR or sinusitis, respectively. Both diseases were also associated with significantly fewer mean hours of sleep a night (AR: 7.02 vs. 7.14, P  < 0.01; Sinusitis: 6.98 vs. 7.14, P  < 0.01) and greater mean days of work missed (AR: 4.60 vs. 3.62, P  < 0.01; Sinusitis: 5.87 vs. 3.41; P  < 0.01). On multivariate analysis, the prevalence of AR and sinusitis was significantly higher among men, Caucasians, older adults, the more educated, and adults with depression symptoms. Only the prevalence of sinusitis varied depending on income and geography. Allergic rhinitis and sinusitis are associated with an increased likelihood of depressive symptoms, shorter sleep duration, and more workdays lost. The prevalence of both are influenced by age, sex, race/ethnicity, and education level. Targeted initiatives should be developed to address these health disparities and comorbidities associated with inflammatory sinonasal disease. 4.

Diagnosis of rheumatoid arthritis: multivariate analysis of biomarkers.

PubMed

Wild, Norbert; Karl, Johann; Grunert, Veit P; Schmitt, Raluca I; Garczarek, Ursula; Krause, Friedemann; Hasler, Fritz; van Riel, Piet L C M; Bayer, Peter M; Thun, Matthias; Mattey, Derek L; Sharif, Mohammed; Zolg, Werner

2008-02-01

To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of rheumatoid arthritis (RA) depending on the diagnostic situation. Biomarkers were subject to three inclusion/exclusion criteria (discrimination between RA patients and healthy blood donors, ability to identify anti-CCP-negative RA patients, specificity in a panel with major non-rheumatological diseases) before univariate ranking and multivariate analysis was carried out using a modelling panel (n = 906). To enable the evaluation of the classification power in different diagnostic settings the disease controls (n = 542) were weighted according to the admission rates in rheumatology clinics modelling a clinic panel or according to the relative prevalences of musculoskeletal disorders in the general population seen by general practitioners modelling a GP panel. Out of 131 biomarkers considered originally, we evaluated 32 biomarkers in this study, of which only seven passed the three inclusion/exclusion criteria and were combined by multivariate analysis using four different mathematical models. In the modelled clinic panel, anti-CCP was the lead marker with a sensitivity of 75.8% and a specificity of 94.0%. Due to the lack in specificity of the markers other than anti-CCP in this diagnostic setting, any gain in sensitivity by any marker combination is off-set by a corresponding loss in specificity. In the modelled GP panel, the best marker combination of anti-CCP and interleukin (IL)-6 resulted in a sensitivity gain of 7.6% (85.9% vs. 78.3%) at a minor loss in specificity of 1.6% (90.3% vs. 91.9%) compared with anti-CCP as the best single marker. Depending on the composition of the sample panel, anti-CCP alone or anti-CCP in combination with IL-6 has the highest classification power for the diagnosis of established RA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morganti, Alessio G.; Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso; Falconi, Massimo

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462more » patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.« less

CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence.

PubMed

Kurnit, Katherine C; Kim, Grace N; Fellman, Bryan M; Urbauer, Diana L; Mills, Gordon B; Zhang, Wei; Broaddus, Russell R

2017-07-01

Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46-200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. In all, 342 patients were identified, 245 of which had endometrioid histology. For grades 1-2, stages I-II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03-1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69-13.21), and TP53 mutation (HR 4.07, 95% CI 1.57-10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grades 1-2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38-9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.

Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia.

PubMed

Al Ghamdi, Mohammed; Alghamdi, Khalid M; Ghandoora, Yasmeen; Alzahrani, Ameera; Salah, Fatmah; Alsulami, Abdulmoatani; Bawayan, Mayada F; Vaidya, Dhananjay; Perl, Trish M; Sood, Geeta

2016-04-21

Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.

Medical risk factors for severe West Nile Virus disease, United States, 2008-2010.

PubMed

Lindsey, Nicole P; Staples, J Erin; Lehman, Jennifer A; Fischer, Marc

2012-07-01

We conducted enhanced surveillance to identify medical risk factors for severe illness (i.e., hospitalization or death) and neuroinvasive disease (i.e., encephalitis or meningitis) among all West Nile virus disease cases reported from selected states from 2008 to 2010. Of the 1,090 case-patients included in the analysis, 708 (65%) case-patients were hospitalized, 641 (59%) case-patients had neuroinvasive disease, and 55 (5%) case-patients died. Chronic renal disease (adjusted odds ratio [aOR] = 4.1; 95% confidence interval [CI] = 1.4-12.1), history of cancer (aOR = 3.7; 95% CI = 1.8-7.5), history of alcohol abuse (aOR = 3.0; 95% CI = 1.3-6.7), diabetes (aOR = 2.2; 95% CI = 1.4-3.4), and hypertension (aOR = 1.5; 95% CI = 1.1-2.1) were independently associated with severe illness on multivariable analysis. Although the same medical conditions were independently associated with encephalitis, only hypertension was associated with meningitis. The only condition independently associated with death was immune suppression. Prevention messages should be targeted to persons with these conditions.

Multivariate meta-analysis: potential and promise.

PubMed

Jackson, Dan; Riley, Richard; White, Ian R

2011-09-10

The multivariate random effects model is a generalization of the standard univariate model. Multivariate meta-analysis is becoming more commonly used and the techniques and related computer software, although continually under development, are now in place. In order to raise awareness of the multivariate methods, and discuss their advantages and disadvantages, we organized a one day 'Multivariate meta-analysis' event at the Royal Statistical Society. In addition to disseminating the most recent developments, we also received an abundance of comments, concerns, insights, critiques and encouragement. This article provides a balanced account of the day's discourse. By giving others the opportunity to respond to our assessment, we hope to ensure that the various view points and opinions are aired before multivariate meta-analysis simply becomes another widely used de facto method without any proper consideration of it by the medical statistics community. We describe the areas of application that multivariate meta-analysis has found, the methods available, the difficulties typically encountered and the arguments for and against the multivariate methods, using four representative but contrasting examples. We conclude that the multivariate methods can be useful, and in particular can provide estimates with better statistical properties, but also that these benefits come at the price of making more assumptions which do not result in better inference in every case. Although there is evidence that multivariate meta-analysis has considerable potential, it must be even more carefully applied than its univariate counterpart in practice. Copyright © 2011 John Wiley & Sons, Ltd.

Relationship Between Body Mass Index and Proteinuria in Hypertensive Nephrosclerosis: Results From the African American Study of Kidney Disease and Hypertension (AASK) Cohort

PubMed Central

Toto, Robert D.; Greene, Tom; Hebert, Lee A.; Hiremath, Leena; Lea, Janice P.; Lewis, Julia B.; Pogue, Velvie; Sika, Mohammed; Wang, Xuelei

2011-01-01

Background Few studies have examined the association between obesity and markers of kidney injury in a chronic kidney disease population. We hypothesized that obesity is independently associated with proteinuria, a marker of chronic kidney disease progression. Study Design Observational cross-sectional analysis. Setting & Participants Post hoc analysis of baseline data for 652 participants in the African American Study of Kidney Disease (AASK). Predictors Obesity, determined using body mass index (BMI). Measurements & Outcomes Urine total protein–creatinine ratio and albumin-creatinine ratio measured in 24-hour urine collections. Results AASK participants had a mean age of 60.2 ± 10.2 years and serum creatinine level of 2.3 ± 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 ± 7.0 kg/m2. Approximately 70% of participants had a daily urine total protein excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2-kg/m2 increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4% (95% CI, 4.9-14.1) increase in urine total protein–creatinine and urine albumin-creatinine ratios, respectively. In multivari-able models adjusting for age, sex, systolic blood pressure, serum glucose level, uric acid level, and creatinine level, each 2-kg/m2 increase in BMI was associated with a 3.5% (95% CI, 0.4-6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria, respectively. The interaction between older age and BMI was statistically significant, indicating that this relationship was driven by younger AASK participants. Limitations May not generalize to other populations; cross-sectional analysis precludes statements regarding causality. Conclusions BMI is associated independently with urine total protein and albumin excretion in African Americans with hypertensive nephrosclerosis, particularly in younger patients. PMID:20801567

Likelihood of Incomplete Kidney Tumor Ablation with Radio Frequency Energy: Degree of Enhancement Matters.

PubMed

Lay, Aaron H; Stewart, Jeremy; Canvasser, Noah E; Cadeddu, Jeffrey A; Gahan, Jeffrey C

2016-07-01

Larger size and clear cell histopathology are associated with worse outcomes for malignant renal tumors treated with radio frequency ablation. We hypothesize that greater tumor enhancement may be a risk factor for radio frequency ablation failure due to increased vascularity. A retrospective review of patients who underwent radio frequency ablation for renal tumors with contrast enhanced imaging available was performed. The change in Hounsfield units (HU) of the tumor from the noncontrast phase to the contrast enhanced arterial phase was calculated. Radio frequency ablation failure rates for biopsy confirmed malignant tumors were compared using the chi-squared test. Multivariate logistic analysis was performed to assess predictive variables for radio frequency ablation failure. Disease-free survival was calculated using Kaplan-Meier analysis. A total of 99 patients with biopsy confirmed malignant renal tumors and contrast enhanced imaging were identified. The incomplete ablation rate was significantly lower for tumors with enhancement less than 60 vs 60 HU or greater (0.0% vs 14.6%, p=0.005). On multivariate logistic regression analysis tumor enhancement 60 HU or greater (OR 1.14, p=0.008) remained a significant predictor of incomplete initial ablation. The 5-year disease-free survival for size less than 3 cm was 100% vs 69.2% for size 3 cm or greater (p <0.01), while 5-year disease-free survival for HU change less than 60 was 100% vs 92.4% for HU change 60 or greater (p=0.24). Biopsy confirmed malignant renal tumors, which exhibit a change in enhancement of 60 HU or greater, experience a higher rate of incomplete initial tumor ablation than tumors with enhancement less than 60 HU. Size 3 cm or greater portends worse 5-year disease-free survival after radio frequency ablation. The degree of enhancement should be considered when counseling patients before radio frequency ablation. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas.

PubMed

González-Arriagada, Wilfredo A; Lozano-Burgos, Carlos; Zúñiga-Moreta, Rodrigo; González-Díaz, Paulina; Coletta, Ricardo D

2018-05-24

Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival. These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.

PubMed

Thompson, Philip A; O'Brien, Susan M; Xiao, Lianchun; Wang, Xuemei; Burger, Jan A; Jain, Nitin; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Wierda, William G

2016-02-15

A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date. The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes. B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]). Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. © 2015 American Cancer Society.

Analysis of serum from type II diabetes mellitus and diabetic complication using surface-enhanced Raman spectra (SERS)

NASA Astrophysics Data System (ADS)

Han, H. W.; Yan, X. L.; Dong, R. X.; Ban, G.; Li, K.

2009-03-01

In this paper, we show surface-enhanced Raman spectra (SERS) of serums from type II diabetes mellitus and diabetic complication (coronary disease, glaucoma and cerebral infarction), and analyze the SERS through the multivariate statistical methods of principal component analysis (PCA). In particular, we find that there exist many adenines in these serums, which maybe come from DNA (RNA) damage. The relative intensity of the band at 725±2 cm-1 assigned to adenine is higher for patients than for the healthy volunteers; therefore, it can be used as an important ‘fingerprint’ in order to diagnose these diseases. It is also shown that serums from type II diabetes mellitus group, diabetic complication group and healthy volunteers group can be discriminated by PCA.

Performance of the disease risk score in a cohort study with policy-induced selection bias.

PubMed

Tadrous, Mina; Mamdani, Muhammad M; Juurlink, David N; Krahn, Murray D; Lévesque, Linda E; Cadarette, Suzanne M

2015-11-01

To examine the performance of the disease risk score (DRS) in a cohort study with evidence of policy-induced selection bias. We examined two cohorts of new users of bisphosphonates. Estimates for 1-year hip fracture rates between agents using DRS, exposure propensity scores and traditional multivariable analysis were compared. The results for the cohort with no evidence of policy-induced selection bias showed little variation across analyses (-4.1-2.0%). Analysis of the cohort with evidence of policy-induced selection bias showed greater variation (-13.5-8.1%), with the greatest difference seen with DRS analyses. Our findings suggest that caution may be warranted when using DRS methods in cohort studies with policy-induced selection bias, further research is needed.

Multivariate analyses of peripheral blood leukocyte transcripts distinguish Alzheimer's, Parkinson's, control, and those at risk for developing Alzheimer's.

PubMed

Delvaux, Elaine; Mastroeni, Diego; Nolz, Jennifer; Chow, Nienwen; Sabbagh, Marwan; Caselli, Richard J; Reiman, Eric M; Marshall, Frederick J; Coleman, Paul D

2017-10-01

The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples. Rather than a single study with no replicates, we chose an experimental design in which there were multiple replicates using different platforms and different sample populations. We have divided 177 blood samples and 27 brain samples into multiple replicates to demonstrate the ability to distinguish early clinical AD (Clinical Dementia Rating scale 0.5), Parkinson's disease (PD), and cognitively unimpaired APOE4 homozygotes, as well as to determine persons at risk for future cognitive impairment with significant accuracy. We assess our methods in a training/test set and also show that the variables we use distinguish AD, PD, and control brain. Importantly, we describe the variability of the weights assigned to individual transcripts in multivariate analyses in repeated studies and suggest that the variability we describe may be the cause of inability to repeat many earlier studies. Our data constitute a proof of principle that multivariate analysis of the transcriptome related to cell stress and inflammation of peripheral blood leukocytes has significant potential as a minimally invasive and inexpensive diagnostic tool for diagnosis and early detection of risk for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting trauma patient mortality: ICD [or ICD-10-AM] versus AIS based approaches.

PubMed

Willis, Cameron D; Gabbe, Belinda J; Jolley, Damien; Harrison, James E; Cameron, Peter A

2010-11-01

The International Classification of Diseases Injury Severity Score (ICISS) has been proposed as an International Classification of Diseases (ICD)-10-based alternative to mortality prediction tools that use Abbreviated Injury Scale (AIS) data, including the Trauma and Injury Severity Score (TRISS). To date, studies have not examined the performance of ICISS using Australian trauma registry data. This study aimed to compare the performance of ICISS with other mortality prediction tools in an Australian trauma registry. This was a retrospective review of prospectively collected data from the Victorian State Trauma Registry. A training dataset was created for model development and a validation dataset for evaluation. The multiplicative ICISS model was compared with a worst injury ICISS approach, Victorian TRISS (V-TRISS, using local coefficients), maximum AIS severity and a multivariable model including ICD-10-AM codes as predictors. Models were investigated for discrimination (C-statistic) and calibration (Hosmer-Lemeshow statistic). The multivariable approach had the highest level of discrimination (C-statistic 0.90) and calibration (H-L 7.65, P= 0.468). Worst injury ICISS, V-TRISS and maximum AIS had similar performance. The multiplicative ICISS produced the lowest level of discrimination (C-statistic 0.80) and poorest calibration (H-L 50.23, P < 0.001). The performance of ICISS may be affected by the data used to develop estimates, the ICD version employed, the methods for deriving estimates and the inclusion of covariates. In this analysis, a multivariable approach using ICD-10-AM codes was the best-performing method. A multivariable ICISS approach may therefore be a useful alternative to AIS-based methods and may have comparable predictive performance to locally derived TRISS models. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Determinants of public phobia about infectious diseases in South Korea: effect of health communication and gender difference.

PubMed

Jung, Minsoo; Choi, Mankyu; Lee, Tae-Ro

2015-03-01

This study investigated the individual and social determinants of the public's phobia of infectious diseases in South Korea, where collective action was recently fueled by the public phobia over mad cow disease (bovine spongiform encephalopathy [BSE]). Gender-specific multivariate regression was used to compare the public perception of BSE and highly pathogenic avian influenza (HPAI). The analysis results differentiated between the determinants of the phobia for the 2 diseases, BSE and HPAI (N = 1002). As with HIV/AIDS and leprosy, the public fear of HPAI was expressed as a disease phobia that seeks to ensure the social exclusion of infection sources, whereas the fear of BSE was influenced by social and communication factors. Therefore, BSE, unlike previous HPAI, can be rapidly amplified amid the growing distrust in health communication, in which case the social determinants of disease phobia are associated with communicator trust, social values, and political attitude toward diseases rather than disease perception. © 2013 APJPH.

Extensions to Multivariate Space Time Mixture Modeling of Small Area Cancer Data.

PubMed

Carroll, Rachel; Lawson, Andrew B; Faes, Christel; Kirby, Russell S; Aregay, Mehreteab; Watjou, Kevin

2017-05-09

Oral cavity and pharynx cancer, even when considered together, is a fairly rare disease. Implementation of multivariate modeling with lung and bronchus cancer, as well as melanoma cancer of the skin, could lead to better inference for oral cavity and pharynx cancer. The multivariate structure of these models is accomplished via the use of shared random effects, as well as other multivariate prior distributions. The results in this paper indicate that care should be taken when executing these types of models, and that multivariate mixture models may not always be the ideal option, depending on the data of interest.

Prognostic predictors of patients with carcinoma of the gastric cardia.

PubMed

Zhang, Ming; Li, Zhigao; Ma, Yan; Zhu, Guanyu; Zhang, Hongfeng; Xue, Yingwei

2012-05-01

This study gives insight into survival predictors and clinicopathological features of carcinoma of the gastric cardia. The study included 233 patients who underwent operation for carcinoma of the gastric cardia. Clinicopathological prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. Cox regression was used for multivariate analysis and survival curves were drawn by the Kaplan- Meier method. Carcinoma of the gastric cardia was characterized by positive lymph node metastasis (77.3%), serosal invasion (83.3%) and more stage III or IV tumors (72.5%). Overall 5-year survival rate was 21.9% and median survival period was 24 months. The 5-year survival rate was influenced by tumor size, depth on invasion, lymph node metastasis, extent of lymph node dissection, disease stage, operation methods and resection margin. The absent of serosal invasion and lymph node metastasis, curative resection should be considered to be the favourable predictors of long-term survival of patients with carcinoma of the gastric cardia.

Predictors of in-hospital mortality amongst octogenarians undergoing emergency general surgery: a retrospective cohort study.

PubMed

Wilson, Iain; Paul Barrett, Michael; Sinha, Ashish; Chan, Shirley

2014-11-01

Elderly patients are often judged to be fit for emergency surgery based on age alone. This study identified risk factors predictive of in-hospital mortality amongst octogenarians undergoing emergency general surgery. A retrospective review of octogenarians undergoing emergency general surgery over 3 years was performed. Parametric survival analysis using Cox multivariate regression model was used to identify risk factors predictive of in-hospital mortality. Hazard ratios (HR) and corresponding 95% confidence interval were calculated. Seventy-three patients with a median age of 84 years were identified. Twenty-eight (38%) patients died post-operatively. Multivariate analysis identified ASA grade (ASA 5 HR 23.4 95% CI 2.38-230, p = 0.007) and chronic obstructive pulmonary disease (COPD) (HR 3.35 95% CI 1.15-9.69, p = 0.026) to be the only significant predictors of in-hospital mortality. Identification of high risk surgical patients should be based on physiological fitness for surgery rather than chronological age. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Multivariate Models for Normal and Binary Responses in Intervention Studies

ERIC Educational Resources Information Center

Pituch, Keenan A.; Whittaker, Tiffany A.; Chang, Wanchen

2016-01-01

Use of multivariate analysis (e.g., multivariate analysis of variance) is common when normally distributed outcomes are collected in intervention research. However, when mixed responses--a set of normal and binary outcomes--are collected, standard multivariate analyses are no longer suitable. While mixed responses are often obtained in…

Delirium superimposed on dementia: defining disease states and course from longitudinal measurements of a multivariate index using latent class analysis and hidden Markov chains.

PubMed

Ciampi, Antonio; Dyachenko, Alina; Cole, Martin; McCusker, Jane

2011-12-01

The study of mental disorders in the elderly presents substantial challenges due to population heterogeneity, coexistence of different mental disorders, and diagnostic uncertainty. While reliable tools have been developed to collect relevant data, new approaches to study design and analysis are needed. We focus on a new analytic approach. Our framework is based on latent class analysis and hidden Markov chains. From repeated measurements of a multivariate disease index, we extract the notion of underlying state of a patient at a time point. The course of the disorder is then a sequence of transitions among states. States and transitions are not observable; however, the probability of being in a state at a time point, and the transition probabilities from one state to another over time can be estimated. Data from 444 patients with and without diagnosis of delirium and dementia were available from a previous study. The Delirium Index was measured at diagnosis, and at 2 and 6 months from diagnosis. Four latent classes were identified: fairly healthy, moderately ill, clearly sick, and very sick. Dementia and delirium could not be separated on the basis of these data alone. Indeed, as the probability of delirium increased, so did the probability of decline of mental functions. Eight most probable courses were identified, including good and poor stable courses, and courses exhibiting various patterns of improvement. Latent class analysis and hidden Markov chains offer a promising tool for studying mental disorders in the elderly. Its use may show its full potential as new data become available.

Biometrics from the carbon isotope ratio analysis of amino acids in human hair.

PubMed

Jackson, Glen P; An, Yan; Konstantynova, Kateryna I; Rashaid, Ayat H B

2015-01-01

This study compares and contrasts the ability to classify individuals into different grouping factors through either bulk isotope ratio analysis or amino-acid-specific isotope ratio analysis of human hair. Using LC-IRMS, we measured the isotope ratios of 14 amino acids in hair proteins independently, and leucine/isoleucine as a co-eluting pair, to provide 15 variables for classification. Multivariate analysis confirmed that the essential amino acids and non-essential amino acids were mostly independent variables in the classification rules, thereby enabling the separation of dietary factors of isotope intake from intrinsic or phenotypic factors of isotope fractionation. Multivariate analysis revealed at least two potential sources of non-dietary factors influencing the carbon isotope ratio values of the amino acids in human hair: body mass index (BMI) and age. These results provide evidence that compound-specific isotope ratio analysis has the potential to go beyond region-of-origin or geospatial movements of individuals-obtainable through bulk isotope measurements-to the provision of physical and characteristic traits about the individuals, such as age and BMI. Further development and refinement, for example to genetic, metabolic, disease and hormonal factors could ultimately be of great assistance in forensic and clinical casework. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Magnitude and Correlates of Anemia in Elderly Women of a Resettlement Colony of Delhi.

PubMed

Singh, Tulika; Nagesh, S; Ray, T K

2018-01-01

Anemia of any degree contributes significantly to morbidity and mortality and has a significant effect on the quality of life of elderly women. Despite its clinical importance, anemia in the elderly women is underrecognized. The objective of this study was to assess the magnitude and correlates of anemia in elderly women of a resettlement colony of Delhi. A community-based, cross-sectional study for the duration of 1 year was conducted among 512 geriatric women (≥60 years). Demographic characteristics, dietary assessment, and behavioral risk factors were determined by interview, and the participants underwent physical examination followed by hemoglobin estimation by HemoCue. Anemia was defined using the WHO criteria of hemoglobin <12 g/dl. Chi-square test was employed to study the association between sociodemographic factors and anemia followed by multivariate regression analysis. The prevalence of anemia was 79.9% according to the WHO criteria of hemoglobin <12 g/dl in females. Age, education, marital status, financial dependence, diagnosed chronic disease, diet, calorie intake, history of worm infestation, and body mass index (BMI) were significantly associated with anemia on univariate analysis. In multivariate analysis, age, marital status, financial dependence, diagnosed chronic disease, diet, calorie intake, and BMI were significant explanatory variables for anemia. Our study points out high prevalence of and some of the major factors associated with anemia in elderly women. The need of the hour is to include our elderly women under the gamut of National Anemia Prophylaxis Program.

Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

PubMed Central

Yokoyama, Miyuki; Otaki, Yoichiro; Takahashi, Hiroki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Shibata, Yoko; Daimon, Makoto; Kayama, Takamasa; Kubota, Isao

2016-01-01

Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST) to alanine aminotransferase (ALT). However, the association of AST/ALT ratio with brain natriuretic peptide (BNP) levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL). There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile) was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality. PMID:27872510

Prediction of Postoperative Mortality in Liver Transplantation in the Era of MELD-Based Liver Allocation: A Multivariate Analysis

PubMed Central

Schultze, Daniel; Hillebrand, Norbert; Hinz, Ulf; Büchler, Markus W.; Schemmer, Peter

2014-01-01

Background and Aims Liver transplantation is the only curative treatment for end-stage liver disease. While waiting list mortality can be predicted by the MELD-score, reliable scoring systems for the postoperative period do not exist. This study's objective was to identify risk factors that contribute to postoperative mortality. Methods Between December 2006 and March 2011, 429 patients underwent liver transplantation in our department. Risk factors for postoperative mortality in 266 consecutive liver transplantations were identified using univariate and multivariate analyses. Patients who were <18 years, HU-listings, and split-, living related, combined or re-transplantations were excluded from the analysis. The correlation between number of risk factors and mortality was analyzed. Results A labMELD ≥20, female sex, coronary heart disease, donor risk index >1.5 and donor Na+>145 mmol/L were identified to be independent predictive factors for postoperative mortality. With increasing number of these risk-factors, postoperative 90-day and 1-year mortality increased (0–1: 0 and 0%; 2: 2.9 and 17.4%; 3: 5.6 and 16.8%; 4: 22.2 and 33.3%; 5–6: 60.9 and 66.2%). Conclusions In this analysis, a simple score was derived that adequately identified patients at risk after liver transplantation. Opening a discussion on the inclusion of these parameters in the process of organ allocation may be a worthwhile venture. PMID:24905210

Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea.

PubMed

Zulu, Isaac; Hassan, Ghaniah; Njobvu R N, Lungowe; Dhaliwal, Winnie; Sianongo, Sandie; Kelly, Paul

2008-11-13

Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality. Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-gamma and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up. Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-gamma, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis. High serum concentrations of TNFR p55, IFN-gamma, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.

Impact of Virtual Touch Quantification in Acoustic Radiation Force Impulse for Skeletal Muscle Mass Loss in Chronic Liver Diseases

PubMed Central

Nishikawa, Hiroki; Nishimura, Takashi; Enomoto, Hirayuki; Iwata, Yoshinori; Ishii, Akio; Miyamoto, Yuho; Ishii, Noriko; Yuri, Yukihisa; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Yoh, Kazunori; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Nishiguchi, Shuhei; Iijima, Hiroko

2017-01-01

Background and aims: We sought to clarify the relationship between virtual touch quantification (VTQ) in acoustic radiation force impulse and skeletal muscle mass as assessed by bio-electronic impedance analysis in patients with chronic liver diseases (CLDs, n = 468, 222 males and 246 females, median age = 62 years). Patients and methods: Decreased skeletal muscle index (D-SMI) was defined as skeletal muscle index (SMI) <7.0 kg/m2 for males and as SMI <5.7 kg/m2 for females, according to the recommendations in current Japanese guidelines. We examined the correlation between SMI and VTQ levels and investigated factors linked to D-SMI in the univariate and multivariate analyses. The area under the receiver operating curve (AUROC) for the presence of D-SMI was also calculated. Results: In patients with D-SMI, the median VTQ level was 1.64 meters/second (m/s) (range, 0.93–4.32 m/s), while in patients without D-SMI, the median VTQ level was 1.11 m/s (range, 0.67–4.09 m/s) (p < 0.0001). In the multivariate analysis, higher VTQ was found to be an independent predictor linked to the presence of D-SMI (p < 0.0001). In receiver operating characteristic analysis, body mass index had the highest AUROC (0.805), followed by age (0.721) and VTQ (0.706). Conclusion: VTQ levels can be useful for predicting D-SMI in patients with CLDs. PMID:28621757

Sociodemographic factors and health conditions associated with the resilience of people with chronic diseases: a cross sectional study 1

PubMed Central

Böell, Julia Estela Willrich; da Silva, Denise Maria Guerreiro Vieira; Hegadoren, Kathleen Mary

2016-01-01

ABSTRACT Objective: to investigate the association between resilience and sociodemographic variables and the health of people with chronic kidney disease and / or type 2 diabetes mellitus. Method: a cross-sectional observational study performed with 603 people with chronic kidney disease and / or type 2 diabetes mellitus. A tool to collect socio-demographic and health data and the Resilience Scale developed by Connor and Davidson were applied. A descriptive and multivariate analysis was performed. Results: the study participants had on average 61 years old (SD= 13.2), with a stable union (52.24%), religion (96.7%), retired (49.09%), with primary education (65%) and income up to three minimum wages. Participants with kidney disease showed less resilience than people with diabetes. Conclusion: the type of chronic illness, disease duration, body mass index and religious beliefs influenced the resilience of the study participants. PMID:27598377

Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival.

PubMed

Heitz, F; Rochon, J; Harter, P; Lueck, H-J; Fisseler-Eckhoff, A; Barinoff, J; Traut, A; Lorenz-Salehi, F; du Bois, A

2011-07-01

Survival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. Exploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008 using cumulative incidences and Fine and Grays' multivariable regression analyses. After a median follow-up of 4.0 years, 66 patients (10.5%) developed CM. The estimated probability for CM was 5%, 12% and 15% at 1, 5 and 10 years; in contrast, the probability of death without CM was 21%, 61% and 76%, respectively. A small tumor size, ER status, ductal histology, lung and lymph node metastases, human epidermal growth factor receptor 2 positive (HER2+) tumors, younger age and M0 were associated with CM in univariate analyses, the latter three being risk factors in the multivariable model. Survival was shortened in patient developing CM (24.0 months) compared with patients with no CM (33.6 months) in the course of MBC. Young patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PubMed

Koontz, Bridget F; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W Robert

2012-01-01

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Resistance Training Exercise Program for Intervention to Enhance Gait Function in Elderly Chronically Ill Patients: Multivariate Multiscale Entropy for Center of Pressure Signal Analysis

PubMed Central

Jiang, Bernard C.

2014-01-01

Falls are unpredictable accidents, and the resulting injuries can be serious in the elderly, particularly those with chronic diseases. Regular exercise is recommended to prevent and treat hypertension and other chronic diseases by reducing clinical blood pressure. The “complexity index” (CI), based on multiscale entropy (MSE) algorithm, has been applied in recent studies to show a person's adaptability to intrinsic and external perturbations and widely used measure of postural sway or stability. The multivariate multiscale entropy (MMSE) was advanced algorithm used to calculate the complexity index (CI) values of the center of pressure (COP) data. In this study, we applied the MSE & MMSE to analyze gait function of 24 elderly, chronically ill patients (44% female; 56% male; mean age, 67.56 ± 10.70 years) with either cardiovascular disease, diabetes mellitus, or osteoporosis. After a 12-week training program, postural stability measurements showed significant improvements. Our results showed beneficial effects of resistance training, which can be used to improve postural stability in the elderly and indicated that MMSE algorithms to calculate CI of the COP data were superior to the multiscale entropy (MSE) algorithm to identify the sense of balance in the elderly. PMID:25295070

Colorectal cancers in ulcerative colitis from a low-prevalence area for colon cancer

PubMed Central

Desai, Devendra; Shah, Sudeep; Deshmukh, Abhijit; Abraham, Philip; Joshi, Anand; Gupta, Tarun; Deshpande, Ramesh; Khandagale, Varun; George, Siji

2015-01-01

AIM: To determine the incidence and risk factors for colorectal cancer (CRC) in patients with ulcerative colitis from a low prevalence region for CRC. METHODS: Our prospective database yielded a cohort of 430 patients [age: 44 ± 14.6 years; 248 men (57.7%)] with ulcerative colitis (median disease duration 6, range: 1-39 years) for analysis. Of these, 131 (30.5%) had left-sided colitis and 159 (37%) extensive colitis. Patients with histologically confirmed CRC within the segment with colitis were compared with those without CRC, to determine the risk factors for the development of CRC. RESULTS: Twelve patients (2.8%) developed CRC. The overall incidence density was 3.56/1000 patient-years of disease - 3/1000 in the first 10 years, 3.3/1000 at 10 to 20 years, and 7/1000 at > 20 years. Three of our 12 patients developed CRC within 8 years of disease onset. On univariate analysis, extensive colitis, longer duration of disease, and poor control of disease were associated with development of CRC. On multivariate analysis, duration of disease and extent of colitis remained significant. CONCLUSION: CRC occurred in 2.8% of patients with ulcerative colitis in our population - an incidence density similar to that in Western countries in spite of a low overall prevalence of colon cancer in our population. The risk increased with extent and duration of disease. PMID:25834332

Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas

PubMed Central

Kai, Keita; Komukai, Sho; Koga, Hiroki; Yamaji, Koutaro; Ide, Takao; Kawaguchi, Atsushi; Aishima, Shinichi; Noshiro, Hirokazu

2018-01-01

AIM To investigate the association between smoking habits and surgical outcomes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients. METHODS We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups’ clinicopathological features and surgical outcomes, i.e., disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients. RESULTS The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS (P = 0.0039) and DSS (P = 0.0416). In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS, or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status. CONCLUSION A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes. PMID:29358882

Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas.

PubMed

Kai, Keita; Komukai, Sho; Koga, Hiroki; Yamaji, Koutaro; Ide, Takao; Kawaguchi, Atsushi; Aishima, Shinichi; Noshiro, Hirokazu

2018-01-07

To investigate the association between smoking habits and surgical outcomes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients. We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups' clinicopathological features and surgical outcomes, i.e ., disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients. The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS ( P = 0.0039) and DSS ( P = 0.0416). In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS, or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status. A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PubMed

van Dalen, A; Favier, J; Hallensleben, E; Burges, A; Stieber, P; de Bruijn, H W A; Fink, D; Ferrero, A; McGing, P; Harlozinska, A; Kainz, Ch; Markowska, J; Molina, R; Sturgeon, C; Bowman, A; Einarsson, R; Goike, H

2009-01-01

To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner

2007-03-15

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, andmore » delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.« less

Brain regions with abnormal network properties in severe epilepsy of Lennox-Gastaut phenotype: Multivariate analysis of task-free fMRI.

PubMed

Pedersen, Mangor; Curwood, Evan K; Archer, John S; Abbott, David F; Jackson, Graeme D

2015-11-01

Lennox-Gastaut syndrome, and the similar but less tightly defined Lennox-Gastaut phenotype, describe patients with severe epilepsy, generalized epileptic discharges, and variable intellectual disability. Our previous functional neuroimaging studies suggest that abnormal diffuse association network activity underlies the epileptic discharges of this clinical phenotype. Herein we use a data-driven multivariate approach to determine the spatial changes in local and global networks of patients with severe epilepsy of the Lennox-Gastaut phenotype. We studied 9 adult patients and 14 controls. In 20 min of task-free blood oxygen level-dependent functional magnetic resonance imaging data, two metrics of functional connectivity were studied: Regional homogeneity or local connectivity, a measure of concordance between each voxel to a focal cluster of adjacent voxels; and eigenvector centrality, a global connectivity estimate designed to detect important neural hubs. Multivariate pattern analysis of these data in a machine-learning framework was used to identify spatial features that classified disease subjects. Multivariate pattern analysis was 95.7% accurate in classifying subjects for both local and global connectivity measures (22/23 subjects correctly classified). Maximal discriminating features were the following: increased local connectivity in frontoinsular and intraparietal areas; increased global connectivity in posterior association areas; decreased local connectivity in sensory (visual and auditory) and medial frontal cortices; and decreased global connectivity in the cingulate cortex, striatum, hippocampus, and pons. Using a data-driven analysis method in task-free functional magnetic resonance imaging, we show increased connectivity in critical areas of association cortex and decreased connectivity in primary cortex. This supports previous findings of a critical role for these association cortical regions as a final common pathway in generating the Lennox-Gastaut phenotype. Abnormal function of these areas is likely to be important in explaining the intellectual problems characteristic of this disorder. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Psychotropic medication use among patients with celiac disease.

PubMed

Zylberberg, Haley M; Ludvigsson, Jonas F; Green, Peter H R; Lebwohl, Benjamin

2018-03-27

Celiac disease is a multi-system disorder with manifestations that may result in psychiatric disorders. We assessed the prevalence of medication use to treat psychiatric disorders in celiac disease patients. We conducted a cross-sectional study of patients undergoing esophagogastroduodenoscopy over 9-years at a celiac disease referral center. We compared the prevalence of psychotropic medication use among celiac disease patients (n = 1293) to a control group (n = 1401) with abdominal pain or reflux. Among all patients the mean age was 48.4 years, most were female (69.5%), and 22.7% used any psychotropic medication. There was no difference between overall psychotropic medication use among celiac disease patients and controls (23.9% vs 21.8%, OR 1.16; 95% CI 0.96-1.39, p = 0.12). However, those with celiac disease were more likely to use antidepressants on univariate (16.4% vs 13.4%, p = 0.03) and multivariate analysis (OR 1.28; 95% CI 1.03-1.59; p = 0.03). Use of psychotropic medications was not associated with disease duration or mode of presentation of celiac disease. Celiac disease patients use psychotropic medications at similar rates as those with other gastrointestinal diseases, though subgroup analysis suggests they may use more antidepressants. Future studies should investigate whether celiac disease is associated with mood disorders that are not treated with medications.

Deconstructing multivariate decoding for the study of brain function.

PubMed

Hebart, Martin N; Baker, Chris I

2017-08-04

Multivariate decoding methods were developed originally as tools to enable accurate predictions in real-world applications. The realization that these methods can also be employed to study brain function has led to their widespread adoption in the neurosciences. However, prior to the rise of multivariate decoding, the study of brain function was firmly embedded in a statistical philosophy grounded on univariate methods of data analysis. In this way, multivariate decoding for brain interpretation grew out of two established frameworks: multivariate decoding for predictions in real-world applications, and classical univariate analysis based on the study and interpretation of brain activation. We argue that this led to two confusions, one reflecting a mixture of multivariate decoding for prediction or interpretation, and the other a mixture of the conceptual and statistical philosophies underlying multivariate decoding and classical univariate analysis. Here we attempt to systematically disambiguate multivariate decoding for the study of brain function from the frameworks it grew out of. After elaborating these confusions and their consequences, we describe six, often unappreciated, differences between classical univariate analysis and multivariate decoding. We then focus on how the common interpretation of what is signal and noise changes in multivariate decoding. Finally, we use four examples to illustrate where these confusions may impact the interpretation of neuroimaging data. We conclude with a discussion of potential strategies to help resolve these confusions in interpreting multivariate decoding results, including the potential departure from multivariate decoding methods for the study of brain function. Copyright © 2017. Published by Elsevier Inc.

The tobacco paradox in acute coronary syndrome. The prior cessation of smoking as a marker of a better short-term prognosis.

PubMed

Bastos-Amador, P; Almendro-Delia, M; Muñoz-Calero, B; Blanco-Ponce, E; Recio-Mayoral, A; Reina-Toral, A; Cruz-Fernandez, J M; García-Alcántara, A; Hidalgo-Urbano, R; García-Rubira, J C

2016-01-01

The tobacco paradox is a phenomenon insufficiently explained by previous studies. This study analyses the prognostic role of prior or active smoking in patients with acute coronary syndrome. We obtained data from the ARIAM registry, between 2001 and 2012. The study included 42,827 patients with acute coronary syndrome (mean age, 65±13 years; 26.4% women). The influence of smoking and that of being an ex-smoker on mortality was analysed using a multivariate analysis. The smokers were younger, were more often men, had less diabetes, hypertension and prior history of heart failure, stroke, arrhythmia and renal failure and more frequently had ST-elevation and a family history of smoking. The ex-smokers had more dyslipidaemia and history of angina, myocardial infarction, ischemic heart disease, peripheral vasculopathy and chronic bronchial disease. Smokers and ex-smokers less frequently developed cardiogenic shock (smokers 4.2%, ex-smokers 4.7% and nonsmokers 6.9%, P<.001). Hospital mortality was 7.8% for the nonsmokers, 4.9% for the ex-smokers and 3.1% for the smokers (P<.001). In the multivariate analysis, the smoker factor lost its influence in the prognosis (-0.26%, p=.52 using an inverse probability calculation; and+0.26%, P=.691 using a propensity analysis). However, the exsmoker factor showed a significant reduction in mortality in both tests (-2.4% in the inverse probability analysis, P<.001; and -1.5% in the propensity analysis, P=.005). The tobacco paradox is a finding that could be explained by other prognostic factors. Smoking cessation prior to hospitalization for acute coronary syndrome is associated with a better prognosis. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Tumour location within the breast: Does tumour site have prognostic ability?

PubMed

Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

2015-01-01

Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P < 0.05. Of the 980 patients with defined tumour location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P < 0.001), metastatic lymph nodes (P < 0.001), and mortality (P = 0.011). After multivariate analysis, only tumour size and lymph node status remained significantly associated with survival. Evaluation of tumour location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

Identifying HIV associated neurocognitive disorder using large-scale Granger causality analysis on resting-state functional MRI

NASA Astrophysics Data System (ADS)

DSouza, Adora M.; Abidin, Anas Z.; Leistritz, Lutz; Wismüller, Axel

2017-02-01

We investigate the applicability of large-scale Granger Causality (lsGC) for extracting a measure of multivariate information flow between pairs of regional brain activities from resting-state functional MRI (fMRI) and test the effectiveness of these measures for predicting a disease state. Such pairwise multivariate measures of interaction provide high-dimensional representations of connectivity profiles for each subject and are used in a machine learning task to distinguish between healthy controls and individuals presenting with symptoms of HIV Associated Neurocognitive Disorder (HAND). Cognitive impairment in several domains can occur as a result of HIV infection of the central nervous system. The current paradigm for assessing such impairment is through neuropsychological testing. With fMRI data analysis, we aim at non-invasively capturing differences in brain connectivity patterns between healthy subjects and subjects presenting with symptoms of HAND. To classify the extracted interaction patterns among brain regions, we use a prototype-based learning algorithm called Generalized Matrix Learning Vector Quantization (GMLVQ). Our approach to characterize connectivity using lsGC followed by GMLVQ for subsequent classification yields good prediction results with an accuracy of 87% and an area under the ROC curve (AUC) of up to 0.90. We obtain a statistically significant improvement (p<0.01) over a conventional Granger causality approach (accuracy = 0.76, AUC = 0.74). High accuracy and AUC values using our multivariate method to connectivity analysis suggests that our approach is able to better capture changes in interaction patterns between different brain regions when compared to conventional Granger causality analysis known from the literature.

Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease.

PubMed

Pereira, Andreia; Mendonca, Maria Isabel; Sousa, Ana Célia; Borges, Sofia; Freitas, Sónia; Henriques, Eva; Rodrigues, Mariana; Freitas, Ana Isabel; Guerra, Graça; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Palma Dos Reis, Roberto

2017-06-01

Several genetic risk scores (GRS) have been associated with cardiovascular disease; their role, however, in survival from proven coronary artery disease (CAD) have yielded conflicting results. The objective of this study was to evaluate long-term cardiovascular mortality according to the genetic risk score in a Southern European population with CAD. A cohort of 1464 CAD patients with angiographic proven CAD were followed up prospectively for up to 58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide polymorphisms previously associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming codominance and categorised using the median (=26). Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan-Meier survival curves compared high vs low GRS using log-rank test. C-index was done for our population, as a measure of discrimination in survival analysis model. During a mean follow-up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes. High GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with Cox regression model adjusted for 8 variables showed that high GRS, dyslipidemia, diabetes and 3-vessel disease were independent risk factors for cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004; HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6; P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease, stable angina and dual antiplatelet therapy. Besides the classical risk factors management, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be dirsected to gene targets with proven value in cardiovascular survival. © 2017 John Wiley & Sons Ltd.

Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still's disease: A multicenter retrospective study.

PubMed

Kirino, Yohei; Kawaguchi, Yasushi; Tada, Yoshifumi; Tsukamoto, Hiroshi; Ota, Toshiyuki; Iwamoto, Masahiro; Takahashi, Hiroki; Nagasawa, Kohei; Takei, Shuji; Horiuchi, Takahiko; Ichida, Hisae; Minota, Seiji; Ueda, Atsuhisa; Ohta, Akihide; Ishigatsubo, Yoshiaki

2018-01-11

Heme oxygenase (HO)-1 is a heme-degrading enzyme highly expressed in monocyte/macrophage, serum levels of which may be promising biomarker for adult-onset Still's disease (AOSD). We here report data on the use of serum ferritin and HO-1 levels in AOSD. Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD patients. Three independent experts judged whether the patients were definite AOSD depending on the clinical information. These 91 'definite AOSD' patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. Serum ferritin and HO-1 levels were measured using ELISA. Associations between clinical symptoms, serum ferritin, and HO-1 were explored. Multivariate regression analysis was performed to identify independent variables associated with definite AOSD diagnosis. Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia. Receiver operating characteristic analysis identified optimal levels of serum ferritin (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p = .013), suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status. Multivariate analysis identified neutrophilia, RF/ANA negativity, sore throat, and elevated serum HO-1 as independent variables associated with AOSD diagnosis. We confirmed that serum ferritin and HO-1 serve as highly specific and sensitive biomarkers for AOSD. A future prospective study with large sample size is necessary to determine whether these biomarkers could be included in Yamaguchi's Criteria.

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma

PubMed Central

Luo, Yihuan; Zhang, Xin; Mo, Meile; Tan, Zhong; Huang, Lanshan; Zhou, Hong; Wang, Chunqin; Wei, Fanglin; Qiu, Xiaohui; He, Rongquan; Chen, Gang

2016-01-01

Abstract Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623–4.127, P < 0.001), 2.697 (95%CI: 1.874–3.883, P < 0.001), 2.649 (95%CI: 1.632–4.300, P < 0.001), 3.506 (95%CI: 2.231–5.508, P < 0.001), and 1.792 (95%CI: 1.409–2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343–2.597, P < 0.001), 2.626 (95%CI: 2.089–3.301, P < 0.001), 1.104 (95%CI: 1.008–1.209, P = 0.032), 1.518 (95%CI: 1.299–1.773, P < 0.001), and 1.294 (95%CI: 1.203–1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P < 0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P < 0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P < 0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05). The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the meta-analyses of multivariate analysis. PMID:27082587

Multivariate meta-analysis: Potential and promise

PubMed Central

Jackson, Dan; Riley, Richard; White, Ian R

2011-01-01

The multivariate random effects model is a generalization of the standard univariate model. Multivariate meta-analysis is becoming more commonly used and the techniques and related computer software, although continually under development, are now in place. In order to raise awareness of the multivariate methods, and discuss their advantages and disadvantages, we organized a one day ‘Multivariate meta-analysis’ event at the Royal Statistical Society. In addition to disseminating the most recent developments, we also received an abundance of comments, concerns, insights, critiques and encouragement. This article provides a balanced account of the day's discourse. By giving others the opportunity to respond to our assessment, we hope to ensure that the various view points and opinions are aired before multivariate meta-analysis simply becomes another widely used de facto method without any proper consideration of it by the medical statistics community. We describe the areas of application that multivariate meta-analysis has found, the methods available, the difficulties typically encountered and the arguments for and against the multivariate methods, using four representative but contrasting examples. We conclude that the multivariate methods can be useful, and in particular can provide estimates with better statistical properties, but also that these benefits come at the price of making more assumptions which do not result in better inference in every case. Although there is evidence that multivariate meta-analysis has considerable potential, it must be even more carefully applied than its univariate counterpart in practice. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21268052

Adherence rates and health care costs in Crohn's disease patients receiving certolizumab pegol with and without home health nurse assistance: results from a retrospective analysis of patient claims and home health nurse data.

PubMed

Wolf, Douglas C; Jaganathan, Srihari; Burudpakdee, Chakkarin; Seetasith, Arpamas; Low, Robert; Lee, Edward; Gucky, Jay; Yassine, Mohamed; Schwartz, David A

2018-01-01

Patient support programs have a positive effect on adherence to therapy. Certolizumab pegol (CZP) is a tumor necrosis factor antagonist for the treatment of Crohn's disease. To assess, using real-world claims data, whether home health nurse assistance had an effect on patients' adherence to CZP and to measure its impact on health care use and costs. A retrospective analysis of medical and pharmacy claims data from the IQVIA Real-World Data Adjudicated Claims Database was conducted using data from January 1, 2007 through September 30, 2015. CZP patients with Crohn's disease were eligible to receive self-administration instructions from a nurse or nurse-administered CZP injections, or both. These services were provided by CIMplicity ® , a home health nurse program sponsored by UCB Pharma. Cohorts were based on patients with and without nurse assistance and were matched based on gender and categorical age. Adherence to CZP was determined using the medication possession ratio (MPR) and proportion of days covered (PDC). A Kaplan-Meier analysis was performed to compare time to discontinuation of CZP between the two cohorts. Multivariate regression analyses were performed, adjusting for additional covariates to compare the effect of CZP with and without nurse assistance on hospitalization and total health care costs. Patients with at least 12 months of continuous enrollment post-index date were evaluated for adherence to CZP (n=276 in each cohort). The mean and median PDC and MPR values were higher with nurse assistance than without. Time to discontinuation was significantly longer in patients who received CZP with nurse assistance than without ( P =0.0004). Results from the multivariate analyses showed a significant reduction in all-cause hospitalization (-55.8%; P =0.0026) and total health care costs (-14.3%; P =0.0045) with nurse assistance. This analysis suggests that home health nurse assistance increases adherence to CZP and reduces health care costs in patients with Crohn's disease.

Analysis of multivariate longitudinal kidney function outcomes using generalized linear mixed models.

PubMed

Jaffa, Miran A; Gebregziabher, Mulugeta; Jaffa, Ayad A

2015-06-14

Renal transplant patients are mandated to have continuous assessment of their kidney function over time to monitor disease progression determined by changes in blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). Multivariate analysis of these outcomes that aims at identifying the differential factors that affect disease progression is of great clinical significance. Thus our study aims at demonstrating the application of different joint modeling approaches with random coefficients on a cohort of renal transplant patients and presenting a comparison of their performance through a pseudo-simulation study. The objective of this comparison is to identify the model with best performance and to determine whether accuracy compensates for complexity in the different multivariate joint models. We propose a novel application of multivariate Generalized Linear Mixed Models (mGLMM) to analyze multiple longitudinal kidney function outcomes collected over 3 years on a cohort of 110 renal transplantation patients. The correlated outcomes BUN, Cr, and eGFR and the effect of various covariates such patient's gender, age and race on these markers was determined holistically using different mGLMMs. The performance of the various mGLMMs that encompass shared random intercept (SHRI), shared random intercept and slope (SHRIS), separate random intercept (SPRI) and separate random intercept and slope (SPRIS) was assessed to identify the one that has the best fit and most accurate estimates. A bootstrap pseudo-simulation study was conducted to gauge the tradeoff between the complexity and accuracy of the models. Accuracy was determined using two measures; the mean of the differences between the estimates of the bootstrapped datasets and the true beta obtained from the application of each model on the renal dataset, and the mean of the square of these differences. The results showed that SPRI provided most accurate estimates and did not exhibit any computational or convergence problem. Higher accuracy was demonstrated when the level of complexity increased from shared random coefficient models to the separate random coefficient alternatives with SPRI showing to have the best fit and most accurate estimates.

The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus.

PubMed

Taraborelli, M; Lazzaroni, M G; Martinazzi, N; Fredi, M; Cavazzana, I; Franceschini, F; Tincani, A

2016-12-16

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM >99th percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher's exact test for categorical variables and Student's t or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS.

Abdominal aortic aneurysm. Prevalence and associated risk factors in a population of patients hospitalised in Internal Medicine.

PubMed

Belloch García, S L

2018-05-29

To determine the prevalence of previously undiagnosed abdominal aortic aneurysm (AAA) in patients hospitalised in a department of internal medicine, as well as the associated risk factors. An observational, cross-sectional, single-centre, randomised study was conducted on 241 patients hospitalised in Internal Medicine. The patients were older than 50 years, had no previous diagnosis of AAA and underwent clinical ultrasonography. The dependent variable was the presence or absence of an aneurysm. The independent variables were age, sex, cardiovascular risk factors, cardiovascular disease, renal function, ankle brachial index (ABI), family history (first degree) of AAA or of early ischaemic heart disease. A bivariate and multivariate analysis was conducted in the statistical analysis. The prevalence of AAA was 2.9% (95% CI: 0.8-5). The cases were confirmed through ultrasonography or computed tomography by the Department of Radiology. All patients were men with a history of smoking and with an age≥65 years. The bivariate analysis found an association between being male (OR, 9.39), smoking (OR, 13.08), ischaemic heart disease (OR, 5.6; 95% CI: 1.21-25.91; P<.05) and ABI<0.9 (OR, 12.50; 95% CI: 2.34-66.77; P<.05). In the multivariate analysis, the independently associated variable was an ABI<0.9 (OR, 10.758; 95% CI: 1.968-58.815; P=.006). The prevalence of undiagnosed AAA in patients older than 50 years hospitalised in internal medicine was 2.9%. The data lead us to recommend AAA screening for this population of male patients with a history of smoking and an ABI<0.9. Clinical ultrasonography enables this screening in a reliable manner. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Proton pump inhibitor use and recurrent Clostridium difficile-associated disease: a case-control analysis matched by propensity score.

PubMed

Kim, Yong Gil; Graham, David Y; Jang, Byung Ik

2012-01-01

Clostridium difficile has been increasingly diagnosed in hospitalized patients. An association between proton pump inhibitors (PPIs) use and Clostridium difficile-associated disease (CDAD) and between recurrent CDAD has been suggested. The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD. This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center, seen from January 2004 to December 2008. C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool. Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score. Recurrent CDAD developed in 28 (14.1%) of the 198 patients with diarrhea and positive C. difficile stool toxin assays. Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy (concomitant with the treatment or after or both), poor response to therapy with metronidazole or vancomycin, and recent gastrointestinal surgery were risk factors for recurrent CDAD. We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD. Among the matched patients only PPI use was associated with recurrent CDAD (ie, 47.6% vs. 4.8%, P=0.004 for recurrent vs. nonrecurrent CDAD, respectively). Among the matched patient groups, only PPI therapy was associated with recurrent CDAD. Prospective studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile-associated diarrhea.

Working after a metastatic cancer diagnosis: Factors affecting employment in the metastatic setting from ECOG-ACRIN's Symptom Outcomes and Practice Patterns study.

PubMed

Tevaarwerk, Amye J; Lee, Ju-Whei; Terhaar, Abigail; Sesto, Mary E; Smith, Mary Lou; Cleeland, Charles S; Fisch, Michael J

2016-02-01

Improved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. A better understanding of how metastatic cancer affects employment is a necessary step toward the development of tools for assisting survivors in this important realm. The ECOG-ACRIN Symptom Outcomes and Practice Patterns study was analyzed to investigate what factors were associated with the employment of 680 metastatic cancer patients. Univariate and multivariate logistic regression analyses were conducted to compare patients stably working with patients no longer working. There were 668 metastatic working-age participants in the analysis: 236 (35%) worked full- or part-time, whereas 302 (45%) had stopped working because of illness. Overall, 58% reported some change in employment due to illness. A better performance status and non-Hispanic white ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis in the multivariate analysis. The disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. A significant percentage of the metastatic patients remained employed; increased symptom burden was associated with a change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working if this is desired. Improvements in symptom control and strategies developed to help address workplace difficulties have promise for improving this aspect of survivorship. © 2015 American Cancer Society.

Antibody response to influenza vaccination in nursing home residents and healthcare workers during four successive seasons in Niigata, Japan.

PubMed

Sato, Mizuho; Saito, Reiko; Tanabe, Naohito; Nishikawa, Makoto; Sasaki, Asami; Gejyo, Fumitake; Suzuki, Hiroshi

2005-11-01

To evaluate the antibody response to influenza vaccines in nursing home residents and healthcare workers (HCWs) and its relation to residents' functional and chronic disease status during four successive seasons. Before-after study. Nine nursing homes during the 1998-1999 season and two during the 1999-2000, 2000-2001, and 2001-2002 seasons. Two hundred fifty-nine residents and 79 HCWs during the 1998-1999 season; 180 and 71, respectively, during the 1999-2000 season; 162 and 71, respectively, during the 2000-2001 season; and 153 and 79, respectively, during the 2001-2002 season. Multivariate analysis indicated that the mean fold increase in the geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies and the response rate (the proportion of vaccinees resulting in a significant, at least fourfold increase in antibody titer) were good and no significant differences occurred for almost all strains in both residents and HCWs. The GMTs of HI antibodies and the protection rate (the proportion of participants with HI antibody titers > or = 40) were increased in both residents and HCWs, but were significantly lower for almost all strains in residents than in HCWs. Furthermore, multivariate analysis indicated that subdivision of residents into three groups by level of daily activities and into four groups according to underlying diseases revealed only minor differences in immune responses. Antibody responses to the influenza vaccine were lower in residents than in HCWs. However, residents showed similar antibody responses regardless of their level of daily activity or underlying diseases.

First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012.

PubMed

Bacigalupo, Andrea; Oneto, Rosi; Schrezenmeier, Hubert; Hochsmann, Britta; Dufour, Carlo; Kojima, Seiji; Zhu, Xiaofan; Chen, Xiaojuan; Issaragrisil, Surapol; Chuncharunee, Suporn; Jeong, Dae Chul; Giammarco, Sabrina; Van Lint, Maria Teresa; Zheng, Yizhou; Vallejo, Carlos

2018-05-01

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival. © 2018 Wiley Periodicals, Inc.

Desmoid-type fibromatosis: a front-line conservative approach to select patients for surgical treatment.

PubMed

Fiore, Marco; Rimareix, Françoise; Mariani, Luigi; Domont, Julien; Collini, Paola; Le Péchoux, Cecile; Casali, Paolo G; Le Cesne, Axel; Gronchi, Alessandro; Bonvalot, Sylvie

2009-09-01

Surgery is still the standard treatment for desmoid-type fibromatosis (DF). Recently, the Institut Gustave Roussy (IGR), Villejuif, France, reported a series of patients treated with a front-line conservative approach (no surgery and no radiotherapy). The disease remained stable in more than half of patients. This study was designed to evaluate this approach on the natural history of the disease in a larger series of patients. A total of 142 patients presenting to the IGR or Istituto Nazionale Tumori (INT), Milan, Italy, were initially treated using a front-line deliberately conservative policy. Their progression-free survival (PFS) was observed and a multivariate analysis was performed for major clinical variables. Seventy-four patients presented with primary tumor, 68 with recurrence. Eighty-three patients received a "wait & see" policy (W&S), whereas 59 were initially offered medical therapy (MT), mainly hormonal therapy and chemotherapy. A family history of sporadic colorectal cancer was present in 8% of patients. The 5-year PFS was 49.9% for the W&S group and 58.6% for the medically treated patients (P = 0.3196). Similar results emerged for primary and recurrent DF. Multivariate analysis identified no clinical variables as independent predictors of PFS. In the event of progression, all patients were subsequently managed safely. A conservative policy could be a safe approach to primary and recurrent DF, which could avoid unnecessary morbidity from surgery and/or radiation therapy. Half of patients had medium-term stable disease after W&S or MT. A multidisciplinary, stepwise approach should be prospectively tested in DF.

Shifting chronic disease management from hospitals to primary care in Estonian health system: analysis of national panel data

PubMed Central

Atun, Rifat; Gurol–Urganci, Ipek; Hone, Thomas; Pell, Lisa; Stokes, Jonathan; Habicht, Triin; Lukka, Kaija; Raaper, Elin; Habicht, Jarno

2016-01-01

Background Following independence from the Soviet Union in 1991, Estonia introduced a national insurance system, consolidated the number of health care providers, and introduced family medicine centred primary health care (PHC) to strengthen the health system. Methods Using routinely collected health billing records for 2005–2012, we examine health system utilisation for seven ambulatory care sensitive conditions (ACSCs) (asthma, chronic obstructive pulmonary disease [COPD], depression, Type 2 diabetes, heart failure, hypertension, and ischemic heart disease [IHD]), and by patient characteristics (gender, age, and number of co–morbidities). The data set contained 552 822 individuals. We use patient level data to test the significance of trends, and employ multivariate regression analysis to evaluate the probability of inpatient admission while controlling for patient characteristics, health system supply–side variables, and PHC use. Findings Over the study period, utilisation of PHC increased, whilst inpatient admissions fell. Service mix in PHC changed with increases in phone, email, nurse, and follow–up (vs initial) consultations. Healthcare utilisation for diabetes, depression, IHD and hypertension shifted to PHC, whilst for COPD, heart failure and asthma utilisation in outpatient and inpatient settings increased. Multivariate regression indicates higher probability of inpatient admission for males, older patient and especially those with multimorbidity, but protective effect for PHC, with significantly lower hospital admission for those utilising PHC services. Interpretation Our findings suggest health system reforms in Estonia have influenced the shift of ACSCs from secondary to primary care, with PHC having a protective effect in reducing hospital admissions. PMID:27648258

Risk of Falls in Parkinson's Disease: A Cross-Sectional Study of 160 Patients

PubMed Central

Contreras, Ana; Grandas, Francisco

2012-01-01

Falls are a major source of disability in Parkinson's disease. Risk factors for falling in Parkinson's disease remain unclear. To determine the relevant risk factors for falling in Parkinson's disease, we screened 160 consecutive patients with Parkinson's disease for falls and assessed 40 variables. A comparison between fallers and nonfallers was performed using statistical univariate analyses, followed by bivariate and multivariate logistic regression, receiver-operating characteristics analysis, and Kaplan-Meier curves. 38.8% of patients experienced falls since the onset of Parkinson's disease (recurrent in 67%). Tinetti Balance score and Hoehn and Yahr staging were the best independent variables associated with falls. The Tinetti Balance test predicted falls with 71% sensitivity and 79% specificity and Hoehn and Yahr staging with 77% sensitivity and 71% specificity. The risk of falls increased exponentially with age, especially from 70 years onward. Patients aged >70 years at the onset of Parkinson's disease experienced falls significantly earlier than younger patients. PMID:22292126

Cardiorespiratory Fitness is Associated with Reduced Risk of Respiratory Diseases in Middle-Aged Caucasian Men: A Long-Term Prospective Cohort Study.

PubMed

Kunutsor, Setor K; Laukkanen, Tanjaniina; Laukkanen, Jari A

2017-10-01

Cardiorespiratory fitness (CRF), an index of cardiac and respiratory functioning, is strongly associated with a reduced risk of adverse health outcomes. We aimed to assess the prospective association of CRF with the risk of respiratory diseases (defined as chronic obstructive pulmonary disease, pneumonia, or asthma). Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed in 1974 middle-aged men. During a median follow-up of 25.7 years, 382 hospital diagnosed respiratory diseases were recorded. Cardiorespiratory fitness was linearly associated with risk of respiratory diseases. In analysis adjusted for several established and potential risk factors, the hazard ratio (HR) (95% CI) for respiratory diseases was 0.63 (0.45-0.88), when comparing extreme quartiles of CRF levels. The corresponding multivariate adjusted HR (95% CI) for pneumonia was 0.67 (0.48-0.95). Our findings indicate a graded inverse and independent association between CRF and the future risk of respiratory diseases in a general male Caucasian population.

Determinants of Adiponectin Levels in Patients with Chronic Systolic Heart Failure

PubMed Central

Biolo, Andreia; Shibata, Rei; Ouchi, Noriyuki; Kihara, Shinji; Sonoda, Mina; Walsh, Kenneth; Sam, Flora

2010-01-01

Adiponectin, an adipocytokine, is secreted by adipocytes and mediates anti-hypertrophic and anti-inflammatory effects in the heart. Plasma concentrations of adiponectin are decreased in obesity, insulin resistance and obesity-associated conditions such as hypertension and coronary heart disease. However, a paradoxical increase in adiponectin levels is observed in human systolic heart failure (HF). We sought to investigate the determinants of adiponectin levels in patients with chronic systolic HF. Total adiponectin levels were measured in 99 patients with stable HF and left ventricular (LV) ejection fraction (EF) <40%. Determinants of adiponectin levels by univariate analysis were included in a multivariate linear regression model. At baseline patients were 62% black, 63% male, mean age of 60±13 years, LVEF of 21±9% and a body mass index (BMI) of 30.6±6.7kg/m2. Mean adiponectin levels were 15.8±15µg/ml. Beta-blocker use, BMI, and blood urea nitrogen (BUN) were significant determinants of adiponectin levels by multivariate analysis. LV mass, structure, and LVEF were not related to adiponectin levels by multivariate analysis. Interestingly, the effect of beta-blocker therapy was most marked in non-obese patients with BMI < 30kg/m2. In conclusion, in chronic systolic HF patients, beta-blocker therapy is correlated with lower adiponectin levels, especially in non-obese patients. This relation should be taken into account when studying the complex role of adiponectin in chronic systolic HF. PMID:20381668

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

PubMed

Hayes, Don; Kopp, Benjamin T; Tobias, Joseph D; Woodley, Frederick W; Mansour, Heidi M; Tumin, Dmitry; Kirkby, Stephen E

2015-12-01

Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

Increased risk for complications following removal of hardware in patients with liver disease, pilon or pelvic fractures: A regression analysis.

PubMed

Brown, Bryan D; Steinert, Justin N; Stelzer, John W; Yoon, Richard S; Langford, Joshua R; Koval, Kenneth J

2017-12-01

Indications for removing orthopedic hardware on an elective basis varies widely. Although viewed as a relatively benign procedure, there is a lack of data regarding overall complication rates after fracture fixation. The purpose of this study is to determine the overall short-term complication rate for elective removal of orthopedic hardware after fracture fixation and to identify associated risk factors. Adult patients indicated for elective hardware removal after fracture fixation between July 2012 and July 2016 were screened for inclusion. Inclusion criteria included patients with hardware related pain and/or impaired cosmesis with complete medical and radiographic records and at least 3-month follow-up. Exclusion criteria were those patients indicated for hardware removal for a diagnosis of malunion, non-union, and/or infection. Data collected included patient age, gender, anatomic location of hardware removed, body mass index, ASA score, and comorbidities. Overall complications, as well as complications requiring revision surgery were recorded. Statistical analysis was performed with SPSS 20.0, and included univariate and multivariate regression analysis. 391 patients (418 procedures) were included for analysis. Overall complication rates were 8.4%, with a 3.6% revision surgery rate. Univariate regression analysis revealed that patients who had liver disease were at significant risk for complication (p=0.001) and revision surgery (p=0.036). Multivariate regression analysis showed that: 1) patients who had liver disease were at significant risk of overall complication (p=0.001) and revision surgery (p=0.039); 2) Removal of hardware following fixation for a pilon had significantly increased risk for complication (p=0.012), but not revision surgery (p=0.43); and 3) Removal of hardware for pelvic fixation had a significantly increased risk for revision surgery (p=0.017). Removal of hardware following fracture fixation is not a risk-free procedure. Patients with liver disease are at increased risk for complications, including increased risk for needing revision surgery following hardware removal. Patients having hardware removed following fixation for pilon fractures also are at increased risk for complication, although they may not require a return trip to the operating room. Finally, removal of pelvic hardware is associated with a higher return to the operating room. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide.

PubMed

Fukumoto, Risa; Kawai, Makoto; Minai, Kosuke; Ogawa, Kazuo; Yoshida, Jun; Inoue, Yasunori; Morimoto, Satoshi; Tanaka, Toshikazu; Nagoshi, Tomohisa; Ogawa, Takayuki; Yoshimura, Michihiro

2017-01-01

It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development. The study population consisted of 3,457 patients consecutively admitted to our institution. The possible comorbid condition of VHD and CAD and the factors that influence the comorbidity were examined by covariance structure analysis and multivariate analysis. The distribution of the patients with VHD and those with CAD in the histograms showed that the incidence of VHD and the severity of CAD rose with seniority in appearance. The real statistical analysis was planned by covariance structure analysis. The current path model revealed that aging was associated with VHD and CAD severity (P < 0.001 for each); however, as a notable result, there was an inverse association regarding the comorbid condition between VHD and CAD (Correlation coefficient [β]: -0.121, P < 0.001). As the second objective, to clarify the factors leading to this inverse association, the contribution of conventional risk factors, such as age, gender, hypertension, smoking, diabetes, obesity and dyslipidemia, to VHD and CAD were examined by multivariate analysis. However, these factors did not exert an opposing effect on VHD and CAD, and the inverse association defied explanation. Since different pathological mechanisms may contribute to the formation of VHD and CAD, a differentially proposed path model using plasma BNP revealed that an increase in plasma BNP being drawn by VHD suppressed the progression of CAD (β: -0.465, P < 0.001). The incidence of VHD and CAD showed a significant conflicting relationship. This result supported the likely presence of unknown diverse mechanisms on top of the common cascade of atherosclerosis. Among them, the continuous elevation of plasma BNP due to VHD might be one of the explicable factors suppressing the progression of CAD.

PAI-1, CAIX and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

PubMed

Peterle, Gabriela Tonini; Maia, Lucas Lima; Trivilin, Leonardo Oliveira; de Oliveira, Mayara Mota; Dos Santos, Joaquim Gasparini; Mendes, Suzanny Oliveira; Stur, Elaine; Agostini, Lidiane Pignaton; Rocha, Lília Alves; Moysés, Raquel Ajub; Cury, Patrícia Maluf; Nunes, Fábio Daumas; Louro, Iúri Drumond; Dos Santos, Marcelo; da Silva, Adriana Madeira Álvares

2018-04-25

In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX) and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between proteins expressions and clinicopathological parameters and prognosis were analyzed. Positive PAI-1 membrane expression was significantly associated with local disease relapse (p=0.027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR=14.49; CI=1.40-150.01, p=0.025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (p=0.027). Strong CAIX membrane expression was significantly associated with local disease-free survival (p=0.038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (p=0.025) and with disease-specific survival (p=0.022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR=2.84; CI=1.02-7.87, p=0.045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (p=0.035). Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

PubMed Central

Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Thi Huong, Du Le; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

2014-01-01

Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate. PMID:25379192

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

PubMed

Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Le Thi Huong, Du; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

2014-01-01

Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

Predictors of associated autoimmune diseases (AAID) in families with type 1 diabetes (T1D). Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

PubMed Central

Wägner, Ana M; Santana, Ángelo; Hernández, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Didac

2011-01-01

Background Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAID) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAID in the Type 1 Diabetes Genetics Consortium (T1DGC) data set. Methods 3263 families with at least 2 siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD and anti-IA-2 were measured and HLA-genotyping was performed. Siblings with T1D with and without AAID were compared and a multivariate regression analysis was performed to find predictors of AAID. T1D-associated HLA haplotypes were defined as the 4 most susceptible and protective, respectively. Results AAID was present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, and there was a female predominance and more family history of AAID in the group with AAID, as well as more frequent anti-GAD and less frequent anti-IA2 positivity. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAID. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAID. Conclusions In patients with T1D, the presence of AAID is associated with female predominance, more frequent family history of AAID, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. PMID:21744463

Predictors of associated autoimmune diseases in families with type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium.

PubMed

Wägner, Ana M; Santana, Angelo; Herńndez, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Dídac

2011-07-01

Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAIDs) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAIDs in the Type 1 Diabetes Genetics Consortium data set. Three thousand two hundred and sixty-three families with at least two siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD (glutamic acid decarboxylase) and anti-protein tyrosine phosphatase (IA-2) were measured and human leukocyte antigen (HLA) genotyping was performed. Siblings with T1D with and without AAIDs were compared and a multivariate regression analysis was performed to find predictors of AAIDs. T1D-associated HLA haplotypes were defined as the four most susceptible and protective, respectively. One or more AAIDs were present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, there was a female predominance and more family history of AAIDs in the group with AAIDs, as well as more frequent anti-GAD and less frequent anti-IA-2 antibodies. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAIDs. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAIDs. In patients with T1D, the presence of AAIDs is associated with female predominance, more frequent family history of AAIDs, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. Copyright © 2011 John Wiley & Sons, Ltd.

Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

2018-06-05

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality. © RSNA, 2018 Online supplemental material is available for this article.

Multivariate Longitudinal Analysis with Bivariate Correlation Test

PubMed Central

Adjakossa, Eric Houngla; Sadissou, Ibrahim; Hounkonnou, Mahouton Norbert; Nuel, Gregory

2016-01-01

In the context of multivariate multilevel data analysis, this paper focuses on the multivariate linear mixed-effects model, including all the correlations between the random effects when the dimensional residual terms are assumed uncorrelated. Using the EM algorithm, we suggest more general expressions of the model’s parameters estimators. These estimators can be used in the framework of the multivariate longitudinal data analysis as well as in the more general context of the analysis of multivariate multilevel data. By using a likelihood ratio test, we test the significance of the correlations between the random effects of two dependent variables of the model, in order to investigate whether or not it is useful to model these dependent variables jointly. Simulation studies are done to assess both the parameter recovery performance of the EM estimators and the power of the test. Using two empirical data sets which are of longitudinal multivariate type and multivariate multilevel type, respectively, the usefulness of the test is illustrated. PMID:27537692

Multivariate Longitudinal Analysis with Bivariate Correlation Test.

PubMed

Adjakossa, Eric Houngla; Sadissou, Ibrahim; Hounkonnou, Mahouton Norbert; Nuel, Gregory

2016-01-01

In the context of multivariate multilevel data analysis, this paper focuses on the multivariate linear mixed-effects model, including all the correlations between the random effects when the dimensional residual terms are assumed uncorrelated. Using the EM algorithm, we suggest more general expressions of the model's parameters estimators. These estimators can be used in the framework of the multivariate longitudinal data analysis as well as in the more general context of the analysis of multivariate multilevel data. By using a likelihood ratio test, we test the significance of the correlations between the random effects of two dependent variables of the model, in order to investigate whether or not it is useful to model these dependent variables jointly. Simulation studies are done to assess both the parameter recovery performance of the EM estimators and the power of the test. Using two empirical data sets which are of longitudinal multivariate type and multivariate multilevel type, respectively, the usefulness of the test is illustrated.

Multiplex analysis of cytokines as biomarkers that differentiate benign and malignant thyroid diseases

PubMed Central

Linkov, Faina; Ferris, Robert L.; Yurkovetsky, Zoya; Marrangoni, Adele; Velikokhatnaya, Lyudmila; Gooding, William; Nolan, Brian; Winans, Matthew; Siegel, Eric R.; Lokshin, Anna; Stack, Brendan C.

2008-01-01

Thyroid cancer incidence is increasing, and its diagnosis can be challenging. Fine needle biopsy, the principal clinical tool to make a tissue diagnosis, leads to inconclusive diagnoses in up to 30% of the cases, leading to surgery. Advances in proteomics are improving abilities to diagnose malignant conditions using small samples of tissue or body fluids. We hypothesized that analysis of serum growth factors would uncover diagnostically informative differences between benign and malignant thyroid conditions. Using xMAP profiling, we evaluated concentrations of 19 cytokines, chemokines, and growth factors. We used sera from 23 patients with cancer (Malignant group), 24 patients with benign nodular thyroid disease (Benign group), and 23 healthy subjects (Normal group). In univariate analysis, five factors (epithelial growth factor, hepatocyte growth factor, Interleukins-5 and -8, and regulated upon activation, normally T-expressed and presumably secreted (RANTES) distinguished subjects with thyroid disease from the Normal group. In multivariate analysis, the set {Interleukin-8, hepatocyte growth factor, monocyte-induced γ interferon, interleukin-12 p40} achieved noteworthy discrimination between Benign and Malignant groups (area under the receiver operating characteristics curve was 0.81 (95% confidence interval: 0.65–0.90)). Multiplex panels of serum biomarkers may be promising tools to diagnose cancer in patients presenting with evidence of nodular thyroid disease. PMID:19234619

Patent ductus arteriosus and indomethacin treatment as independent risk factors for plus disease in retinopathy of prematurity.

PubMed

Tsui, Irena; Ebani, Edward; Rosenberg, Jamie B; Lin, Juan; Angert, Robert M; Mian, Umar

2013-01-01

To examine whether clinically significant patent ductus arteriosus (PDA) or indomethacin treatment are associated with plus disease or retinopathy of prematurity (ROP) requiring treatment. Retrospective, cross-sectional study. Charts were reviewed for gestational age, birth weight, birth head circumference, birth length, maternal characteristics, gender, bronchopulmonary dysplasia, neurologic comorbidities, PDA and its treatments, gastrointestinal comorbidities, blood transfusions, and sepsis. Main outcome measures were increased rates of plus disease or ROP requiring treatment. A total of 450 premature infants screened for ROP in a mid-sized, urban neonatal intensive care unit were included. On univariate analysis, gestational age, birth weight, birth head circumference, birth length, bronchopulmonary dysplasia, neurologic comorbidities, PDA and its treatments, gastrointestinal comorbidities, and sepsis were significantly correlated to plus disease and ROP requiring treatment. PDA was significantly associated with bronchopulmonary dysplasia, neurologic comorbidities, sepsis, and blood transfusions (P < .0001). With type 3 multivariate analysis, only gestational age and bronchopulmonary dysplasia were independent risk factors for ROP. PDA and indomethacin were associated with plus disease and ROP requiring treatment on univariate analysis but this was not significant after adjusting for other risk factors. PDA was also strongly related to bronchopulmonary dysplasia and blood transfusions, which may explain its effect on ROP. Copyright 2013, SLACK Incorporated.

Sociodemographic profile of children with Kawasaki disease in North India.

PubMed

Prakash, Jeya; Singh, Surjit; Gupta, Anju; Bharti, Bhavneet; Bhalla, A K

2016-03-01

Kawasaki disease (KD) is now the commonest cause of acquired heart disease in children in developed countries. KD occurs all over the world, including developing countries. The present study steps out to explore our hypothesis, driven by clinical observation over the last 18 years, whether children with KD in North India are of a higher socioeconomic status than children with other rheumatologic diseases. One hundred consecutive children with KD, registered in Pediatric Rheumatology Clinic before January 2011, were enrolled as cases. Children with other rheumatologic diseases were taken as controls. Assessment of socioeconomic status was done by administering the Aggarwal scale. Data were collected through interview. Statistical analysis was done using SPSS package version 16. On univariate analysis, male sex, higher educational status of parents, urban residence, immunization status being complete, and higher scores on Aggarwal scale were found to be significantly associated with KD. On multivariate analysis, only male sex and urban residence were found to be significantly associated with KD (p < 0.001). Families of children with KD tend to have a better sociodemographic profile when compared with other pediatric rheumatologic disorders in North India. These results, however, need to be replicated in a multicentric study for any firm conclusions to be drawn.

MAOA, MTHFR, and TNF-β genes polymorphisms and personality traits in the pathogenesis of migraine.

PubMed

Ishii, Masakazu; Shimizu, Shunichi; Sakairi, Yuki; Nagamine, Ayumu; Naito, Yuika; Hosaka, Yukiko; Naito, Yuko; Kurihara, Tatsuya; Onaya, Tomomi; Oyamada, Hideto; Imagawa, Atsuko; Shida, Kenji; Takahashi, Johji; Oguchi, Katsuji; Masuda, Yutaka; Hara, Hajime; Usami, Shino; Kiuchi, Yuji

2012-04-01

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.

Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, David H.A., E-mail: dhanguyen@yahoo.com; Departement de Radio-Oncologie, Hopital Maisonneuve-Rosemont, Montreal, Quebec; Truong, Pauline T.

2012-09-01

Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRTmore » consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease, clear margins, and distant disease limited to one subsite, bone-only involvement, or fewer than five metastatic lesions.« less

Metabolomic profiling of doxycycline treatment in chronic obstructive pulmonary disease.

PubMed

Singh, Brajesh; Jana, Saikat K; Ghosh, Nilanjana; Das, Soumen K; Joshi, Mamata; Bhattacharyya, Parthasarathi; Chaudhury, Koel

2017-01-05

Serum metabolic profiling can identify the metabolites responsible for discrimination between doxycycline treated and untreated chronic obstructive pulmonary disease (COPD) and explain the possible effect of doxycycline in improving the disease conditions. 1 H nuclear magnetic resonance (NMR)-based metabolomics was used to obtain serum metabolic profiles of 60 add-on doxycycline treated COPD patients and 40 patients receiving standard therapy. The acquired data were analyzed using multivariate principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). A clear metabolic differentiation was apparent between the pre and post doxycycline treated group. The distinguishing metabolites lactate and fatty acids were significantly down-regulated and formate, citrate, imidazole and l-arginine upregulated. Lactate and folate are further validated biochemically. Metabolic changes, such as decreased lactate level, inhibited arginase activity and lowered fatty acid level observed in COPD patients in response to add-on doxycycline treatment, reflect the anti-inflammatory action of the drug. Doxycycline as a possible therapeutic option for COPD seems promising. Copyright © 2016 Elsevier B.V. All rights reserved.

Outcome and prognostic factors in single brain metastases from small-cell lung cancer.

PubMed

Bernhardt, Denise; Adeberg, Sebastian; Bozorgmehr, Farastuk; Opfermann, Nils; Hörner-Rieber, Juliane; König, Laila; Kappes, Jutta; Thomas, Michael; Unterberg, Andreas; Herth, Felix; Heußel, Claus Peter; Warth, Arne; Debus, Jürgen; Steins, Martin; Rieken, Stefan

2018-02-01

Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.

Rapid discrimination of sea buckthorn berries from different H. rhamnoides subspecies by multi-step IR spectroscopy coupled with multivariate data analysis

NASA Astrophysics Data System (ADS)

Liu, Yue; Zhang, Ying; Zhang, Jing; Fan, Gang; Tu, Ya; Sun, Suqin; Shen, Xudong; Li, Qingzhu; Zhang, Yi

2018-03-01

As an important ethnic medicine, sea buckthorn was widely used to prevent and treat various diseases due to its nutritional and medicinal properties. According to the Chinese Pharmacopoeia, sea buckthorn was originated from H. rhamnoides, which includes five subspecies distributed in China. Confusion and misidentification usually occurred due to their similar morphology, especially in dried and powdered forms. Additionally, these five subspecies have vital differences in quality and physiological efficacy. This paper focused on the quick classification and identification method of sea buckthorn berry powders from five H. rhamnoides subspecies using multi-step IR spectroscopy coupled with multivariate data analysis. The holistic chemical compositions revealed by the FT-IR spectra demonstrated that flavonoids, fatty acids and sugars were the main chemical components. Further, the differences in FT-IR spectra regarding their peaks, positions and intensities were used to identify H. rhamnoides subspecies samples. The discrimination was achieved using principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). The results showed that the combination of multi-step IR spectroscopy and chemometric analysis offered a simple, fast and reliable method for the classification and identification of the sea buckthorn berry powders from different H. rhamnoides subspecies.

Apolipoprotein E4 serum concentration for increased sensitivity and specificity of diagnosis of drug treated Alzheimer's disease patients vs. drug treated parkinson's disease patients vs. age-matched normal controls.

PubMed

Goldknopf, Ira L; Park, Helen R; Sabbagh, Marwan

2012-12-01

Inasmuch as Alzheimer's disease (AD) is difficult to diagnose, patients with suspected dementias are often given FDA approved medications, including donepezil, rivastigmine, memantine HCl, or a combination, prior to diagnosis, and some respond with improved cognition. The present study demonstrates how concentrations of a select group of serum protein biomarkers can provide the basis for sensitive and specific differential diagnosis of AD in drug treated patients. Optimization is addressed by taking into account whether the patients and controls have or do not have increased risk of AD die to the presence or absence of Apolipoprotein E4. For differential diagnosis of AD, prospectively collected newly drawn blood serum samples were obtained from drug treated Alzheimer's disease and Parkinson's disease patients from a first (39 drug treated DTAD, and 31 age matched normal controls) and second medical center (56 drug treated DTPD, 47 age-matched normal controls). Analytically validated quantitative 2D gel electrophoresis (%CV ≤ 20%; LOD ≥ 0.5 ng/spot, 300 μg/ml of blood serum) was employed with patient and control sera for differential diagnosis of AD. Protein quantitation was subjected to statistical analysis by single variable Dot, Box and Whiskers and Receiver Operator Characteristics (ROC) plots for individual biomarker performance, and multivariate linear discriminant analysis for joint performance of groups of biomarkers. Protein spots were identified and characterized by LC MS/MS of in-gel trypsin digests, amino acid sequence spans of the identified peptides, and the protein spot molecular weights and isoelectric points. The single variable statistical profiles of 58 individual protein biomarker concentrations of the DTAD patient group differed from those of the normal and/or the disease control groups. Multivariate linear discriminant analysis of blood serum concentrations of the 58 proteins distinguished drug treated Alzheimer's disease (DTAD) patients from drug treated Parkinson's disease (DTPD) patients and age matched normal controls (collectively not-DTAD, DTAD Sensitivity 87.2%, Not-DTAD Specificity 87.2). Moreover, when the patients and controls were stratified into carriers or non-carriers of Alzheimer's high risk Apolipoprotein E 4 allele and/or the Apolipoprotein E4 protein, the DTAD, DTPD and control Apo E4 (+) profiles were more divergent from one another than the corresponding Apo E4 (-) profiles. Multivariate stepwise linear discriminant analysis selected 17 of the 58 biomarkers as optimal and complimentary for distinguishing Apo E4 (+) DTAD patients from Apo E4 (+) DTPD and Apo E4 (+) controls (collectively Apo E4 (+) not-DTAD, DTAD Sensitivity 100%, not-DTAD Specificity 100%) and 22 of the 58 biomarkers for distinguishing Apo E4 (-) DTAD patients from Apo E4 (-) DTPD and Apo E4 (-) controls (collectively Apo E4 (-) not-DTAD, DTAD Sensitivity 94.4%, not- DTAD Specificity 94.4%). Only 6 of the selected proteins were common to both the Apo E4 (+) and the Apo E4 (-) discriminant functions. Recombining of the results of Apo E4 (+) and Apo E4 (-) discriminations provided overall sensitivity for total DTAD of 97.4% and specificity for total not-DTAD of 95.7%. These results can form the basis of a blood test for differential diagnosis of Alzheimer's disease patients already under treatment (DTAD) by anti dementia drugs, including donepezil, rivastigmine, memantine HCl, or a combination thereof. Also, the profile differences and the rise in specificity and sensitivity obtained by handling the Apo E4 (+) and Apo E4 (-) groups separately supports the concept that they are different patient and control populations in terms of the "normal" physiology, the pathophysiology of disease, and the response to drug treatment. Taking that into account enables increased sensitivity and specificity of differential diagnosis of Alzheimer's disease.

High uptake of hepatitis C virus treatment in HIV/hepatitis C virus co-infected patients attending an integrated HIV/hepatitis C virus clinic.

PubMed

Kieran, J; Dillon, A; Farrell, G; Jackson, A; Norris, S; Mulcahy, F; Bergin, C

2011-10-01

Hepatitis C virus (HCV) is a major cause of liver disease in HIV-infected patients. The HCV treatment outcomes and barriers to HCV referral were examined in a centre with a HIV/HCV co-infection clinic. Patients who were antibody positive for both HIV and HCV between 1987 and January 2009 were identified. A retrospective chart review was undertaken. Multivariate analysis was performed to assess predictors of HCV clinic referral. Data were collected on 386 HIV/HCV patients; 202/386 had been referred to the co-infection clinic and 107/202 had HCV treatment. In addition, 29/202 were undergoing pretreatment work-up. Overall sustained virologic response (SVR) was 44%; SVR was equivalent in those who acquired HIV/HCV infection from intravenous drug use (IDU) and others. On multivariate analysis, patients who missed appointments, were younger, with active IDU and advanced HIV and who were not offered HCV treatment were less likely to be referred to the clinic. Patients attending the clinic were more likely to have been screened for hepatocellular carcinoma than those attending the general HIV service. Two-thirds of patients referred to the clinic had engaged with the HCV treatment programme. Dedicated co-infection clinics lower the threshold for treatment and improve management of liver disease in co-infected patients.

Development of upper tract stones in patients with congenital neurogenic bladder.

PubMed

Stephany, Heidi A; Clayton, Douglass B; Tanaka, Stacy T; Thomas, John C; Pope, John C; Brock, John W; Adams, Mark C

2014-02-01

Patients with neurogenic bladder are at increased risk of developing upper tract stones. We hypothesized that patients with lower urinary tract stone disease are at greater risk of developing upper tract stones. We performed a 10-year retrospective case-control study of patients with neurogenic bladder to determine the association between bladder and upper tract stones. Independent risk factors for upper tract stones were assessed. Cases and controls were matched 1:1. Univariable analysis was performed by Fisher's exact test and the Mann-Whitney U test. Multivariable logistic regression was performed. 52 cases and controls were identified. Cases were significantly more likely to be non-ambulatory, have bowel-urinary tract interposition, thoracic level dysraphism, and history of bladder stones. On multivariable analysis, independent predictors of stone formation were male sex (OR 2.82; p = 0.02), dysraphism involving the thoracic spine (OR 3.37; p = 0.014) bowel-urinary tract interposition (OR 2.611; p = 0.038), and a history of bladder stones (OR 3.57; p = 0.015). Patients with neurogenic bladder are at increased risk for upper tract stones. The presence of bladder stones may herald the development of upper tract stones. The predictors of stone disease identified should guide prospective studies to better understand the natural history of upper tract stone development in this population. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

[Impact of heat waves on non-accidental deaths in Jinan, China].

PubMed

Zhang, J; Liu, S Q; Zhou, L; Gong, S P; Liu, Y L; Zhang, Y; Zhang, J

2016-02-20

To assess the impact of heat waves on non-accidental deaths, and to investigate the influencing factors for deaths caused by heat waves in Jinan, China. Daily death data and meteorological data for summer days with or without heat waves in Jinan from 2012 to 2014 were collected, and a cross-over analysis was conducted to evaluate the influence of heat waves on non-accidental deaths and deaths caused by other reasons. The univariate and multivariate logistic regression models were used to investigate the influencing factors for deaths caused by heat waves. The risks of non-accidental deaths and deaths caused by circulation system diseases during the days with heat waves were 1.82 times(95% CI: 1.47~2.36) and 1.53 times(95% CI: 1.14~2.07) those during the days without heat waves. The multivariate logistic regression analysis showed that old age(≥75 years)(OR=1.184, 95% CI: 1.068~1.313), low educational level(OR=1.187, 95% CI: 1.064~1.324), and deaths outside hospital(OR=1.105, 95% CI: 1.009~1.210) were associated with the high risk of deaths during the days with heat waves. Heat waves significantly increase the risk of non-accidental deaths and deaths caused by circulation system diseases in Jinan, and the deaths during the days with heat waves are related to age, educational level, and place of death.

CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers

PubMed Central

Vedeld, Hege Marie; Merok, Marianne; Jeanmougin, Marine; Danielsen, Stine A.; Honne, Hilde; Presthus, Gro Kummeneje; Svindland, Aud; Sjo, Ole H.; Hektoen, Merete; Eknæs, Mette; Nesbakken, Arild; Lothe, Ragnhild A.

2017-01-01

The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5‐markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni‐ and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (<60, 60‐74, ≥75 years). Patients with CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31‐2.63] and 1.89 [1.34‐2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P < 0.001), and MSS BRAF mutated tumors (P < 0.001), a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis (P < 0.01). Consistent results were found for all three age groups. To conclude, CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors. PMID:28542846

Novel, Objective, Multivariate Biomarkers Composed of Plasma Amino Acid Profiles for the Diagnosis and Assessment of Inflammatory Bowel Disease

PubMed Central

Hisamatsu, Tadakazu; Okamoto, Susumu; Hashimoto, Masaki; Muramatsu, Takahiko; Andou, Ayatoshi; Uo, Michihide; Kitazume, Mina T.; Matsuoka, Katsuyoshi; Yajima, Tomoharu; Inoue, Nagamu; Kanai, Takanori; Ogata, Haruhiko; Iwao, Yasushi; Yamakado, Minoru; Sakai, Ryosei; Ono, Nobukazu; Ando, Toshihiko; Suzuki, Manabu; Hibi, Toshifumi

2012-01-01

Background Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). Methodology and Principal Findings We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898–0.983) and 0.894 (95%CI: 0.853–0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853–0.935) and 0.849 (95%CI: 0.770–0.928), and correlated with clinical disease activity indexes for CD (rs = 0.592, 95%CI: 0.385–0.742, p<0.001) or UC (rs = 0.598, 95%CI: 0.452–0.713, p<0.001), respectively. Conclusions and Significance In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease. PMID:22303484

Multivariate Regression Analysis and Slaughter Livestock,

DTIC Science & Technology

AGRICULTURE, *ECONOMICS), (*MEAT, PRODUCTION), MULTIVARIATE ANALYSIS, REGRESSION ANALYSIS , ANIMALS, WEIGHT, COSTS, PREDICTIONS, STABILITY, MATHEMATICAL MODELS, STORAGE, BEEF, PORK, FOOD, STATISTICAL DATA, ACCURACY

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events

PubMed Central

Hoefer, Imo E.; Eijkemans, Marinus J. C.; Asselbergs, Folkert W.; Anderson, Todd J.; Britton, Annie R.; Dekker, Jacqueline M.; Engström, Gunnar; Evans, Greg W.; de Graaf, Jacqueline; Grobbee, Diederick E.; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; de Kleijn, Dominique P. V.; Lonn, Eva M.; Lorenz, Matthias W.; Mathiesen, Ellisiv B.; Nijpels, Giel; Okazaki, Shuhei; O’Leary, Daniel H.; Pasterkamp, Gerard; Peters, Sanne A. E.; Polak, Joseph F.; Price, Jacqueline F.; Robertson, Christine; Rembold, Christopher M.; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T.; Sitzer, Matthias; Stehouwer, Coen D. A.; Bots, Michiel L.; den Ruijter, Hester M.

2015-01-01

Background Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. Methods We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Results Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. Conclusion The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention. PMID:26134404

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

PubMed

Gijsberts, Crystel M; Groenewegen, Karlijn A; Hoefer, Imo E; Eijkemans, Marinus J C; Asselbergs, Folkert W; Anderson, Todd J; Britton, Annie R; Dekker, Jacqueline M; Engström, Gunnar; Evans, Greg W; de Graaf, Jacqueline; Grobbee, Diederick E; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; de Kleijn, Dominique P V; Lonn, Eva M; Lorenz, Matthias W; Mathiesen, Ellisiv B; Nijpels, Giel; Okazaki, Shuhei; O'Leary, Daniel H; Pasterkamp, Gerard; Peters, Sanne A E; Polak, Joseph F; Price, Jacqueline F; Robertson, Christine; Rembold, Christopher M; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T; Sitzer, Matthias; Stehouwer, Coen D A; Bots, Michiel L; den Ruijter, Hester M

2015-01-01

Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

T-pattern analysis for the study of temporal structure of animal and human behavior: a comprehensive review.

PubMed

Casarrubea, M; Jonsson, G K; Faulisi, F; Sorbera, F; Di Giovanni, G; Benigno, A; Crescimanno, G; Magnusson, M S

2015-01-15

A basic tenet in the realm of modern behavioral sciences is that behavior consists of patterns in time. For this reason, investigations of behavior deal with sequences that are not easily perceivable by the unaided observer. This problem calls for improved means of detection, data handling and analysis. This review focuses on the analysis of the temporal structure of behavior carried out by means of a multivariate approach known as T-pattern analysis. Using this technique, recurring sequences of behavioral events, usually hard to detect, can be unveiled and carefully described. T-pattern analysis has been successfully applied in the study of various aspects of human or animal behavior such as behavioral modifications in neuro-psychiatric diseases, route-tracing stereotypy in mice, interaction between human subjects and animal or artificial agents, hormonal-behavioral interactions, patterns of behavior associated with emesis and, in our laboratories, exploration and anxiety-related behaviors in rodents. After describing the theory and concepts of T-pattern analysis, this review will focus on the application of the analysis to the study of the temporal characteristics of behavior in different species from rodents to human beings. This work could represent a useful background for researchers who intend to employ such a refined multivariate approach to the study of behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

Can multivariate models based on MOAKS predict OA knee pain? Data from the Osteoarthritis Initiative

NASA Astrophysics Data System (ADS)

Luna-Gómez, Carlos D.; Zanella-Calzada, Laura A.; Galván-Tejada, Jorge I.; Galván-Tejada, Carlos E.; Celaya-Padilla, José M.

2017-03-01

Osteoarthritis is the most common rheumatic disease in the world. Knee pain is the most disabling symptom in the disease, the prediction of pain is one of the targets in preventive medicine, this can be applied to new therapies or treatments. Using the magnetic resonance imaging and the grading scales, a multivariate model based on genetic algorithms is presented. Using a predictive model can be useful to associate minor structure changes in the joint with the future knee pain. Results suggest that multivariate models can be predictive with future knee chronic pain. All models; T0, T1 and T2, were statistically significant, all p values were < 0.05 and all AUC > 0.60.

[Health status of immigrants arrived to Italian coast].

PubMed

Firenze, Alberto; Restivo, Vincenzo; Bonanno, Valentina; Aleo, Nicola; Pace, Stella; Marsala, Maria Grazia Laura; Palermo, Mario

2014-01-01

To analyze the factors involved in access to Emergency Department (ED) of undocumented immigrants in Lampedusa according to the country of origin. This is a retrospective observational study, carried out on newly arrived undocumented immigrants transferred to ED. Data were collected from medical records of Lampedusa ED between January 2012 and May 2013 on 326 undocumented immigrants. The outcomes evaluated are demographics characteristics and health condition of undocumented immigrants. In multivariate analysis associated factors to ED visits are: other pathologies rather than traumatic diseases (OR 0.22; p <0.001), younger age (OR 0.9; p <0.001) and female sex (OR 12.49; p=0.017) for Somalis; gastroenterological diseases (OR 2.55; p=0.026) and older age (OR 1.6; p=0.004) for Eritrean; neurological disease (OR 5.33; p=0.048) and male sex (OR 5.45; p=0.032) for Tunisian. This analysis shows that undocumented immigrants cannot be considered as a single population, because they generate a diversified set of pathological conditions.

Prevalence of spondyloarthritis symptom in inflammatory bowel disease patients: A questionnaire survey.

PubMed

Kamo, Kenta; Shuto, Toshihide; Haraguchi, Akihisa

2015-05-01

We clarified the prevalence of spondyloarthritis (SpA) symptom in inflammatory bowel disease (IBD). We performed the questionnaire survey of SpA symptom in IBD patients on their office visit. One hundred and thirty seven patients were evaluated. The SpA features group included 46 (33.6%) patients (32 Men). Among them there were 22 Crohn's disease (CD) patients and 24 ulcerative colitis (UC) patients. The patients had a mean age of 48.3 years with a mean disease duration of 12.3 years. Non-SpA group (66.4%) included 91 patients (49 Men). Among them there were 27 CD patients and 64 UC patients. The patients had a mean age of 43.3 years with a mean disease duration of 9.2 years. In univariate analysis, the SpA group (33.6%) had longer disease duration than non-SpA group (p < 0.05). However, age at onset and sex were not significantly different among the groups. Multivariate analysis showed that disease duration was independently associated with SpA symptom (OR, 1.05; 95% CI, 1-1.09; p = 0.036). The prevalence of SpA symptom was relatively higher than what we had expected. Physicians should consider SpA when they observe IBD patients with arthralgia, and refer them to an appropriate department if needed.

Coronary risk factors of angiographically assessed patients from Syria.

PubMed

al-Kateb, H; Zarzzour, W; Shameah, M; Juoma, M

1998-02-01

Predictors of coronary artery disease in an Arab population had not been defined well. We studied 192 male patients with suspected coronary artery disease, who underwent catheterization. We defined definite coronary artery disease as > 50% stenosis in any of three vessels. The effects of age, obesity, smoking, hypertension, diabetes, and lipid fractions were assessed by means of univariate and multivariate regression analysis. Coronary artery disease was present in 153 men (80%) and absent from 39 men. Patients without coronary artery disease were slightly younger, thinner, smoked less, and had lower cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels than did those who had coronary artery disease. By stepwise regression analysis, the best discriminators were body mass index (P = 0.0004), age (P = 0.0005), smoking (P = 0.014) and the apolipoprotein B:A-I ratio (P = 0.041). The strongest Pearson correlation coefficients for coronary artery disease were the ratio of total: high-density lipoprotein cholesterol levels (r = 0.26), the apolipoprotein B:A-I ratio (r = 0.26), and age (r = 0.25), all P < 0.0005. In this angiographically evaluated Syrian population, previously recognized, well-known risk factors appeared. Obesity, smoking, hypertension, diabetes, and elevated lipid levels are all amenable to correction. Syria should adopt the same secondary prevention strategies as those currently being practiced by non-Arab countries.

Urine Metabolomics Analysis for Biomarker Discovery and Detection of Jaundice Syndrome in Patients With Liver Disease*

PubMed Central

Wang, Xijun; Zhang, Aihua; Han, Ying; Wang, Ping; Sun, Hui; Song, Gaochen; Dong, Tianwei; Yuan, Ye; Yuan, Xiaoxia; Zhang, Miao; Xie, Ning; Zhang, He; Dong, Hui; Dong, Wei

2012-01-01

Metabolomics is a powerful new technology that allows for the assessment of global metabolic profiles in easily accessible biofluids and biomarker discovery in order to distinguish between diseased and nondiseased status information. Deciphering the molecular networks that distinguish diseases may lead to the identification of critical biomarkers for disease aggressiveness. However, current diagnostic methods cannot predict typical Jaundice syndrome (JS) in patients with liver disease and little is known about the global metabolomic alterations that characterize JS progression. Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication, and therapy. Therefore, the aim of this study is to find the potential biomarkers from JS disease by using a nontarget metabolomics method, and test their usefulness in human JS diagnosis. Multivariate data analysis methods were utilized to identify the potential biomarkers. Interestingly, 44 marker metabolites contributing to the complete separation of JS from matched healthy controls were identified. Metabolic pathways (Impact-value≥0.10) including alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies were found to be disturbed in JS patients. This study demonstrates the possibilities of metabolomics as a diagnostic tool in diseases and provides new insight into pathophysiologic mechanisms. PMID:22505723

Periodontal disease severity is associated with micronutrient intake.

PubMed

Luo, P-P; Xu, H-S; Chen, Y-W; Wu, S-P

2018-03-06

This study aimed to examine if specific micronutrients were associated with periodontal disease using data from the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Participants who were aged 30 years or more and received complete periodontal examinations were included. Regression analyses were performed to determine associations of variables of interest with periodontal disease. Data of 6415 NHANES participants were included in the analysis. Multivariable analysis revealed that less intake of vitamin A (adjusted odds ratio (aOR) = 1.784), vitamin B1 (aOR = 1.334), vitamin C (aOR = 1.401), vitamin E (aOR = 1.576), iron (aOR = 1.234), folate (aOR = 1.254) and phosphorus (aOR = 1.280) was associated with increased severity of periodontal disease. Compared with the highest level of vitamin D intake, the second highest level of vitamin D intake was associated with lower severity of periodontal disease (aOR = 0.727). Insufficient intake of vitamin A, B1, C and E, iron, folate and phosphorus was significantly associated with severity of periodontal disease. Results of the present study suggest that the above micronutrients may be increased in the diet or taken as dietary supplements in order to reduce severity of periodontal disease. © 2018 Australian Dental Association.

Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease.

PubMed

Martinez-Aguilar, Esther; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, Sebastián; Rodríguez, Jose A; Fernández-Alonso, Leopoldo; Páramo, Jose A; Roncal, Carmen

2017-11-01

The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with higher risk of cardiovascular (CV) complications and death in different atherosclerotic diseases, recent epidemiologic studies have challenged its prognostic utility. The aim of this study was to test the predictive value of HDL-C as a risk factor for ischemic events or death in symptomatic PAD patients. Clinical and demographic parameters of 254 symptomatic PAD patients were recorded. Amputation, ischemic coronary disease, cerebrovascular disease, and all-cause mortality were recorded during a mean follow-up of 2.7 years. Multivariate analyses showed that disease severity (critical limb ischemia) was significantly reduced in patients with normal HDL-C levels compared with the group with low HDL-C levels (multivariate analysis odds ratio, 0.09; 95% confidence interval [CI], 0.03-0.24). A decreased risk for mortality (hazard ratio, 0.46; 95% CI, 0.21-0.99) and major adverse CV events (hazard ratio, 0.38; 95% CI, 0.16-0.86) was also found in patients with normal vs reduced levels of HDL-C in both Cox proportional hazards models and Kaplan-Meier estimates, after adjustment for confounding factors. Reduced HDL-C levels were significantly associated with higher risk for development of CV complications as well as with mortality in PAD patients. These findings highlight the usefulness of this simple test for early identification of PAD patients at high risk for development of major CV events. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Factors associated with generic health-related quality of life in adult asthma patients in Germany: Cross-sectional study.

PubMed

Böhmer, Merle M; Brandl, Magdalena; Brandstetter, Susanne; Finger, Tamara; Fischer, Wiebke; Pfeifer, Michael; Apfelbacher, Christian

2017-04-01

Given a 9% lifetime prevalence of asthma in Germany and the impairment of health-related quality of life (HRQOL) that goes along with it, it is important to understand parameters affecting HRQOL in asthma patients. Objective of this study was therefore to determine factors associated with generic HRQOL in asthma patients. Data for cross-sectional analyses were obtained from the baseline of an ongoing cohort study. physician-diagnosed asthma; age ≥18 years; disease duration ≥3 months; no acute psychiatric/neurological disease; sufficient knowledge of German. HRQOL was assessed by the Short Form 12 Health Survey Questionnaire (SF-12), which comprises a physical (PCS-12) and a mental component (MCS-12). Information on a broad range of parameters potentially influencing HRQOL was collected by examining the patients' medical records and via a self-administered questionnaire. Those parameters were of socio-demographic, disease-specific, treatment-related or psychosocial nature. We conducted multivariable linear regression analyses to assess determinants of HRQOL. In total, 196 asthma patients participated in the study (mean age: 48 years (range: 18-90); 60.2% females). In multivariable analysis, PCS-12 was negatively associated with older age, being female, insufficient disease control, higher number of medications in tablet form and reporting symptoms of depression. MCS-12 was negatively associated with being female, living alone, insufficient disease control, and reporting symptoms of anxiety or depression. Focusing on disease control and screening for depression and anxiety may be promising approaches to improve HRQOL in adult asthma patients. If a patient shows alarming symptoms of anxiety and/or depression, the patient should then be referred for psychiatric treatment.

Female, Black, and Unmarried Patients Are More Likely to Present With Metastatic Bladder Urothelial Carcinoma.

PubMed

Klaassen, Zachary; DiBianco, John M; Jen, Rita P; Evans, Austin J; Reinstatler, Lael; Terris, Martha K; Madi, Rabii

2016-10-01

Although there are well-established risk factors for the diagnosis of bladder cancer, there is no consensus regarding risk factors for presentation of advanced or metastatic disease at diagnosis. The objective of this study was to identify the demographic and clinical factors associated with metastasis at diagnosis in patients with bladder urothelial carcinoma. Patients diagnosed with bladder urothelial carcinoma from 2004 to 2010 were identified in the Surveillance, Epidemiology, and End Results (SEER) database (n = 108,417). The primary outcome was metastatic disease at the time of diagnosis. Demographic and socioeconomic variables were analyzed, and multivariable logistic regression models were performed to generate odds ratios (OR) for factors associated with metastasis at diagnosis. Of patients with bladder cancer, 3018 (2.8%) had metastasis at diagnosis and 105,399 (97.2%) had nonmetastatic disease. Patients with metastatic disease at diagnosis were more frequently female (29.6% vs. 23.6%, P < .001), black (9.4% vs. 5.0%, P < .001), and unmarried (44.1% vs. 32.5%, P < .001) compared to patients with nonmetastatic disease. On multivariable analysis, the following characteristics were confirmed to be independently associated with metastatic disease at diagnosis: female gender (vs. male, OR 1.21), black race (vs. white, OR 1.71), unmarried (vs. married, OR 1.46), unemployed (OR 1.02), and foreign-born status (OR 1.01). Female gender, black race, unmarried, unemployed, and foreign-born status are independently associated with metastasis at diagnosis for bladder urothelial carcinoma. All clinicians should be aware of these potential health care disparities in order to involve social services and other support mechanisms in efforts to improve early care. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinically Non-Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation: Natural History and Outcomes after Surgical Resection with Curative Intent

PubMed Central

Merrill, Megan M.; Wood, Christopher G.; Tannir, Nizar M.; Slack, Rebecca S.; Babaian, Kara N.; Jonasch, Eric; Pagliaro, Lance C.; Compton, Zachary; Tamboli, Pheroze; Sircar, Kanishka; Pisters, Louis L.; Matin, Surena F.; Karam, Jose A.

2015-01-01

Purpose Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. While existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate post-nephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. Patients and Methods An IRB-approved review from 1986–2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. Results OS for the entire cohort (N=77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who were NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and RFS. Limitations include the retrospective nature of this study and relatively small sample size. Conclusions Long-term survival for patients with sRCC, even in clinically localized disease is poor. Aggressive surveillance of those who are NED following nephrectomy is essential and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted. PMID:25700975

Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors.

PubMed

Mariabeatrice, Principi; Andrea, Iannone; Giuseppe, Losurdo; Michela, Mangia; Endrit, Shahini; Francesca, Albano; Rizzi, Salvatore Fabio; La Fortezza, Rosa Federica; Rosa, Lovero; Antonella, Contaldo; Michele, Barone; Gioacchino, Leandro; Enzo, Ierardi; Alfredo, Di Leo

2018-04-23

Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma

PubMed Central

Palmieri, Giuseppe; Satriano, Sabrina MR; Budroni, Mario; Cossu, Antonio; Tanda, Francesco; Canzanella, Sergio; Caracò, Corrado; Simeone, Ester; Daponte, Antonio; Mozzillo, Nicola; Comella, Giuseppe; Castello, Giuseppe; Ascierto, Paolo A

2006-01-01

Background Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusion Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease. PMID:17107608

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma.

PubMed

Palmieri, Giuseppe; Satriano, Sabrina M R; Budroni, Mario; Cossu, Antonio; Tanda, Francesco; Canzanella, Sergio; Caracò, Corrado; Simeone, Ester; Daponte, Antonio; Mozzillo, Nicola; Comella, Giuseppe; Castello, Giuseppe; Ascierto, Paolo A

2006-11-15

Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (> or =2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.

Loss to follow-up in tuberculosis treatment and its relationship with patients' knowledge of the disease and other associated factors.

PubMed

Belchior, Aylana De S; Mainbourg, Evelyne Marie T; Ferreira-Gonçalves, Maria J

2016-01-01

To identify factors associated with loss to follow-up in Tuberculosis (TB) treatment, including patients' level of knowledge regarding treatment of this disease. 42 loss to follow-up cases and 84 control cases that were finishing the sixth month of their first treatment for tuberculosis were selected for this study. Primary data were gathered through interviews, while secondary data were obtained from the notification form of the disease, between December 2011 and April 2012. Factors associated with loss to follow-up were analyzed by means of a conditional logistic regression multivariate model for matched case-control groups. No significant differences were observed between loss to follow-up cases and controls regarding socioeconomic factors, lifestyle, clinical condition, treatment-related behaviors and the access of patients to sources of information on TB. In the regression multivariate analysis, significant associations with retreatment after loss to follow-up that were detected include: scarce knowledge on tuberculosis, lack of adherence to consultation during the current treatment, noncompliance with follow-up consultation deadline, smoking and HIV negative. When compared to controls, cases undergoing TB retreatment after loss to follow-up have less knowledge on the disease, which is a sign for the professionals responsible for health education of the need to invest more time and efforts in activities that help the patient understand the disease and its treatment, as well as to have higher levels of adherence. In addition, noncompliance with the follow-up consultation deadline, failure to attend consultations during the current treatment and smoking are also factors that may be influenced by poor knowledge on the disease, which leads to the treatment loss to follow-up.

Variation in Care of Inflammatory Bowel Diseases Patients in Crohn's and Colitis Foundation of America Partners: Role of Gastroenterologist Practice Setting in Disease Outcomes and Quality Process Measures.

PubMed

Weaver, Kimberly N; Kappelman, Michael D; Sandler, Robert S; Martin, Christopher F; Chen, Wenli; Anton, Kristen; Long, Millie D

2016-11-01

As variation in care has previously been linked to quality, we aimed to describe variations in inflammatory bowel diseases care by gastroenterology (GI) practice setting. We performed a cross-sectional study within the Crohn's and Colitis Foundation of America Partners and used bivariate analyses to compare patient characteristics by GI practice setting (GI-academic [GIA], GI-private, or GI-other). Regression models were used to describe the effects of provider type on steroid use, disease activity, and the quality of life. The study included 12,083 patients with inflammatory bowel diseases (7576 with Crohn's disease [CD] and 4507 with ulcerative colitis [UC]). Nearly 95% reported visiting a GI provider annually. Also, CD patients seen by GIA were younger, better educated, used less 5-aminosalicylate agents, and had higher biologic and immunomodulator use (P < 0.001 for all). On multivariate analysis of CD patients, GIA used less steroids when compared with GI-private (odds ratio, 0.84; 95% confidence interval, 0.67-1.06) or GI-other (odds ratio, 0.66; 95% confidence interval, 0.49-0.89). GIA patients were more likely to be in remission, have flu vaccine, and have better quality of life. UC patients seen by GIA were younger, had more hospitalizations, and previous surgery (P < 0.001 for all). No differences existed for steroid use, remission, flu vaccine, or quality of life for UC care on bivariate or multivariate analyses. Significant variations in care patterns and quality measures exist for CD across GI provider types, without similar variation in UC care. Interventions to reduce variations in care could improve the quality of care in CD.

Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: an analysis of Medicare claims data.

PubMed

Singh, Jasvinder A; Cleveland, John D

2017-10-01

To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly. In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models. There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol <200, 200-299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses <200, 200-299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings. Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.

PubMed

Bertoli, A M; Vilá, L M; Reveille, J D; Alarcón, G S

2008-04-01

To determine the features associated with acute onset systemic lupus erythaematosus (SLE). A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus

PubMed Central

Bertoli, A M; Vilá, L M; Reveille, J D; Alarcón, G S

2009-01-01

Objective To determine the features associated with acute onset systemic lupus erythaematosus (SLE). Methods A total of 631 SLE patients from LUMINA (for “lupus in minority populations: nature vs nurture”), a multiethnic (Hispanics, African–Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of ≥4 American College of Rheumatology (ACR) criteria for the classification of SLE in ≤4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortally, autoantibodies. HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (χ2 and Student t test) and multivariable (stepwise logistic regression) analyses. Results A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076–3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005–1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956–0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827–0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249–0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142–0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Conclusions Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE. PMID:17720721

Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

PubMed Central

Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

2016-01-01

Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

NT-proBNP Predicts All-Cause Mortality in a Population of Insurance Applicants, Follow-up Analysis and Further Observations.

PubMed

Fulks, Michael; Kaufman, Valerie; Clark, Michael; Stout, Robert L

2017-01-01

- Further refine the independent value of NT-proBNP, accounting for the impact of other test results, in predicting all-cause mortality for individual life insurance applicants with and without heart disease. - Using the Social Security Death Master File and multivariate analysis, relative mortality was determined for 245,322 life insurance applicants ages 50 to 89 tested for NT-proBNP (almost all based on age and policy amount) along with other laboratory tests and measurement of blood pressure and BMI. - NT-proBNP values ≤75 pg/mL included the majority of applicants denying heart disease and had the lowest risk, while values >500 pg/mL for females and >300 pg/mL for males had very high relative risk. Those admitting to heart disease had a higher mortality risk for each band of NT-proBNP relative to those denying heart disease but had a similar and equally predictive risk curve. - NT-proBNP is a strong independent predictor of all-cause mortality in the absence or presence of known heart disease but the range of values associated with increased risk varies by sex.

Emotion Risk-Factor in Patients with Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study).

PubMed

Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghei, Abbas

2015-05-17

Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) Was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases.

Multivariate calibration in Laser-Induced Breakdown Spectroscopy quantitative analysis: The dangers of a 'black box' approach and how to avoid them

NASA Astrophysics Data System (ADS)

Safi, A.; Campanella, B.; Grifoni, E.; Legnaioli, S.; Lorenzetti, G.; Pagnotta, S.; Poggialini, F.; Ripoll-Seguer, L.; Hidalgo, M.; Palleschi, V.

2018-06-01

The introduction of multivariate calibration curve approach in Laser-Induced Breakdown Spectroscopy (LIBS) quantitative analysis has led to a general improvement of the LIBS analytical performances, since a multivariate approach allows to exploit the redundancy of elemental information that are typically present in a LIBS spectrum. Software packages implementing multivariate methods are available in the most diffused commercial and open source analytical programs; in most of the cases, the multivariate algorithms are robust against noise and operate in unsupervised mode. The reverse of the coin of the availability and ease of use of such packages is the (perceived) difficulty in assessing the reliability of the results obtained which often leads to the consideration of the multivariate algorithms as 'black boxes' whose inner mechanism is supposed to remain hidden to the user. In this paper, we will discuss the dangers of a 'black box' approach in LIBS multivariate analysis, and will discuss how to overcome them using the chemical-physical knowledge that is at the base of any LIBS quantitative analysis.

Linear regression analysis and its application to multivariate chromatographic calibration for the quantitative analysis of two-component mixtures.

PubMed

Dinç, Erdal; Ozdemir, Abdil

2005-01-01

Multivariate chromatographic calibration technique was developed for the quantitative analysis of binary mixtures enalapril maleate (EA) and hydrochlorothiazide (HCT) in tablets in the presence of losartan potassium (LST). The mathematical algorithm of multivariate chromatographic calibration technique is based on the use of the linear regression equations constructed using relationship between concentration and peak area at the five-wavelength set. The algorithm of this mathematical calibration model having a simple mathematical content was briefly described. This approach is a powerful mathematical tool for an optimum chromatographic multivariate calibration and elimination of fluctuations coming from instrumental and experimental conditions. This multivariate chromatographic calibration contains reduction of multivariate linear regression functions to univariate data set. The validation of model was carried out by analyzing various synthetic binary mixtures and using the standard addition technique. Developed calibration technique was applied to the analysis of the real pharmaceutical tablets containing EA and HCT. The obtained results were compared with those obtained by classical HPLC method. It was observed that the proposed multivariate chromatographic calibration gives better results than classical HPLC.

Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

PubMed

Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F

1995-01-01

A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

PubMed

Fan, Heng; Zhu, Jian-Hua; Yao, Xue-Qing

2018-05-01

Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

Tryptophan hydroxylase type 2 variants modulate severity and outcome of addictive behaviors in Parkinson's disease.

PubMed

Cilia, Roberto; Benfante, Roberta; Asselta, Rosanna; Marabini, Laura; Cereda, Emanuele; Siri, Chiara; Pezzoli, Gianni; Goldwurm, Stefano; Fornasari, Diego

2016-08-01

Impulse control disorders and compulsive medication intake may occur in a minority of patients with Parkinson's disease (PD). We hypothesize that genetic polymorphisms associated with addiction in the general population may increase the risk for addictive behaviors also in PD. Sixteen polymorphisms in candidate genes belonging to five neurotransmitter systems (dopaminergic, catecholaminergic, serotonergic, glutamatergic, opioidergic) and the BDNF were screened in 154 PD patients with addictive behaviors and 288 PD control subjects. Multivariate analysis investigated clinical and genetic predictors of outcome (remission vs. persistence/relapse) after 1 year and at the last follow-up (5.1 ± 2.5 years). Addictive behaviors were associated with tryptophan hydroxylase type 2 (TPH2) and dopamine transporter gene variants. A subsequent analysis within the group of cases showed a robust association between TPH2 genotype and the severity of addictive behaviors, which survived Bonferroni correction for multiple testing. At multivariate analysis, TPH2 genotype resulted the strongest predictor of no remission at the last follow-up (OR[95%CI], 7.4[3.27-16.78] and 13.2[3.89-44.98] in heterozygous and homozygous carriers, respectively, p < 0.001). The extent of medication dose reduction was not a predictor. TPH2 haplotype analysis confirmed the association with more severe symptoms and lower remission rates in the short- and the long-term (p < 0.005 for all analyses). The serotonergic system is likely to be involved in the pathophysiology of addictive behaviors in PD, modulating the severity of symptoms and the rate of remission at follow-up. If confirmed in larger independent cohorts, TPH2 genotype may become a useful biomarker for the identification of at-risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease.

PubMed

Sargent, Julia; Muzzi, Ruthnea; Mukherjee, Rajat; Somarathne, Sharlene; Schranz, Katherine; Stephenson, Hannah; Connolly, David; Brodbelt, David; Fuentes, Virginia Luis

2015-03-01

To evaluate vena contracta and other echocardiographic measures of myxomatous mitral valve disease (MMVD) severity in a multivariable analysis of survival in dogs. 70 dogs diagnosed with MMVD from stored echocardiographic images that met study inclusion criteria. Left heart dimensions were measured as well as mitral regurgitant jet area/left atrial area (JAR), early mitral filling velocity (Evel), extent of mitral valve prolapse in right and left views (ProlR, ProlL), Prol indexed to aortic diameter (ProlR:Ao, ProlL:Ao), presence of a flail leaflet (FlailR, FlailL), and mitral regurgitation vena contracta diameter (VCR, VCL) indexed to aortic diameter (VCR:Ao, VCL:Ao). Follow-up from referring veterinarians was obtained by questionnaire or telephone to determine survival times. Inter- and intra-observer agreement was evaluated with Bland-Altman plots and weighted Kappa analysis. Survival was analyzed using Kaplan-Meier curves, logrank tests and Cox's proportional hazards. Logrank analysis showed VCL:Ao, VCR:Ao, FlailL, ProlR:Ao, ProlL:Ao, left ventricular internal dimension in diastole indexed to aortic diameter (LVIDD:Ao) >2.87, left atrium to aorta ratio (LA/Ao) >1.6, and Evel >1.4 m/s were predictors of cardiac mortality. In a multivariable analysis, the independent predictors of cardiac mortality were Evel >1.4 m/s [hazard ratio (HR) 5.0, 95% confidence interval (CI) 2.5-10.3], FlailL (HR 3.1, 95% CI 1.3-7.9), and ProlR:Ao (HR 2.8, 95% CI 1.3-6.3). Echocardiographic measures of mitral regurgitation severity and mitral valve pathology provide valuable prognostic information independent of chamber enlargement in dogs with MMVD. Copyright © 2014 Elsevier B.V. All rights reserved.

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Hilmersson, Katarzyna Said; Andersson, Roland

2018-01-01

To assess the expression of cancer stem cell (CSC) markers CD44, CD133 and CD24 in colon cancer liver metastases and analyse their predictive value for overall survival (OS) and disease-free survival (DFS) after liver resection. Patients operated on for colon cancer liver metastases were included. CSC marker expression was determined through immunohistochemistry analysis. OS and DFS were compared between marker-positive and marker-negative patients. Multivariate analysis was performed to select predictive variables for OS and DFS. CD133-positive patients had a worse DFS than CD133-negative patients, with a median DFS of 12 and 25 months (p=0.051). Multivariate analysis selected CD133 expression as a significant predictor for DFS. CD44 and CD24 were not found to predict OS or DFS. CD133 expression in colonic liver metastases is a negative prognostic factor for DFS after liver resection. In the future, CD133 could be used as a biomarker for risk stratification, and possibly for developing novel targeted therapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effects of Lacunar Infarctions on Cognitive Impairment in Patients with Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

PubMed Central

Choi, Jay Chol; Kang, Sa-Yoon; Kang, Ji-Hoon; Na, Hae Ri; Park, Ji-Kang

2011-01-01

Background and Purpose Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL. Methods We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)]. Results A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis. Conclusions These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL. PMID:22259617

Hyperthyroidism association with SLE, lessons from real-life data--A case-control study.

PubMed

Watad, Abdulla; Cohen, Arnon D; Comaneshter, Doron; Tekes-Manova, Dorit; Amital, Howard

2016-01-01

Despite the frequently encountered association between thyroid disease and systemic lupus erythematosus (SLE) is well known, it is of surprise that only several reports compromised of small population size support this observation. To investigate the association of comorbid SLE and hyperthyroidism. Using the database of the largest health maintenance organization (HMO) in Israel, the Clalit Health Services, we searched for the co-existence of SLE and hyperthyroidism. Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of hyperthyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 5018 patients with SLE and 25,090 age- and sex- matched controls. The prevalence of hyperthyroidism in patients with SLE was increased compared with the prevalence in controls (2.59% and 0.91%, respectively, p < 0.001). In a multivariate analysis, SLE was associated with hyperthyroidism (odds ratio 2.52, 95% confidence interval 2.028-3.137). Patients with SLE have a greater prevalence of hyperthyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of this possibility of this thyroid dysfunction.

Multivariate analysis: A statistical approach for computations

NASA Astrophysics Data System (ADS)

Michu, Sachin; Kaushik, Vandana

2014-10-01

Multivariate analysis is a type of multivariate statistical approach commonly used in, automotive diagnosis, education evaluating clusters in finance etc and more recently in the health-related professions. The objective of the paper is to provide a detailed exploratory discussion about factor analysis (FA) in image retrieval method and correlation analysis (CA) of network traffic. Image retrieval methods aim to retrieve relevant images from a collected database, based on their content. The problem is made more difficult due to the high dimension of the variable space in which the images are represented. Multivariate correlation analysis proposes an anomaly detection and analysis method based on the correlation coefficient matrix. Anomaly behaviors in the network include the various attacks on the network like DDOs attacks and network scanning.

Multivariate Cluster Analysis.

ERIC Educational Resources Information Center

McRae, Douglas J.

Procedures for grouping students into homogeneous subsets have long interested educational researchers. The research reported in this paper is an investigation of a set of objective grouping procedures based on multivariate analysis considerations. Four multivariate functions that might serve as criteria for adequate grouping are given and…

Factors predicting survival following complete surgical remission of pulmonary metastasis in osteosarcoma

PubMed Central

SALAH, SAMER; TOUBASI, SAMAR

2015-01-01

Pulmonary metastasectomy (PM) is associated with improved survival of patients with metastatic osteosarcoma; however, the factors affecting survival following achievement of complete surgical remission remain controversial. The main objective of this study was to report the outcomes and prognostic factors of osteosarcoma patients who achieved complete remission (CR) following PM. We analyzed the effect of demographic and disease-related characteristics on the overall survival (OS) of consecutive patients with metastatic osteosarcoma who were treated at a single institution and achieved CR following PM, through univariate and multivariate analyses. Between January, 2000 and August, 2013, 62 patients with metastatic osteosarcoma were treated and followed up at our institution. A total of 25 patients achieved CR following PM and were included in this analysis. The 5-year OS and disease-free survival following PM were 30 and 21%, respectively. The factors correlated with inferior OS in the univariate analysis included chondroblastic subtype, post-chemotherapy necrosis <90% in the primary tumor, metastasis detected during neoadjuvant or adjuvant chemotherapy and pathological identification of tumor cells reaching the visceral pleural surface of any of the resected nodules. In the multivariate analysis, the chondroblastic subtype was the sole independent adverse prognostic factor (HR=4.6, 95% CI: 1.0–21.3, P=0.044). Therefore, factors associated with tumor biology, including poor tumor necrosis in the primary tumor and detection of metastasis during primary chemotherapy, are associated with poor post-metastasectomy survival. In addition, chondroblastic subtype and visceral pleural involvement predicted poor prognosis in our series. PMID:25469287

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

PubMed

Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

The predictor of mortality outcome in adult patients with Ebola virus disease during the 2014-2015 outbreak in Guinea.

PubMed

Cherif, M S; Koonrungsesomboon, N; Diallo, M P; Le Gall, E; Kassé, D; Cherif, F; Koné, A; Diakité, M; Camara, F; Magassouba, N

2017-04-01

The purpose of this study was to examine the association of any demographic and clinical factors with mortality outcome among adult patients with Ebola virus disease (EVD) in Guinea. This retrospective observational study analyzed medical records of laboratory confirmed EVD adult patients during the 2014-2015 EVD outbreak in Guinea. The associations between any demographic or clinical variables and mortality outcome of EVD were assessed using univariate and multivariate logistic regression analyses. Of 2,310 EVD adult patients included for analysis, the overall case fatality rate was 68.1%. Univariate analyses identified factors possibly associated with mortality outcome, including patient age (p < 0.001), history of visiting or close contact with a suspected or confirmed EVD patient (p = 0.035), and seven clinical symptoms on admission, i.e., fever (p = 0.003), hiccups (p < 0.001), vomiting (p = 0.003), diarrhea (p < 0.001), cough (p = 0.001), sore throat (p = 0.016), and unexplained bleeding (p = 0.021). The multivariate analysis showed that patient age was independently associated with mortality outcome of EVD (OR = 1.06; 95%CI = 1.03-1.09; p < 0.001), while none the of clinical symptoms on admission were significantly associated with the mortality outcome. Our analysis indicates that older age was the only independent factor associated with death among EVD adult patients in Guinea. This suggests that older EVD patients should receive intensive medical care and be carefully monitored.

Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.

PubMed

Keohane, Denis; Schwartz, Jeffrey; Gundapaneni, Balarama; Stewart, Michelle; Amass, Leslie

2017-03-01

Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial. Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques. Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect. These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP. NCT00409175.

Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea

PubMed Central

Zulu, Isaac; Hassan, Ghaniah; Njobvu RN, Lungowe; Dhaliwal, Winnie; Sianongo, Sandie; Kelly, Paul

2008-01-01

Background Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality. Methods Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-γ and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up. Results Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-γ, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis. Conclusion High serum concentrations of TNFR p55, IFN-γ, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-γ and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa. PMID:19014537

Comparative study of the clinical presentation of Legionella pneumonia and other community-acquired pneumonias.

PubMed

Sopena, N; Sabrià-Leal, M; Pedro-Botet, M L; Padilla, E; Dominguez, J; Morera, J; Tudela, P

1998-05-01

The aim of this study was to compare the clinical, biological, and radiologic features of presentation in the emergency ward of community-acquired pneumonia (CAP) by Legionella pneumophila (LP) and other community-acquired bacterial pneumonias to help in early diagnosis of CAP by LP. Three hundred ninety-two patients with CAP were studied prospectively in the emergency department of a 600-bed university hospital. Univariate and multivariate analyses were performed to compare epidemiologic and demographic data and clinical, analytical, and radiologic features of presentation in 48 patients with CAP by LP and 125 patients with CAP by other bacterial etiology (68 by Streptococcus pneumoniae, 41 by Chlamydia pneumoniae, 5 by Mycoplasma pneumoniae, 4 by Coxiella burnetii, 3 by Pseudomonas aeruginosa, 2 by Haemophilus influenzae, and 2 by Nocardia species. Univariate analysis showed that CAP by LP was more frequent in middle-aged, male healthy (but alcohol drinking) patients than CAP by other etiology. Moreover, the lack of response to previous beta-lactamic drugs, headache, diarrhea, severe hyponatremia, and elevation in serum creatine kinase (CK) levels on presentation were more frequent in CAP by LP, while cough, expectoration, and thoracic pain were more frequent in CAP by other bacterial etiology. However, multivariate analysis only confirmed these differences with respect to lack of underlying disease, diarrhea, and elevation in the CK level. We conclude that detailed analysis of features of presentation of CAP allows suspicion of Legionnaire's disease in the emergency department. The initiation of antibiotic treatment, including a macrolide, and the performance of rapid diagnostic techniques are mandatory in these cases.

Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

PubMed

Jin, Lei; Gao, Yufeng; Ye, Jun; Zou, Guizhou; Li, Xu

2017-09-01

The red blood cell distribution width (RDW) is increased in chronic liver disease, but its clinical significance in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is still unclear. The aim of the present study was to investigate the clinical significance of RDW in HBV-ACLF patients. The medical records of HBV-ACLF patients who were admitted to The Second Affiliated Hospital of Anhui Medical University between April 2012 and December 2015 were retrospectively reviewed. Correlations between RDW, neutrophil lymphocyte ratio (NLR), and the model for end-stage liver disease (MELD) scores were analyzed using the Spearman's approach. Multivariable stepwise logistic regression test was used to evaluate independent clinical parameters predicting 3-month mortality of HBV-ACLF patients. The association between RDW and hospitalization outcome was estimated by receiver operating curve (ROC) analysis. Patient survival was estimated by Kaplan-Meier analysis and subsequently compared by log-rank test. Sixty-two HBV-ACLF patients and sixty CHB patients were enrolled. RDW were increased in HBVACLF patients and positively correlated with the NLR as well as MELD scores. Multivariate analysis demonstrated that RDW value was an independent predictor for mortality. RDW had an area under the ROC of 0.799 in predicting 3-month mortality of HBV-ACLF patients. Patients with HBV-ACLF who had RDW > 17% showed significantly poorer survival than those who had RDW ≤ 17%. RDW values are significantly increased in patients with HBV-ACLF. Moreover, RDW values are an independent predicting factor for an in-hospital mortality in patients with HBV-ACLF.

Optimal Cutoff Values of WHO-HPQ Presenteeism Scores by ROC Analysis for Preventing Mental Sickness Absence in Japanese Prospective Cohort

PubMed Central

Suzuki, Tomoko; Miyaki, Koichi; Sasaki, Yasuharu; Song, Yixuan; Tsutsumi, Akizumi; Kawakami, Norito; Shimazu, Akihito; Takahashi, Masaya; Inoue, Akiomi; Kurioka, Sumiko; Shimbo, Takuro

2014-01-01

Objectives Sickness absence due to mental disease in the workplace has become a global public health problem. Previous studies report that sickness presenteeism is associated with sickness absence. We aimed to determine optimal cutoff scores for presenteeism in the screening of the future absences due to mental disease. Methods A prospective study of 2195 Japanese employees from all areas of Japan was conducted. Presenteeism and depression were measured by the validated Japanese version of the World Health Organization Health and Work Performance Questionnaire (WHO-HPQ) and K6 scale, respectively. Absence due to mental disease across a 2-year follow-up was surveyed using medical certificates obtained for work absence. Socioeconomic status was measured via a self-administered questionnaire. Receiver operating curve (ROC) analysis was used to determine optimal cutoff scores for absolute and relative presenteeism in relation to the area under the curve (AUC), sensitivity, and specificity. Results The AUC values for absolute and relative presenteeism were 0.708 (95% CI, 0.618–0.797) and 0.646 (95% CI, 0.546–0.746), respectively. Optimal cutoff scores of absolute and relative presenteeism were 40 and 0.8, respectively. With multivariate adjustment, cohort participants with our proposal cutoff scores for absolute and relative presenteeism were significantly more likely to be absent due to mental disease (OR = 4.85, 95% CI: 2.20–10.73 and OR = 5.37, 95% CI: 2.42–11.93, respectively). The inclusion or exclusion of depressive symptoms (K6≥13) at baseline in the multivariate adjustment did not influence the results. Conclusions Our proposed optimal cutoff scores of absolute and relative presenteeism are 40 and 0.8, respectively. Participants who scored worse than the cutoff scores for presenteeism were significantly more likely to be absent in future because of mental disease. Our findings suggest that the utility of presenteeism in the screening of sickness absence due to mental disease would help prevent such an absence. PMID:25340520

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

PubMed

Vuitton, Lucine; Jacquin, Elise; Parmentier, Anne-Laure; Crochet, Elise; Fein, Francine; Dupont-Gossart, Anne-Claire; Plastaras, Laurianne; Bretagne, Charles-Henri; Mauny, Frédéric; Koch, Stéphane; Prétet, Jean-Luc; Mougin, Christiane; Valmary-Degano, Séverine

2018-03-15

The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Postoperative Outcomes in Graves' Disease Patients: Results from the Nationwide Inpatient Sample Database.

PubMed

Rubio, Gustavo A; Koru-Sengul, Tulay; Vaghaiwalla, Tanaz M; Parikh, Punam P; Farra, Josefina C; Lew, John I

2017-06-01

Current surgical indications for Graves' disease include intractability to medical and/or radioablative therapy, compressive symptoms, and worsening ophthalmopathy. Total thyroidectomy for Graves' disease may be technically challenging and lead to untoward perioperative outcomes. This study examines outcomes in patients with Graves' disease who underwent total thyroidectomy and assesses its safety for this patient population. A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database from 2006 to 2011. Total thyroidectomy performed in patients with Graves' disease, benign multinodular goiter (MNG), and thyroid cancer was identified. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-square, one-way analysis of variance, and risk-adjusted multivariable logistic regression were performed. Of 215,068 patients who underwent total thyroidectomy during the study period, 11,205 (5.2%) had Graves' disease, 110,124 (51.2%) MNG, and 93,739 (43.6%) thyroid malignancy. Patients with Graves' disease were younger than MNG and thyroid cancer patients (M age  = 42.8 years vs. 55.5 and 51.0 years; p < 0.01). The Graves' disease group included a higher proportion of women (p < 0.01) and nonwhites (p < 0.01). Postoperatively, Graves' patients had significantly higher rates of hypocalcemia (12.4% vs. 7.3% and 10.3%; p < 0.01), hematomas requiring reoperation (0.7% vs. 0.4% and 0.4%; p < 0.01), and longer mean hospital stay (2.7 days vs. 2.4 and 2.2 days; p < 0.01) compared to MNG and thyroid cancer patients, respectively. On risk-adjusted multivariate logistic regression, Graves' disease was independently associated with a higher risk of vocal-cord paralysis (odds ratio [OR] = 1.36 [confidence interval (CI) 1.08-1.69]), tracheostomy (OR = 1.35 [CI 1.1-1.67]), postoperative hypocalcemia (OR = 1.65 [CI 1.54-1.77]), and hematoma requiring reoperation (OR = 2.79 [CI 2.16-3.62]) compared to MNG patients. High-volume centers for total thyroidectomy were independently associated with lower risk of postoperative complications, including in patients with Graves' disease. Despite low overall morbidity following total thyroidectomy, Graves' disease patients are at increased risk of postoperative complications, including bleeding, vocal-cord paralysis, tracheostomy, and hypocalcemia. These risks appear to be lower when performed at high-volume centers, and thus referral to these centers should be considered. Total thyroidectomy may therefore be a safe treatment option for appropriately selected patients with Graves' disease when performed by experienced surgeons.

Infrared micro-spectroscopic studies of epithelial cells

PubMed Central

Romeo, Melissa; Mohlenhoff, Brian; Jennings, Michael; Diem, Max

2009-01-01

We report results from a study of human and canine mucosal cells, investigated by infrared micro-spectroscopy, and analyzed by methods of multivariate statistics. We demonstrate that the infrared spectra of individual cells are sensitive to the stage of maturation, and that a distinction between healthy and diseased cells will be possible. Since this report is written for an audience not familiar with infrared micro-spectroscopy, a short introduction into this field is presented along with a summary of principal component analysis. PMID:16797481

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Sex-based Prognostic Implications of Nonobstructive Coronary Artery Disease: Results from the International Multicenter CONFIRM Study

PubMed Central

Taylor, Carolyn M.; Gransar, Heidi; Shaw, Leslee J.; Ahmadi, Amir; Thompson, Angus; Humphries, Karin; Berman, Daniel S.; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Fillippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Chow, Benjamin J. W.; Cury, Ricardo C.; Delago, Augustin J.; Dunning, Allison L.; Feuchtner, Gudrun M.; Hadamitzky, Martin; Kaufmann, Philipp A.; Lin, Fay Y.; Chinnaiyan, Kavitha M.; Maffei, Erica; Raff, Gilbert L.; Villines, Todd C.; Gomez, Millie J.; Min, James K.

2014-01-01

Purpose To determine the clinical outcomes of women and men with nonobstructive coronary artery disease (CADcoronary artery disease) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CADcoronary artery disease risk factors, angina typicality, and CADcoronary artery disease extent and distribution. Materials and Methods Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CADcoronary artery disease or nonobstructive (<50% stenosis) CADcoronary artery disease were examined. Men and women were propensity matched for age, CADcoronary artery disease risk factors, angina typicality, and CADcoronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CADcoronary artery disease presence and extent were related to incident major adverse cardiovascular events (MACEmajor adverse cardiovascular events), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. Results At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACEmajor adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACEmajor adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CADcoronary artery disease was associated with similarly increased MACEmajor adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval {CIconfidence interval}: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CIconfidence interval: 1.07, 2.93], P = .03). Conclusion When matched for age, CADcoronary artery disease risk factors, angina typicality, and nonobstructive CADcoronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028784

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

PubMed

Leipsic, Jonathon; Taylor, Carolyn M; Gransar, Heidi; Shaw, Leslee J; Ahmadi, Amir; Thompson, Angus; Humphries, Karin; Berman, Daniel S; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J; Cademartiri, Fillippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chow, Benjamin J W; Cury, Ricardo C; Delago, Augustin J; Dunning, Allison L; Feuchtner, Gudrun M; Hadamitzky, Martin; Kaufmann, Philipp A; Lin, Fay Y; Chinnaiyan, Kavitha M; Maffei, Erica; Raff, Gilbert L; Villines, Todd C; Gomez, Millie J; Min, James K

2014-11-01

To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.

PubMed

Teo, Koon K; Goldstein, Larry B; Chaitman, Bernard R; Grant, Shannon; Weintraub, William S; Anderson, David C; Sila, Cathy A; Cruz-Flores, Salvador; Padley, Robert J; Kostuk, William J; Boden, William E

2013-10-01

In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN. This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk. There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063). Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk. http://www.clinicaltrials.gov. Unique identifier: NCT00120289.

Positron emission tomography–computed tomography predictors of progression after DA-R-EPOCH for PMBCL

PubMed Central

Ng, Andrea K.; Dabaja, Bouthaina S.; Milgrom, Sarah A.; Gunther, Jillian R.; Fuller, C. David; Smith, Grace L.; Abou Yehia, Zeinab; Qiao, Wei; Wogan, Christine F.; Akhtari, Mani; Mawlawi, Osama; Medeiros, L. Jeffrey; Chuang, Hubert H.; Martin-Doyle, William; Armand, Philippe; LaCasce, Ann S.; Oki, Yasuhiro; Fanale, Michelle; Westin, Jason; Neelapu, Sattva; Nastoupil, Loretta

2018-01-01

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18F]fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning–derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance (P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis (P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression. PMID:29895624

Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis

PubMed Central

Wood, Marnie J; Powell, Lawrie W; Dixon, Jeannette L; Subramaniam, V Nathan; Ramm, Grant A

2013-01-01

AIM: To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis. METHODS: A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied, with all subjects having liver biopsy data and DNA available for testing. This study assessed the association of eight single nucleotide polymorphisms (SNPs) in a total of six genes including toll-like receptor 4 (TLR4), transforming growth factor-beta (TGF-β), oxoguanine DNA glycosylase, monocyte chemoattractant protein 1, chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity. Genotyping was performed using high resolution melt analysis and sequencing. The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration. RESULTS: There were significant associations between the cofactors of male gender (P = 0.0001), increasing age (P = 0.006), alcohol consumption (P = 0.0001), steatosis (P = 0.03), hepatic iron concentration (P < 0.0001) and the presence of hepatic fibrosis. Of the candidate gene polymorphisms studied, none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors. We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied. Importantly, in this large, well characterised cohort of patients there was no association between SNPs for TGF-β or TLR4 and the presence of fibrosis, cirrhosis or increasing fibrosis stage in multivariate analysis. CONCLUSION: In our large, well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis. PMID:24409064

Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis.

PubMed

Wood, Marnie J; Powell, Lawrie W; Dixon, Jeannette L; Subramaniam, V Nathan; Ramm, Grant A

2013-12-28

To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis. A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied, with all subjects having liver biopsy data and DNA available for testing. This study assessed the association of eight single nucleotide polymorphisms (SNPs) in a total of six genes including toll-like receptor 4 (TLR4), transforming growth factor-beta (TGF-β), oxoguanine DNA glycosylase, monocyte chemoattractant protein 1, chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity. Genotyping was performed using high resolution melt analysis and sequencing. The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration. There were significant associations between the cofactors of male gender (P = 0.0001), increasing age (P = 0.006), alcohol consumption (P = 0.0001), steatosis (P = 0.03), hepatic iron concentration (P < 0.0001) and the presence of hepatic fibrosis. Of the candidate gene polymorphisms studied, none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors. We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied. Importantly, in this large, well characterised cohort of patients there was no association between SNPs for TGF-β or TLR4 and the presence of fibrosis, cirrhosis or increasing fibrosis stage in multivariate analysis. In our large, well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.

Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL.

PubMed

Pinnix, Chelsea C; Ng, Andrea K; Dabaja, Bouthaina S; Milgrom, Sarah A; Gunther, Jillian R; Fuller, C David; Smith, Grace L; Abou Yehia, Zeinab; Qiao, Wei; Wogan, Christine F; Akhtari, Mani; Mawlawi, Osama; Medeiros, L Jeffrey; Chuang, Hubert H; Martin-Doyle, William; Armand, Philippe; LaCasce, Ann S; Oki, Yasuhiro; Fanale, Michelle; Westin, Jason; Neelapu, Sattva; Nastoupil, Loretta

2018-06-12

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [ 18 F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance ( P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis ( P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression. © 2018 by The American Society of Hematology.

Different MR features for differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma according to tumor size.

PubMed

Ni, Ting; Shang, Xiao-Sha; Wang, Wen-Tao; Hu, Xin-Xing; Zeng, Meng-Su; Rao, Sheng-Xiang

2018-06-05

To identify reliable magnetic resonance (MR) features for distinguishing mass-forming type of intrahepatic cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) based on tumor size. This retrospective study included 395 patients with pathologically confirmed IMCCs (n = 180) and HCCs (n = 215) who underwent pre-operative contrast-enhanced MRI including diffusion-weighted imaging (DWI). MR features were evaluated and clinical data were also recorded. All the characteristics were compared in small (≤3 cm) and large tumor (>3 cm) groups by univariate analysis and subsequently calculated by multivariable logistic regression analysis. Multivariable analysis revealed that rim arterial phase hyperenhancement [odds ratios (ORs) = 13.16], biliary dilation (OR = 23.42) and CA19-9 (OR = 21.45) were significant predictors of large IMCCs (n = 138), and washout appearance (OR = 0.036), enhancing capsule appearance (OR = 0.039), fat in mass (OR = 0.057), chronic liver disease (OR = 0.088) and alpha fetoprotein (OR = 0.019) were more frequently found in large HCCs (n = 143). For small IMCCs (n = 42) and HCCs (n = 72), rim arterial phase hyperenhancement (OR = 9.68), target appearance at DWI (OR = 12.51), alpha fetoprotein (OR = 0.12) and sex (OR = 0.20) were independent predictors in multivariate analysis. Valuable MR features and clinical factors varied for differential diagnosis of IMCCs and HCCs according to tumor size. Advances in knowledge: MR features for differential diagnosis of large IMCC and HCC (>3 cm) are in keeping with that recommended by LI-RADS. However, for small IMCCs and HCCs (≤3 cm), only rim enhancement on arterial phase and target appearance at DWI are reliable predictors.

Characteristics of foodborne outbreaks in which use of analytical epidemiological studies contributed to identification of suspected vehicles, European Union, 2007 to 2011.

PubMed

Schlinkmann, K M; Razum, O; Werber, D

2017-04-01

Foodborne disease outbreaks (FBDOs) occur frequently in Europe. Employing analytical epidemiological study designs increases the likelihood of identifying the suspected vehicle(s), but these studies are rarely applied in FBDO investigations. We used multivariable binary logistic regression analysis to identify characteristics of investigated FBDOs reported to the European Food Safety Authority (2007-2011) that were associated with analytical epidemiological evidence (compared to evidence from microbiological investigations/descriptive epidemiology only). The analysis was restricted to FBDO investigations, where the evidence for the suspected vehicle was considered 'strong', i.e. convincing. The presence of analytical epidemiological evidence was reported in 2012 (50%) of these 4038 outbreaks. In multivariable analysis, increasing outbreak size, number of hospitalizations, causative (i.e. aetiological) agent (whether identified and, if so, which one), and the setting in which these outbreaks occurred (e.g. geographically dispersed outbreaks) were independently associated with presence of analytical evidence. The number of investigations with reported analytical epidemiological evidence was unexpectedly high, likely indicating the need for quality assurance within the European Union foodborne outbreak reporting system, and warranting cautious interpretation of our findings. This first analysis of evidence implicating a food vehicle in FBDOs may help to inform public health authorities on when to use analytical epidemiological study designs.

Comparative forensic soil analysis of New Jersey state parks using a combination of simple techniques with multivariate statistics.

PubMed

Bonetti, Jennifer; Quarino, Lawrence

2014-05-01

This study has shown that the combination of simple techniques with the use of multivariate statistics offers the potential for the comparative analysis of soil samples. Five samples were obtained from each of twelve state parks across New Jersey in both the summer and fall seasons. Each sample was examined using particle-size distribution, pH analysis in both water and 1 M CaCl2 , and a loss on ignition technique. Data from each of the techniques were combined, and principal component analysis (PCA) and canonical discriminant analysis (CDA) were used for multivariate data transformation. Samples from different locations could be visually differentiated from one another using these multivariate plots. Hold-one-out cross-validation analysis showed error rates as low as 3.33%. Ten blind study samples were analyzed resulting in no misclassifications using Mahalanobis distance calculations and visual examinations of multivariate plots. Seasonal variation was minimal between corresponding samples, suggesting potential success in forensic applications. © 2014 American Academy of Forensic Sciences.

[Factors associated with mortality in Legionnaires' disease, France, 2002-2004].

PubMed

Poupard, M; Campèse, C; Bernillon, P; Che, D

2007-06-01

Risk factors for Legionnaires' disease are well known (older age, smoking, or immunosuppression), however, the factors associated with mortality are less documented. A retrospective analysis based on cases notified between 2002 and 2004 was conducted in France to identify these factors. Cases were identified through mandatory notifications sent to the Institut de veille sanitaire, France. Factors associated with mortality were identified using a logistic regression analysis. Three thousand two hundred sixty-seven cases of Legionnaire's disease were notified during the study period and the evolution was documented for 85% of the cases (2.791). Three hundred seventy-seven deaths (13.5%) were notified. 72.5% of the patients were men and the median age was 61. The multivariate analysis applied to patients under 60 years revealed that cancer or hemopathy (OR=6.4 CI95% 3.6-11.2), underlying renal disease (OR=3.2 CI95% 1.0-9.9), or alcohol abuse (OR=2.2 CI95% 1.1-4.4) were associated with mortality. For older patients (>60 years) factors linked to mortality were: cancer/hemopathy (OR=1.8 CI95% 1.2-2.6), underlying renal disease (OR=3 CI95% 1.4-6.4), underlying cardiac disease (OR=2.4 CI95% 1.4-4), alcohol abuse (OR=2.4 CI95% 1.2-5.2), immunosuppression (OR=1.7 CI95% 1.1-2.6), nosocomial acquisition of the disease (OR=2.0 CI95% 1.3-3), or infection acquired in nursing home residents (OR=2.4 IC 95% 1.6-3.6). These preliminary results further describe Legionnaires' disease and its mortality. However, they should be confirmed by carefully conducted prospective analysis. The description of LD patients at high risk of death will contribute to better prevention measures.

Predictive features of chronic kidney disease in atypical haemolytic uremic syndrome

PubMed Central

Jamme, Matthieu; Raimbourg, Quentin; Chauveau, Dominique; Seguin, Amélie; Presne, Claire; Perez, Pierre; Gobert, Pierre; Wynckel, Alain; Provôt, François; Delmas, Yahsou; Mousson, Christiane; Servais, Aude; Vrigneaud, Laurence; Veyradier, Agnès

2017-01-01

Chronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation, this model may assist in clinical decision making. PMID:28542627

Arteriovenous fistula maturation in patients with permanent access created prior to or after hemodialysis initiation.

PubMed

Duque, Juan C; Martinez, Laisel; Tabbara, Marwan; Dvorquez, Denise; Mehandru, Sushil K; Asif, Arif; Vazquez-Padron, Roberto I; Salman, Loay H

2017-05-15

Multiple factors and comorbidities have been implicated in the ability of arteriovenous fistulas (AVF) to mature, including vessel anatomy, advanced age, and the presence of coronary artery disease or peripheral vascular disease. However, little is known about the role of uremia on AVF primary failure. In this study, we attempt to evaluate the effect of uremia on AVF maturation by comparing AVF outcomes between pre-dialysis chronic kidney disease (CKD) stage five patients and those who had their AVF created after hemodialysis (HD) initiation. We included 612 patients who underwent AVF creation between 2003 and 2015 at the University of Miami Hospital and Jackson Memorial Hospital. Effects of uremia on primary failure were evaluated using univariate statistical comparisons and multivariate logistic regression analyses. Primary failure occurred in 28.1% and 26.3% of patients with an AVF created prior to or after HD initiation, respectively (p = 0.73). The time of HD initiation was not associated with AVF maturation in multivariate logistic regression analysis (p = 0.57). In addition, pre-operative blood urea nitrogen (p = 0.78), estimated glomerular filtration rate (p = 0.66), and serum creatinine levels (p = 0.14) were not associated with AVF primary failure in pre-dialysis patients. Our results show that clearance of uremia with regular HD treatments prior to AVF creation does not improve the frequency of vascular access maturation.

Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

PubMed Central

Jackson, Dan; White, Ian R; Riley, Richard D

2012-01-01

Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I2, which we call . We also provide a multivariate H2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22763950

Ultrasound measurement of peripheral endothelial dysfunction in type 2 diabetic patients: correlation with risk factors

PubMed Central

Bosevski, Marijan; Georgievska-Ismail, Ljubica

2010-01-01

The purpose of the study was to assess the endothelial dysfunction (ED) in type 2 diabetic patients ultrasonographicaly and estimate the correlation of ED with glycemia and other cardio-metabolic risk factors. 171 patient (age 60,0 + 8,5 years) with diagnosed type 2 diabetes and coronary artery disease (CAD) were randomly included in a cross sectional study. B-mode ultrasound system with a linear transducer of 7.5 MHz was used for evaluation of flow-mediated vasodilation in brachial artery (FMV). FMV was presented as a change of brachial artery diameter at rest and after limb ischemia, previously provoked by cuff inflation. Peripheral ED was found in 77,2% (132 patients). Multivariate logistic regression model defined: age (OR 1,071, 95% CI 1,003 1,143) and plasma cholesterol (OR 4,083 95%CI 1,080 17,017) as determinants for ED. Linear multivariate analysis presented duration of diabetes (Beta 0,173, Sig 0,024), and glycemia (Beta 0,132, Sig 0,044) to be associated independently with FMV value. Estimated factors influencing FMV might be potential therapeutic targets for presented endothelial dysfunction in type 2 diabetic patients with coronary artery disease. PMID:20507285

Multivariate inference of pathway activity in host immunity and response to therapeutics

PubMed Central

Goel, Gautam; Conway, Kara L.; Jaeger, Martin; Netea, Mihai G.; Xavier, Ramnik J.

2014-01-01

Developing a quantitative view of how biological pathways are regulated in response to environmental factors is central for understanding of disease phenotypes. We present a computational framework, named Multivariate Inference of Pathway Activity (MIPA), which quantifies degree of activity induced in a biological pathway by computing five distinct measures from transcriptomic profiles of its member genes. Statistical significance of inferred activity is examined using multiple independent self-contained tests followed by a competitive analysis. The method incorporates a new algorithm to identify a subset of genes that may regulate the extent of activity induced in a pathway. We present an in-depth evaluation of specificity, robustness, and reproducibility of our method. We benchmarked MIPA's false positive rate at less than 1%. Using transcriptomic profiles representing distinct physiological and disease states, we illustrate applicability of our method in (i) identifying gene–gene interactions in autophagy-dependent response to Salmonella infection, (ii) uncovering gene–environment interactions in host response to bacterial and viral pathogens and (iii) identifying driver genes and processes that contribute to wound healing and response to anti-TNFα therapy. We provide relevant experimental validation that corroborates the accuracy and advantage of our method. PMID:25147207

[Negative prognostic impact of female gender on oncological outcomes following radical cystectomy].

PubMed

Dabi, Y; Rouscoff, Y; Delongchamps, N B; Sibony, M; Saighi, D; Zerbib, M; Peyraumore, M; Xylinas, E

2016-02-01

To confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy. We conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer. Impact of gender on recurrence rate, specific and non-specific mortality rate were evaluated using Cox regression models in univariate and multivariate analysis. We collected data on 553 males (78.9%) and 148 females (21.1%) between 1998 and 2011. Both groups were comparable at inclusion regarding age, pathologic stage, nodal status and lymphovascular invasion. Mean follow-up time was 45 months (interquartile 23-73) and by that time, 163 patients (23.3%) had recurrence of their tumor and 127 (18.1%) died from their disease. In multivariable Cox regression analyses, female gender was independently associated with disease recurrence (RR: 1.73; 95% CI 1.22-2.47; P=0.02) and cancer-specific mortality (RR=2.50, 95% CI=1.71-3.68; P<0.001). We confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Analyzing Multiple Outcomes in Clinical Research Using Multivariate Multilevel Models

PubMed Central

Baldwin, Scott A.; Imel, Zac E.; Braithwaite, Scott R.; Atkins, David C.

2014-01-01

Objective Multilevel models have become a standard data analysis approach in intervention research. Although the vast majority of intervention studies involve multiple outcome measures, few studies use multivariate analysis methods. The authors discuss multivariate extensions to the multilevel model that can be used by psychotherapy researchers. Method and Results Using simulated longitudinal treatment data, the authors show how multivariate models extend common univariate growth models and how the multivariate model can be used to examine multivariate hypotheses involving fixed effects (e.g., does the size of the treatment effect differ across outcomes?) and random effects (e.g., is change in one outcome related to change in the other?). An online supplemental appendix provides annotated computer code and simulated example data for implementing a multivariate model. Conclusions Multivariate multilevel models are flexible, powerful models that can enhance clinical research. PMID:24491071

A prospective study of periodontal disease and pancreatic cancer in US male health professionals.

PubMed

Michaud, Dominique S; Joshipura, Kaumudi; Giovannucci, Edward; Fuchs, Charles S

2007-01-17

Two previous cohort studies reported positive associations between tooth loss or periodontitis and pancreatic cancer risk. Data on periodontal disease were obtained at baseline and every other year thereafter in a cohort of 51,529 male health professionals aged 40-75 years. A total of 216 patients were diagnosed with incident pancreatic cancer during 16 years of follow-up. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models controlling for potential confounders, including detailed smoking history. All statistical tests were two-sided. Compared with no periodontal disease, history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline number of natural teeth and cumulative tooth loss during follow-up were not strongly associated with pancreatic cancer. The association between periodontal disease and increased risk of pancreatic cancer may occur through plausible biologic mechanisms, but confirmation of this association is necessary.

Hypertension Control in Adults With Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results From the Trial Evaluating Cardiovascular Outcomes With Sitagliptin.

PubMed

Navar, Ann Marie; Gallup, Dianne S; Lokhnygina, Yuliya; Green, Jennifer B; McGuire, Darren K; Armstrong, Paul W; Buse, John B; Engel, Samuel S; Lachin, John M; Standl, Eberhard; Van de Werf, Frans; Holman, Rury R; Peterson, Eric D

2017-11-01

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function. © 2017 American Heart Association, Inc.

Phyllodes Tumor of the Breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belkacemi, Yazid; University of Lille II, Lille; Bousquet, Guilhem

Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapymore » (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size

Predictors of Residual Disease after Unplanned Excision of Soft Tissue Sarcomas

PubMed Central

Gingrich, Alicia A.; Elias, Alexandra; Michael Lee, Chia-Yuan; Nakache, Yves-Paul N.; Li, Chin-Shang; Shah, Dhruvil R.; Boutin, Robert D.; Canter, Robert J.

2016-01-01

Background Unplanned excision of soft tissue sarcomas (STS) is an important quality of care issue given the morbidity related to tumor bed excision. Since not all patients harbor residual disease at the time of re-excision, we sought to determine predictors of residual STS following unplanned excision. Methods We identified 76 patients from a prospective database (1/1/2008 – 9/30/2014) who received a diagnosis of primary STS following unplanned excision on the trunk or extremities. We used univariable and multivariable analyses to evaluate predictors of residual STS as the primary endpoint. We calculated the sensitivity/specificity and accuracy of interval magnetic resonance imaging (MRI) to predict residual sarcoma at re-excision. Results Mean age was 52 years, and 63.2% were male. 50% had fragmented unplanned excision. Among patients undergoing re-excision, residual STS was identified in 70%. On univariable analysis, MRI showing gross disease and fragmented excision were significant predictors of residual STS (OR 10.59, 95% CI 2.14–52.49, P=0.004 and OR 3.61, 95% CI 1.09–11.94, P=0.035, respectively). On multivariable analysis, tumor size predicted distant recurrence and overall survival. When we combined equivocal and positive MRI, the sensitivity and specificity of MRI for predicting residual STS were 86.7% (95% CI 73.2–95.0%) and 57.9% (95% CI 33.5–79.8%), with an overall accuracy of 78.1% (95% CI 66.0–87.5%). Conclusions 70% of patients undergoing repeat excision after unplanned excision of STS harbor residual sarcoma. Although interval MRI and fragmented excision appear to be the most significant predictors of residual STS, the accuracy of MRI remains modest, especially given the incidence of equivocal MRI. PMID:27993214

Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, Kristin A., E-mail: kristin.higgins@duke.edu; Chino, Junzo P.; Berry, Mark

2012-06-01

Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meiermore » method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.« less

Emergence of sporadic non-clustered cases of hospital-associated listeriosis among immunocompromised adults in southern Taiwan from 1992 to 2013: effect of precipitating immunosuppressive agents.

PubMed

Lee, Chun-Yuan; Tsai, Hung-Chin; Kunin, Calvin M; Lee, Susan Shin-Jung; Wu, Kuan-Sheng; Chen, Yao-Shen

2014-03-19

Sporadic non-clustered hospital-associated listeriosis is an emerging infectious disease in immunocompromised hosts. The current study was designed to determine the impact of long-term and precipitating immunosuppressive agents and underlying diseases on triggering the expression of the disease, and to compare the clinical features and outcome of hospital-associated and community-associated listeriosis. We reviewed the medical records of all patients with Listeria monocytogenes isolated from sterile body sites at a large medical center in southern Taiwan during 1992-2013. Non-clustered cases were defined as those unrelated to any other in time or place. Multivariable regression analysis was used to determine factors associated with prognosis. Thirty-five non-clustered cases of listeriosis were identified. Twelve (34.2%) were hospital-associated, and 23 (65.7%) were community-associated. The 60-day mortality was significantly greater in hospital-associated than in community-associated cases (66.7% vs. 17.4%, p = 0.007). Significantly more hospital-associated than community-associated cases were treated with a precipitating immunosuppressive agent within 4 weeks prior to onset of listeriosis (91.7% vs. 4.3%, respectively p < 0.001). The median period from the start of precipitating immunosuppressive treatment to the onset of listeriosis-related symptoms was 12 days (range, 4-27 days) in 11 of the 12 hospital-associated cases. In the multivariable analysis, APACHE II score >21 (p = 0.04) and receipt of precipitating immunosuppressive therapy (p = 0.02) were independent risk factors for 60-day mortality. Sporadic non-clustered hospital-associated listeriosis needs to be considered in the differential diagnosis of sepsis in immunocompromised patients, particularly in those treated with new or increased doses of immunosuppressive agents.

Association of Socioeconomic Status Measured by Education and Risk Factors for Carotid Atherosclerosis: Cross-sectional Study

PubMed Central

Maksimović, Miloš Ž.; Vlajinac, Hristina D.; Radak, Đorđe J.; Maksimović, Jadranka M.; Marinković, Jelena M.; Jorga, Jagoda B.

2008-01-01

Aim To investigate the association between socioeconomic status and metabolic syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory markers as risk factors for carotid atherosclerotic disease. Methods This cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia, during the period 2006-2007. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education – low (≤primary school), medium (secondary school), and high (university education). In the analysis, univariate and multivariate logistic regressions were used. Results Multivariate analysis showed that low education was significantly positively associated with female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81), increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR, 0.42; 95% CI, 0.23-0.75). Medium education was significantly positively associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97; 95% CI, 0.94-0.99). Conclusion Increased triglycerides and hsCRP in people with low and medium education, and high prevalence of metabolic syndrome, its components and inflammatory markers in all study participants, suggest that regular health check-up, especially for those with lower education, may be useful in early detection and treatment of any abnormality that can be associated with cardiovascular disease. PMID:19090608

Ethnic Differences in the Risk Factors and Severity of Coronary Artery Disease: a Patient-Based Study in Iran.

PubMed

Abbasi, Seyed Hesameddin; Sundin, Örjan; Jalali, Arash; Soares, Joaquim; Macassa, Gloria

2018-06-01

Diverse ethnic groups may differ regarding the risk factors and severity of coronary artery disease (CAD). This study sought to assess the association between ethnicity and CAD risk and severity in six major Iranian ethnic groups. In this study, 20,165 documented coronary artery disease patients who underwent coronary angiography at a tertiary referral heart center were recruited. The demographic, laboratory, clinical, and risk factor data of all the patients were retrieved. The Gensini score (an indicator of CAD severity) was calculated for all, and the risk factors and severity of CAD were compared between the ethnical groups, using adjusted standardized residuals, Kruskal-Wallis test, and multivariable regression analysis. The mean age of the participants (14,131 [70.1%] men and 6034 [29.9%] women) was 60.7 ± 10.8 years. The Fars (8.7%) and Gilak (8.6%) ethnic groups had the highest prevalence of ≥4 simultaneous risk factors. The mean Gensini score was the highest for the Gilaks (77.1 ± 55.9) and the lowest among the Lors (67.5 ± 52.8). The multivariable regression analysis showed that the Gilaks had the worst severity (β 0.056, 95% CI 0.009 to 0.102; P = 0.018), followed by the Torks (β 0.032, 95% CI 0.005 to 0.059; P = 0.020). Meanwhile, the Lors showed the lowest severity (β -0.087, 95% CI -0.146 to -0.027; P = 0.004). This study found that there was heterogeneity in CAD severity and a diverse distribution in its well-known traditional risk factors among major Iranian ethnic groups.

The risk of carotid stenosis in head and neck cancer patients after radiation therapy.

PubMed

Carpenter, David J; Mowery, Yvonne M; Broadwater, Gloria; Rodrigues, Anna; Wisdom, Amy J; Dorth, Jennifer A; Patel, Pretesh R; Shortell, Cynthia K; Clough, Robert; Brizel, David M

2018-05-01

Head and neck radiotherapy (RT) is a risk factor for cerebrovascular disease. We performed a retrospective cohort study to evaluate carotid artery stenosis (CAS) incidence in head and neck cancer (HNC) patients undergoing RT, characterizing associated risk factors. Records were retrospectively reviewed for HNC patients undergoing carotid ultrasound screening after definitive or adjuvant RT between January 2000 and May 2016. CAS was defined as ≥50% stenosis on imaging, stroke, or transient ischemic attack. Actuarial CAS rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses predicted CAS risk based on carotid dosimetric and clinical parameters. 366 patients met inclusion criteria. Median time from RT completion to last follow-up was 4.1 yr. Actuarial risk for CAS was 29% (95% CI 22-36%) at 8 years. Univariate analysis showed that smoking (HR 1.7; 95% CI 1.1-2.7), hyperlipidemia (HR 1.6; 95% CI 1.03-2.6), diabetes (HR 2.8; 95% CI 1.6-4.8), coronary artery disease (HR 2.4; 95% CI 1.4-4.2), and peripheral artery disease (HR 3.6; 95% CI 1.1-11.6) were significantly associated with increased CAS. In multivariate analysis, diabetes was predictive of time to CAS (HR 1.9; 95% CI 1.1-3.4). Carotid dose parameters were not significantly associated with CAS. CAS incidence is high after head and neck radiotherapy, gradually rising over time. No clear dose-response effect between carotid dose and CAS was identified for HNC patients. Carotid artery screening and preventative strategies should be employed in this high-risk patient population. Copyright © 2018 Elsevier Ltd. All rights reserved.

The preventive effects of lifestyle intervention on the occurrence of diabetes mellitus and acute myocardial infarction in metabolic syndrome.

PubMed

Kim, D; Yoon, S-J; Lim, D-S; Gong, Y-H; Ko, S; Lee, Y-H; Lee, H S; Park, M-S; Kim, K-H; Kim, Y A

2016-10-01

Metabolic syndrome (MS), as a precursor of diabetes mellitus (DM) and cardiovascular disease, is increasing steadily worldwide. We examined the preventive effects of lifestyle intervention on the occurrence of DM and acute myocardial infarction (AMI) in MS. Observational study on disease occurrence after lifestyle intervention. The lifestyle intervention was administered to subjects with MS participating in a metropolitan lifestyle intervention program for 1 year. The same numbers of non-participating age- and sex-matched subjects with MS were randomly extracted from national health examination data. After intervention or examination, new occurrences of hypertension, DM, and AMI were identified through the national health insurance claims data during 1 year. For DM and AMI, multivariate logistic regression analysis for the factors affecting each disease was performed. In the intervention group and the control group (14,918 in each group), the occurrence of hypertension was 555 (6.07%) and 751 (8.33%), the occurrence of DM was 324 (2.55%) and 488 (3.89%), the occurrence of dyslipidemia was 321 (2.59%) and 373 (2.72%), and the occurrence of AMI was 13 (0.09%) and 26 (0.17%), respectively. In multivariate logistic regression analysis, adjusted odds ratios for intervention were 0.752 (95% confidence interval [CI]: 0.644-0.879) and 0.499 (95% CI: 0.251-0.992) for DM and AMI, respectively, indicating that lifestyle intervention has a preventive effect. Lifestyle intervention in MS has preventive effects on the occurrence of DM and AMI, and long-term follow-up is needed to evaluate these preventive effects in more detail. Copyright © 2016. Published by Elsevier Ltd.

Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Abdominal Operations for Inflammatory Bowel Disease.

PubMed

Lightner, Amy L; Raffals, Laura E; Mathis, Kellie L; Cima, Robert R; Tse, Chung Sang; Pemberton, John H; Dozois, Eric J; Loftus, Edward V

2017-02-01

Vedolizumab was recently approved by the Food and Drug Administration for the treatment of moderate to severe ulcerative colitis [UC] and Crohn's disease [CD]. No study to date has examined the rate of postoperative infectious complications among patients who received vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among inflammatory bowel disease [IBD] patients who received vedolizumab within 12 weeks of an abdominal operation as compared to patients who received tumour necrosis factor α [TNFα] inhibitors or no biological therapy. A retrospective chart review between May 1, 2014 and December 31, 2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort comprised patients who received vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNFα inhibitors or no biological therapy. In total, 94 patients received vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications [53%], 35 of which were surgical site infections [SSIs] [36%]. The vedolizumab group experienced significantly higher rates of any postoperative infection [53% vs 33% anti-TNF and 28% non-biologics; p<0.001] and SSI [37% vs 10% and 13%; p<0.001]. On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative SSI [p<0.001]. Thirty-seven per cent of IBD patients who received vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNFα inhibitors or no biological therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Speech prosody impairment predicts cognitive decline in Parkinson's disease.

PubMed

Rektorova, Irena; Mekyska, Jiri; Janousova, Eva; Kostalova, Milena; Eliasova, Ilona; Mrackova, Martina; Berankova, Dagmar; Necasova, Tereza; Smekal, Zdenek; Marecek, Radek

2016-08-01

Impairment of speech prosody is characteristic for Parkinson's disease (PD) and does not respond well to dopaminergic treatment. We assessed whether baseline acoustic parameters, alone or in combination with other predominantly non-dopaminergic symptoms may predict global cognitive decline as measured by the Addenbrooke's cognitive examination (ACE-R) and/or worsening of cognitive status as assessed by a detailed neuropsychological examination. Forty-four consecutive non-depressed PD patients underwent clinical and cognitive testing, and acoustic voice analysis at baseline and at the two-year follow-up. Influence of speech and other clinical parameters on worsening of the ACE-R and of the cognitive status was analyzed using linear and logistic regression. The cognitive status (classified as normal cognition, mild cognitive impairment and dementia) deteriorated in 25% of patients during the follow-up. The multivariate linear regression model consisted of the variation in range of the fundamental voice frequency (F0VR) and the REM Sleep Behavioral Disorder Screening Questionnaire (RBDSQ). These parameters explained 37.2% of the variability of the change in ACE-R. The most significant predictors in the univariate logistic regression were the speech index of rhythmicity (SPIR; p = 0.012), disease duration (p = 0.019), and the RBDSQ (p = 0.032). The multivariate regression analysis revealed that SPIR alone led to 73.2% accuracy in predicting a change in cognitive status. Combining SPIR with RBDSQ improved the prediction accuracy of SPIR alone by 7.3%. Impairment of speech prosody together with symptoms of RBD predicted rapid cognitive decline and worsening of PD cognitive status during a two-year period. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oncologic outcomes in patients with nonurothelial bladder cancer.

PubMed

Patel, Sanjay G; Weiner, Adam Benjamin; Keegan, Kirk; Morgan, Todd

2018-01-01

We aimed to evaluate the relative prognostic impact of the most common variant histologies on disease-specific survival (DSS) in patients undergoing radical cystectomy. The Surveillance, Epidemiology, and End Result database was used to identify patients who underwent radical cystectomy for bladder cancer from 1990 to 2007. Patients with urothelial cell carcinoma (UCC), squamous cell carcinoma (SCC), adenocarcinoma (AC), sarcoma, small cell carcinoma, signet ring carcinoma, and spindle cell carcinoma were included in the study. Multivariable analysis was performed using Cox proportional hazards model to assess independent predictors of disease-specific survival (DSS). Mortality rates were estimated using Kaplan-Meier analyses. A total of 14,130 patients met inclusion criteria with the following histologies: UCC (90.1%), SCC (4.6%), AC, (2.3%), sarcoma (0.8%), small cell carcinoma (0.8%), signet ring carcinoma (0.5%), and spindle cell carcinoma (0.9%). Three-year DSS was most favorable in patients with UCC (63.7%; 95% confidence interval [62.9%-64.8%]) and AC (65.3% [59.3%-70.6%]), whereas 3-year DSS was the least favorable for small cell carcinoma (41.6% [31.3%-51.6%]) and sarcoma (45.4% [35.1%-55.1%]). In the multivariable analysis, independent predictors of DSS were age, marital status, grade, T-stage, N-stage, and variant histology. With respect to UCC, there was an increased risk of disease-specific death associated with all variants except AC. Sarcoma and spindle cell carcinoma were associated with the highest risk of death. With the exception of AC, the most common variant bladder cancer histologies are all independently associated with worse DSS relative to UCC in patients undergoing radical cystectomy.

Comparison of cystatin C and creatinine to determine the incidence of composite adverse outcomes in HIV-infected individuals.

PubMed

Yanagisawa, Naoki; Sasaki, Shugo; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi; Ando, Minoru

2015-02-01

Cystatin C is an overall biomarker of pathophysiologic abnormalities that accompany chronic kidney disease (CKD). The utility of cystatin C is not fully understood in an HIV-infected population. This prospective study investigated 661 HIV-infected individuals for 4 years to determine the incidence of adverse outcomes, including all-cause mortality, cardiovascular disease, and renal dysfunction. The risk of developing the outcomes was discriminated with a 4 color-coded classification in a 3 × 6 contingency table, that combined 3 grades of dipstick proteinuria with 6 grades of estimated glomerular filtration rate (eGFR) calculated using either serum creatinine (eGFRcr) or cystatin C (eGFRcy): green, low risk; yellow, moderately increased risk; orange, high risk; and red, very high risk. The cumulative incidence of the outcomes was assessed by the Kaplan-Meier method, and the association between color-coded risk and the time to outcome was evaluated using multivariate proportional hazards analysis. Compared with eGFRcr, the use of eGFRcy reduced the prevalence of risk ≥ orange by 0.8%. The adverse outcomes were significantly more likely to occur to the patients with baseline risk category ≥orange than those with ≤ yellow, independent of risk categories based on eGFRcr or eGFRcy. However, in multivariate analysis, risk category ≥orange with eGFRcy-based classification was significantly associated with adverse outcomes, but not the one with eGFRcr. Replacing creatinine by cystatin C in the CKD color-coded risk classification may be appropriate to discriminate HIV-infected patients at increased risk of a poor prognosis. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Working after a metastatic cancer diagnosis: factors affecting employment in the metastatic setting from ECOG’s Symptom Outcomes and Practice Patterns (SOAPP) study

PubMed Central

Tevaarwerk, Amye; Lee, Ju-Whei; Terhaar, Abigail; Sesto, Mary; Smith, Mary Lou; Cleeland, Charles; Fisch, Michael

2015-01-01

Background Improved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. Better understanding of how metastatic cancer affects employment is a necessary step towards the development of tools to assist survivors in this important realm. Methods We analyzed the Eastern Cooperative Oncology Group’s “Symptom Outcomes and Practice Patterns (SOAPP)” study to investigate what factors were associated with employment of 680 metastatic cancer patients. Univariable and multivariable logistic regression analyses were conducted to compare patients stably working (Group A) to patients no longer working (Group B). Results There were 668 metastatic working-age participants in our analysis; 236 (35%) worked full or part-time while 302 (45%) stopped working due to illness. Overall, 58% reported some change in employment due to illness. Better performance status and non-Hispanic White ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis on multivariable analysis. Disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. Conclusions A significant percentage of metastatic patients remain employed; symptom burden was associated with change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working, if desired. Improvements in symptom control and strategies developed to help address work place difficulties have promise to improve this aspect of survivorship. PMID:26687819

Ethnicity and association with disease manifestations and mortality in Behçet's disease.

PubMed

Savey, Lea; Resche-Rigon, Mathieu; Wechsler, Bertrand; Comarmond, Cloé; Piette, Jean Charles; Cacoub, Patrice; Saadoun, David

2014-03-27

Behçet's disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis.

Ethnicity and association with disease manifestations and mortality in Behçet’s disease

PubMed Central

2014-01-01

Background Behçet’s disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. Methods We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. Results 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). Conclusion We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis. PMID:24674137

Trajectories of caregiver burden in families of adult cystic fibrosis patients.

PubMed

Wojtaszczyk, Ann; Glajchen, Myra; Portenoy, Russell K; Berdella, Maria; Walker, Patricia; Barrett, Malcolm; Chen, Jack; Plachta, Amy; Balzano, Julie; Fresenius, Ashley; Wilder, Kenya; Langfelder-Schwind, Elinor; Dhingra, Lara

2017-10-17

Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden. This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.

The Occurrence of Diseases and Related Factors in a Center for Asylum Seekers in Italy.

PubMed

Firenze, Alberto; Aleo, Nicola; Ferrara, Clara; Maranto, Marianna; LA Cascia, Caterina; Restivo, Vincenzo

2016-03-01

Italy is the main recipient of asylum seekers in the European region, and Sicily is their first point of arrival. This geographical position creates a large job for Health Authorities to identify and deal with the health of immigrants. This study evaluates the prevalence of disease among asylum seekers, assessing which are associated factors. A cross-sectional study was conducted to analyse demographic and clinical data in an Acceptance Centres for Asylum Seekers from February 2012 to May 2013. All variables that were found to be significant on unvariable analysis for the most frequent pathologies were included in a multivariable logistic regression model. Post-traumatic stress disorders with 17.4% and major depression with 7.3% were the most frequent diseases. The factors associated with post-traumatic stress disorders among asylum seekers were: major depression diagnosis (OR=2.91, p=0.004), Pakistan as a country of origin (OR=3.88, p<0.001), the largest number of medical visits (OR=1.02, p=0.033) and refugee status (OR=1.97, p=0.036). The variables linked with the diagnosis of major depression from the multivariable analysis were: suffering from post-traumatic stress disorders (OR=3.83, p<0.001), Pakistan as a country of origin (OR=3.45, p=0.004) and the highest number of visits to psychologist (OR=1.15, p<0.001). The mental wellbeing of asylum seekers needs special attention, and interventions should be done to prevent the consolidation of psychiatric morbidity. A short psychological screening after the arrival might prove helpful here. Moreover, carefully designed longitudinal studies should be carried out when political recommendations try to change the organization of psychological and healthcare services.

The Occurrence of Diseases and Related Factors in a Center for Asylum Seekers in Italy

PubMed Central

FIRENZE, Alberto; ALEO, Nicola; FERRARA, Clara; MARANTO, Marianna; LA CASCIA, Caterina; RESTIVO, Vincenzo

2016-01-01

Introduction Italy is the main recipient of asylum seekers in the European region, and Sicily is their first point of arrival. This geographical position creates a large job for Health Authorities to identify and deal with the health of immigrants. This study evaluates the prevalence of disease among asylum seekers, assessing which are associated factors. Methods A cross-sectional study was conducted to analyse demographic and clinical data in an Acceptance Centres for Asylum Seekers from February 2012 to May 2013. All variables that were found to be significant on unvariable analysis for the most frequent pathologies were included in a multivariable logistic regression model. Results Post-traumatic stress disorders with 17.4% and major depression with 7.3% were the most frequent diseases. The factors associated with post-traumatic stress disorders among asylum seekers were: major depression diagnosis (OR=2.91, p=0.004), Pakistan as a country of origin (OR=3.88, p<0.001), the largest number of medical visits (OR=1.02, p=0.033) and refugee status (OR=1.97, p=0.036). The variables linked with the diagnosis of major depression from the multivariable analysis were: suffering from post-traumatic stress disorders (OR=3.83, p<0.001), Pakistan as a country of origin (OR=3.45, p=0.004) and the highest number of visits to psychologist (OR=1.15, p<0.001). Conclusions The mental wellbeing of asylum seekers needs special attention, and interventions should be done to prevent the consolidation of psychiatric morbidity. A short psychological screening after the arrival might prove helpful here. Moreover, carefully designed longitudinal studies should be carried out when political recommendations try to change the organization of psychological and healthcare services. PMID:27647085

Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

PubMed

Lian, Zhou-Yang; Li, He-Hong; Zhang, Bin; Dong, Yu-Hao; Deng, Wu-Xu; Liu, Jing; Luo, Xiao-Ning; Huang, Biao; Liang, Chang-Hong; Zhang, Shui-Xing

The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Association of socioeconomic status measured by education and risk factors for carotid atherosclerosis: cross-sectional study.

PubMed

Maksimović, Milos Z; Vlajinac, Hristina D; Radak, Dorde J; Maksimović, Jadranka M; Marinković, Jelena M; Jorga, Jagoda B

2008-12-01

To investigate the association between socioeconomic status and metabolic syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory markers as risk factors for carotid atherosclerotic disease. This cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia, during the period 2006-2007. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education--low (< or = primary school), medium (secondary school), and high (university education). In the analysis, univariate and multivariate logistic regressions were used. Multivariate analysis showed that low education was significantly positively associated with female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81), increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR, 0.42; 95% CI, 0.23-0.75). Medium education was significantly positively associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97; 95% CI, 0.94-0.99). Increased triglycerides and hsCRP in people with low and medium education, and high prevalence of metabolic syndrome, its components and inflammatory markers in all study participants, suggest that regular health check-up, especially for those with lower education, may be useful in early detection and treatment of any abnormality that can be associated with cardiovascular disease.

Prediction of Gestational Diabetes through NMR Metabolomics of Maternal Blood.

PubMed

Pinto, Joana; Almeida, Lara M; Martins, Ana S; Duarte, Daniela; Barros, António S; Galhano, Eulália; Pita, Cristina; Almeida, Maria do Céu; Carreira, Isabel M; Gil, Ana M

2015-06-05

Metabolic biomarkers of pre- and postdiagnosis gestational diabetes mellitus (GDM) were sought, using nuclear magnetic resonance (NMR) metabolomics of maternal plasma and corresponding lipid extracts. Metabolite differences between controls and disease were identified through multivariate analysis of variable selected (1)H NMR spectra. For postdiagnosis GDM, partial least squares regression identified metabolites with higher dependence on normal gestational age evolution. Variable selection of NMR spectra produced good classification models for both pre- and postdiagnostic GDM. Prediagnosis GDM was accompanied by cholesterol increase and minor increases in lipoproteins (plasma), fatty acids, and triglycerides (extracts). Small metabolite changes comprised variations in glucose (up regulated), amino acids, betaine, urea, creatine, and metabolites related to gut microflora. Most changes were enhanced upon GDM diagnosis, in addition to newly observed changes in low-Mw compounds. GDM prediction seems possible exploiting multivariate profile changes rather than a set of univariate changes. Postdiagnosis GDM is successfully classified using a 26-resonance plasma biomarker. Plasma and extracts display comparable classification performance, the former enabling direct and more rapid analysis. Results and putative biochemical hypotheses require further confirmation in larger cohorts of distinct ethnicities.

Síndrome metabólico y otros factores asociados a gonartrosis.

PubMed

Charles-Lozoya, Sergio; Treviño-Báez, Joaquín Darío; Ramos-Rivera, Jesús Alejandro; Rangel-Flores, Jesús María; Tamez-Montes, Juan Carlos; Brizuela-Ventura, Jesús Miguel

2017-01-01

To evaluate whether an association exists between gonarthrosis and metabolic syndrome X (MS) as well as other potential risk factors. Comparative cross-sectional study of 310 patients evaluated by pathology of knee grouped in patients with gonarthrosis and without it. Sociodemographic, anthropometric and laboratory data was obtained. Gonarthrosis was defined as a ≥ 2 score in Kellgren-Lawrence radiological scale, and MS was assessed using the International Diabetes Federation criteria. Odds ratio and logistic regression were used for bivariate and multivariate analysis respectively. The prevalence of MS in patients who had gonarthrosis was 79.9%, statistically higher than in patients without gonarthrosis (p = 0.001). Other factors that had a statistically higher frequency in this group included diabetes mellitus (p = 0.02) and hypertension (p = 0.02). Multivariate analysis revealed MS had an association with a higher prevalence of gonarthrosis (p = 0.003), while high density lipoproteins (p = 0.02) was associated with a lower prevalence. MS and its related alterations are associated to gonarthrosis; their adequate control could prevent patients from developing the disease. Copyright: © 2017 SecretarÍa de Salud

Factors predictive of survival after stapler hepatectomy of hepatocellular carcinoma: a multivariate, single-center analysis.

PubMed

Hoffmann, Katrin; Müller-Bütow, Verena; Franz, Clemens; Hinz, Ulf; Longerich, Thomas; Büchler, Markus W; Schemmer, Peter

2014-02-01

New technical devices for hepatic parenchymal transection have improved perioperative safety and patient survival. The aim of the present study was to determine the oncological outcome after stapler hepatectomy in patients with HCC. Data of 95 patients who underwent stapler hepatectomy for HCC between 2001 and 2011 were analyzed retrospectively regarding clinical safety of the procedure and predictive factors for survial. Thirty-nine minor (≤2 segments) and 56 major (≥3 segments) hepatic resections were performed. The median survival was 47.5 months, after 36 months follow-up. Low grading, tumors ≥5 cm, multiple nodules and liver cirrhosis were predictors of decreased overall survival using multivariate analysis with hazard ratio(HR)=2.62, 2.41, 2.05, and 1.92 respectively. An estimated intra-operative blood loss of ≥1.2l was inversely correlated to disease free survival (HR=1.96). Stapler hepatectomy is a safe procedure in patients with HCC. Substantial intraoperative blood loss and the presence of cirrhosis independently predict the overall probability of patient survival. Intraoperative blood loss directly impacts HCC recurrence.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.

PubMed

Ikeda, Yuki; Ishii, Shunsuke; Fujita, Teppei; Iida, Yuichiro; Kaida, Toyoji; Nabeta, Takeru; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Inomata, Takayuki; Ako, Junya

2017-03-01

Intestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes. Copyright © 2016. Published by Elsevier B.V.

Determinants of survival after liver resection for metastatic colorectal carcinoma.

PubMed

Parau, Angela; Todor, Nicolae; Vlad, Liviu

2015-01-01

Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate analysis. In our series predictors of outcome in multivariate analysis were resection margins beyond 1mm and perioperative chemotherapy. Studies on larger population and analyses of additional clinicopathologic factors like genetic markers could contribute to development of clinical scoring models to assess the risk of relapse and survival.

Lymphopenia Association With Gross Tumor Volume and Lung V5 and Its Effects on Non-Small Cell Lung Cancer Patient Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Chad; Liao, Zhongxing, E-mail: zliao@mdanderson.org; Gomez, Daniel

2014-08-01

Purpose: Radiation therapy (RT) can both suppress and stimulate the immune system. We sought to investigate the mechanisms underlying radiation-induced lymphopenia and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Methods and Materials: Subjects consisted of 711 patients who had received definitive RT for NSCLC. A lymphocyte nadir was calculated as the minimum lymphocyte value measured during definitive RT. Associations between gross tumor volumes (GTVs) and lung dose-volume histogram (DVH) parameters with lymphocyte nadirs were assessed with Spearman correlation coefficients. Relationships between lymphocyte nadirs with overall survival (OS) and event free survival (EFS) were evaluated with Kaplan-Meiermore » analysis and compared with log-rank test results. Multivariate regressions were conducted with linear and Cox regression analyses. All variables were analyzed as continuous if possible. Results: Larger GTVs were correlated with lower lymphocyte nadirs regardless of concurrent chemotherapy receipt (with concurrent: r = −0.26, P<.0001; without: r = −0.48, P<.0001). Analyses of lung DVH parameters revealed significant correlations at lower doses (lung V5-V10: P<.0001) that incrementally decreased and became nonsignificant at higher doses (lung V60-V70: P>.05). Of note, no significant associations were detected between GTV and lung DVH parameters with total leukocyte, neutrophil, or monocyte nadirs during RT or with lymphocyte count prior to RT. Multivariate analysis revealed larger GTV (P<.0001), receipt of concurrent chemotherapy (P<.0001), twice-daily radiation fractionation (P=.02), and stage III disease (P=.05) to be associated with lower lymphocyte nadirs. On univariate analysis, patients with higher lymphocyte nadirs exhibited significantly improved OS (hazard ratio [HR] = 0.51 per 10{sup 3} lymphocytes/μL, P=.01) and EFS (HR = 0.46 per 10{sup 3} lymphocytes/μL, P<.0001). These differences held on multivariate analyses, controlling for common disease and treatment characteristics including GTV. Conclusions: Lower lymphocyte nadirs during definitive RT were associated with larger GTVs and worse patient outcomes.« less

Diversity pattern in Sesamum mutants selected for a semi-arid cropping system.

PubMed

Murty, B R; Oropeza, F

1989-02-01

Due to the complex requirements of moisture stress, substantial genetic diversity with a wide array of character combinations and effective simultaneous selection for several variables is necessary for improving the productivity and adaptation of a component crop in order for it to fit into a cropping system under semi-arid tropical conditions. Sesamum indicum L. is grown in Venezuela after rice/sorghum/or maize under such conditions. A mutation breeding program was undertaken using six locally adapted varieties to develop genotypes suitable for the above system. The diversity pattern for nine variables was assessed by multivariate analysis in 301 M4 progenies. Analysis of the characteristic roots and principal components in three methods of selection, i.e., M2 bulks (A), individual plant selection throughout (B), and selection in M3 for single variable (C), revealed differences in the pattern of variation between varieties, selection methods, and varieties x methods interactions. Method B was superior to the others and gave 17 of the 21 best M5 progenies. 'Piritu' and 'CF' varieties yielded the most productive progenies in M5 and M6. Diversity was large and selection was effective for such developmental traits as earliness and synchrony, combined with multiple disease resistance, which could be related to their importance by multivariate analyses. Considerable differences in the variety of character combinations among the high yielding. M5 progenies of 'CF' and 'Piritu' suggested possible further yield improvement. The superior response of 'Piritu' and 'CF' over other varieties in yield and adaptation was due to major changes in plant type and character associations. Multilocation testing of M5 generations revealed that the mutant progenies had a 40%-100% yield superiority over the parents; this was combined with earliness, synchrony, and multiple disease resistance, and was confirmed in the M6 generation grown on a commercial scale. This study showed that multivariate analysis is an effective tool for assessing diversity patterns, choice of appropriate variety, and selection methodology in order to make rapid progress in meeting the complex requirements of semi-arid cropping systems.

Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

2014-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

PubMed

Federici, Silvia; Sormani, Maria Pia; Ozen, Seza; Lachmann, Helen J; Amaryan, Gayane; Woo, Patricia; Koné-Paut, Isabelle; Dewarrat, Natacha; Cantarini, Luca; Insalaco, Antonella; Uziel, Yosef; Rigante, Donato; Quartier, Pierre; Demirkaya, Erkan; Herlin, Troels; Meini, Antonella; Fabio, Giovanna; Kallinich, Tilmann; Martino, Silvana; Butbul, Aviel Yonatan; Olivieri, Alma; Kuemmerle-Deschner, Jasmin; Neven, Benedicte; Simon, Anna; Ozdogan, Huri; Touitou, Isabelle; Frenkel, Joost; Hofer, Michael; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco

2015-05-01

The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

PubMed

Ardoin, S P; Schanberg, L E; Sandborg, C; Yow, E; Barnhart, H X; Mieszkalski, K l; Ilowite, N T; von Scheven, E; Eberhard, A; Levy, D M; Kimura, Y; Silverman, E; Bowyer, S L; Punaro, L; Singer, N G; Sherry, D D; McCurdy, D; Klein-Gitelman, M; Wallace, C; Silver, R; Wagner-Weiner, L; Higgins, G C; Brunner, H I; Jung, L K; Imundo, L; Soep, J B; Reed, A M

2010-10-01

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Incidence and Risk Factors for Perioperative Cardiovascular and Respiratory Adverse Events in Pediatric Patients With Congenital Heart Disease Undergoing Noncardiac Procedures.

PubMed

Lee, Sandra; Reddington, Elise; Koutsogiannaki, Sophia; Hernandez, Michael R; Odegard, Kirsten C; DiNardo, James A; Yuki, Koichi

2018-04-27

While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal, general surgery, and maxillofacial procedures. Intraoperative cardiovascular events and respiratory events in patients with CHD were relatively common. While cardiovascular events were highly associated with cardiovascular status, respiratory events were not associated with cardiovascular status.

Metastasis in dedifferentiated liposarcoma: Predictors and outcome in 148 patients.

PubMed

Tirumani, S H; Tirumani, H; Jagannathan, J P; Shinagare, A B; Hornick, J L; Ramaiya, N H; Wagner, A J

2015-07-01

To describe the pattern of dedifferentiated liposarcoma (DDLPS) metastases and to analyze their predictors and outcome. In this retrospective study, we reviewed the imaging and clinical records of all consenting patients with histopathology-confirmed DDLPS seen from 2000 through 2012. The predictive value of clinical and histopathologic parameters for metastasis later in the disease course was analyzed using univariate and multivariate analyses. Survival of patients with and without metastasis was compared using Log-rank test. Records of 148 patients (57 women, 91 men; mean age 59 years, range 30-87 years) were reviewed. Distant metastases were observed in 44/148 patients (29.7%), 9/44 (20.5%) at presentation and 35/44 (79.5%) developing them later at a median interval of 8 months (IQR = 0.80-26 months). Median duration of follow-up was 38 months (IQR = 18-74 months) with 77/148 patients (31 with metastases) deceased at the time of analysis. Median survival was 28 months (IQR = 10-56 months) for patients with metastases and 38 months (IQR, 17-65 months) for patients without metastases (p = 0.0123, Log-Rank test; Hazard ratio 1.79 [95% confidence interval 1.11-2.84]). Lung was the most common site of metastases (33 patients, 22.3%). On univariate analysis, grade and local recurrence were associated with subsequent risk of metastasis where as age, tumor size, site, de novo dedifferentiation, number of previous surgical resections, margin positivity and chemoradiation were not. On multivariate analysis, high tumor grade (p-value = 0.0005, OR 5.05; 95% CI 2.01-13.48) and local recurrence (p-value = 0.0025, OR 4.46; 95% CI 1.67-13.40) predicted metastasis. Lung was most frequent site of DDLPS metastases. Risk of developing metastatic disease was statistically associated with tumor grade and local recurrence. Metastatic disease was associated with decreased survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increasing time to treatment initiation for head and neck cancer: an analysis of the National Cancer Database.

PubMed

Murphy, Colin T; Galloway, Thomas J; Handorf, Elizabeth A; Wang, Lora; Mehra, Ranee; Flieder, Douglas B; Ridge, John A

2015-04-15

The objective of this study was to identify trends and predictors of the time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). The National Cancer Database (NCDB) was reviewed for the following head and neck cancer sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was defined as the number of days from diagnosis to the initiation of definitive treatment and was measured according to covariates. Significant differences in the median TTI across each covariate were measured using the Kruskal-Wallis test, and the Spearman test was used to measure trends within covariates. For multivariate analysis, a zero-inflated, negative, binomial regression model was used to estimate the expected TTI, which was expressed in the predicted number of days; and the Vuong test was used to identify the predictors of TTI. In total, 274,630 patients were included. Between 1998 and 2011, the median TTI for all patients was 26 days, and it increased from 19 days to 30 days (P < .0001). Treatment with chemoradiation (CRT) (P < .0001), treatment at academic facilities (P < .0001), and stage IV disease (P < .0001) were associated with increased TTI. TTI significantly increased for each disease stage (P < .0001), treatment modality (P < .0001), and facility type (P < .0001) over time. In addition, patients became more likely to transition care between facilities after diagnosis for treatment initiation (P < .0001) over time. On multivariate analysis, treatment at academic facilities (33 days), transitioning care (37 days), and receipt of CRT (39 days) predicted for a longer TTI. TTI is rising for patients with HNSCC. Those who have advanced-stage disease, receive treatment with CRT, are treated at academic facilities, and who have a transition in care realized the greatest increases in TTI. © 2014 American Cancer Society.

Selective intestinal decontamination with fluoroquinolones for the prevention of early bacterial infections after liver transplantation.

PubMed

San-Juan, Rafael; Aguado, Jose M; Lumbreras, Carlos; Fortun, Jesus; Len, Oscar; Munoz, Patricia; Montejo, Miguel; Moreno, Asunción; Cordero, Elisa; Blanes, Marino; Ramos, Antonio; Torre-Cisneros, Julian; López-Medrano, Francisco; Carratala, Jordi; Moreno, Enrique

2011-08-01

The role of selective intestinal decontamination with fluoroquinolones (FQ-SID) in the prevention of early bacterial infections (EBIs) in liver transplant recipients (LTRs) is unknown. We used the online database of the Spanish Network of Infection in Transplantation/Spanish Network for Research in Infectious Diseases, which prospectively analyzed 1010 LTRs from 12 Spanish hospitals from September 2003 to February 2005. We compared the incidence and etiology of EBIs (30 days after transplantation) in 415 LTRs from 4 centers that used FQ-SID (>7 days) and in 595 LTRs from 8 hospitals that did not use FQ-SID. A multivariate logistic regression analysis (including an adjustment for the transplant center factor) was performed to evaluate the potential protective factor of FQ-SID in the development of EBIs. We reported 266 EBI episodes in 252 LTRs (incidence = 24.9%). There were no differences in the incidence of EBIs between patients in the FQ-SID group and patients not in the FQ-SID group [109/415 (26.3%) versus 143/595 (24%), P = 0.9]. Although LTRs who received FQ-SID had a lower incidence of infections due to enteric bacteria (2.7% versus 6.5%, P = 0.007) and a higher incidence of infections due to nonfermenting gram-negative bacilli (6.6% versus 2.6%, P = 0.004), these findings could not be confirmed after an adjustment by the center factor in the multivariate models. We found no significant differences in the incidence of enterococcal infections (3.4% with FQ-SID versus 3.9% without FQ-SID, P = 0.5). Multivariate analysis did not confirm any protective effect of FQ-SID against the development of EBIs by enteric bacteria. In conclusion, FQ-SID does not reduce the incidence of EBIs in LTRs and could be withheld from this group of patients. Copyright © 2011 American Association for the Study of Liver Diseases.

Dose-surface analysis for prediction of severe acute radio-induced skin toxicity in breast cancer patients.

PubMed

Pastore, Francesco; Conson, Manuel; D'Avino, Vittoria; Palma, Giuseppe; Liuzzi, Raffaele; Solla, Raffaele; Farella, Antonio; Salvatore, Marco; Cella, Laura; Pacelli, Roberto

2016-01-01

Severe acute radiation-induced skin toxicity (RIST) after breast irradiation is a side effect impacting the quality of life in breast cancer (BC) patients. The aim of the present study was to develop normal tissue complication probability (NTCP) models of severe acute RIST in BC patients. We evaluated 140 consecutive BC patients undergoing conventional three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery in a prospective study assessing acute RIST. The acute RIST was classified according to the RTOG scoring system. Dose-surface histograms (DSHs) of the body structure in the breast region were extracted as representative of skin irradiation. Patient, disease, and treatment-related characteristics were analyzed along with DSHs. NTCP modeling by Lyman-Kutcher-Burman (LKB) and by multivariate logistic regression using bootstrap resampling techniques was performed. Models were evaluated by Spearman's Rs coefficient and ROC area. By the end of radiotherapy, 139 (99%) patients developed any degree of acute RIST. G3 RIST was found in 11 of 140 (8%) patients. Mild-moderate (G1-G2) RIST was still present at 40 days after treatment in six (4%) patients. Using DSHs for LKB modeling of acute RIST severity (RTOG G3 vs. G0-2), parameter estimates were TD50=39 Gy, n=0.38 and m=0.14 [Rs = 0.25, area under the curve (AUC) = 0.77, p = 0.003]. On multivariate analysis, the most predictive model of acute RIST severity was a two-variable model including the skin receiving ≥30 Gy (S30) and psoriasis [Rs = 0.32, AUC = 0.84, p < 0.001]. Using body DSH as representative of skin dose, the LKB n parameter was consistent with a surface effect for the skin. A good prediction performance was obtained using a data-driven multivariate model including S30 and a pre-existing skin disease (psoriasis) as a clinical factor.

Use of Neuroanatomical Pattern Classification to Identify Subjects in At-Risk Mental States of Psychosis and Predict Disease Transition

PubMed Central

Koutsouleris, Nikolaos; Meisenzahl, Eva M.; Davatzikos, Christos; Bottlender, Ronald; Frodl, Thomas; Scheuerecker, Johanna; Schmitt, Gisela; Zetzsche, Thomas; Decker, Petra; Reiser, Maximilian; Möller, Hans-Jürgen; Gaser, Christian

2014-01-01

Context Identification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance imaging–based diagnostic classification of neuropsychiatric patient populations. Objective To determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level. Design Multivariate neuroanatomical pattern classification was performed on the structural magnetic resonance imaging data of individuals in early or late ARMS vs healthy controls (HCs). The predictive power of the method was then evaluated by categorizing the baseline imaging data of individuals with transition to psychosis vs those without transition vs HCs after 4 years of clinical follow-up. Classification generalizability was estimated by cross-validation and by categorizing an independent cohort of 45 new HCs. Setting Departments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. Participants The first classification analysis included 20 early and 25 late at-risk individuals and 25 matched HCs. The second analysis consisted of 15 individuals with transition, 18 without transition, and 17 matched HCs. Main Outcome Measures Specificity, sensitivity, and accuracy of classification. Results The 3-group, cross-validated classification accuracies of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in the second analysis were 90% (HCs vs the rest), 88% (individuals with transition vs the rest), and 86% (individuals without transition vs the rest). Independent HCs were correctly classified in 96% (first analysis) and 93% (second analysis) of cases. Conclusions Different ARMSs and their clinical outcomes may be reliably identified on an individual basis by assessing patterns of whole-brain neuroanatomical abnormalities. These patterns may serve as valuable biomarkers for the clinician to guide early detection in the prodromal phase of psychosis. PMID:19581561

Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

PubMed

Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

2014-01-01

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC. © 2014 International Society for Diseases of the Esophagus.

Contribution of artificial intelligence to the knowledge of prognostic factors in Hodgkin's lymphoma.

PubMed

Buciński, Adam; Marszałł, Michał Piotr; Krysiński, Jerzy; Lemieszek, Andrzej; Załuski, Jerzy

2010-07-01

Hodgkin's lymphoma is one of the most curable malignancies and most patients achieve a lasting complete remission. In this study, artificial neural network (ANN) analysis was shown to provide significant factors with regard to 5-year recurrence after lymphoma treatment. Data from 114 patients treated for Hodgkin's disease were available for evaluation and comparison. A total of 31 variables were subjected to ANN analysis. The ANN approach as an advanced multivariate data processing method was shown to provide objective prognostic data. Some of these prognostic factors are consistent or even identical to the factors evaluated earlier by other statistical methods.

Discriminative analysis of early Alzheimer's disease based on two intrinsically anti-correlated networks with resting-state fMRI.

PubMed

Wang, Kun; Jiang, Tianzi; Liang, Meng; Wang, Liang; Tian, Lixia; Zhang, Xinqing; Li, Kuncheng; Liu, Zhening

2006-01-01

In this work, we proposed a discriminative model of Alzheimer's disease (AD) on the basis of multivariate pattern classification and functional magnetic resonance imaging (fMRI). This model used the correlation/anti-correlation coefficients of two intrinsically anti-correlated networks in resting brains, which have been suggested by two recent studies, as the feature of classification. Pseudo-Fisher Linear Discriminative Analysis (pFLDA) was then performed on the feature space and a linear classifier was generated. Using leave-one-out (LOO) cross validation, our results showed a correct classification rate of 83%. We also compared the proposed model with another one based on the whole brain functional connectivity. Our proposed model outperformed the other one significantly, and this implied that the two intrinsically anti-correlated networks may be a more susceptible part of the whole brain network in the early stage of AD.

Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel

PubMed Central

Harshman, Lauren C.; Chen, Yu-Hui; Liu, Glenn; Carducci, Michael A.; Jarrard, David; Dreicer, Robert; Hahn, Noah; Garcia, Jorge A.; Hussain, Maha; Shevrin, Daniel; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R.; Cooney, Matthew; Vogelzang, Nicholas J.; Picus, Joel; Dipaola, Robert

2018-01-01

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database (ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival. PMID:29261442

Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

PubMed

Nagahara, Yasuomi; Motoyama, Sadako; Sarai, Masayoshi; Ito, Hajime; Kawai, Hideki; Takakuwa, Yoko; Miyagi, Meiko; Shibata, Daisuke; Takahashi, Hiroshi; Naruse, Hiroyuki; Ishii, Junichi; Ozaki, Yukio

2016-07-01

Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA and CCTA might be useful for risk stratification of CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inverse association between age at the time of radiation exposure and extent of disease in cases of radiation-induced childhood thyroid carcinoma in Belarus.

PubMed

Farahati, J; Demidchik, E P; Biko, J; Reiners, C

2000-03-15

Increased incidence of childhood thyroid carcinoma, particularly in the youngest children, has been reported from Belarus since the nuclear reactor accident at Chernobyl in 1986. The relation between disease severity and age at the time of the accident, not previously established in this cohort, was analyzed in this study. The authors studied the association between disease severity, expressed by TNM classification, and age at radiation exposure in a cohort of 483 patients younger than 8 years at the time of the Chernobyl accident who have been diagnosed with differentiated thyroid carcinoma since 1986 at the Center for Thyroid Cancer in Minsk. The associations between age at radiation exposure and TNM categories were compared among 4 groups of patients who were ages <2, 2.1-4, 4.1-6, and 6.1-8 years at the time of the accident. Multivariate discriminant analysis was performed to examine the effects of age at the time of the accident, gender, histology, tumor stage, and N classification on the frequency of distant metastasis. Younger age at the time of the Chernobyl accident was associated with greater extrathyroidal tumor extension (P<0.01) and more lymph node involvement (P<0.0001) and tended to be associated with more distant metastases (P = 0.09). Compared with patients who were ages 6.1-8 years at the time of the accident, patients who were younger than 2 years had significantly more extrathyroidal tumor invasion (P = 0.004), lymph node involvement (P = 0.004), and distant metastases (P = 0.05). The age at diagnosis increased with older age at the time of radiation exposure (linear regression analysis; correlation coefficient = 0. 67; P<0.001). Multivariate analysis revealed that younger age at the time of the accident (P = 0.001) and advanced locoregional tumor extension (P<0.001) were the only powerful factors influencing the risk for distant metastasis of this malignancy. The severity of disease was associated inversely with age at the time of radiation exposure in these cases of radiation-induced childhood thyroid carcinoma. Copyright 2000 American Cancer Society.

Motivations for genetic testing for lung cancer risk among young smokers.

PubMed

O'Neill, Suzanne C; Lipkus, Isaac M; Sanderson, Saskia C; Shepperd, James; Docherty, Sharron; McBride, Colleen M

2013-11-01

To examine why young people might want to undergo genetic susceptibility testing for lung cancer despite knowing that tested gene variants are associated with small increases in disease risk. The authors used a mixed-method approach to evaluate motives for and against genetic testing and the association between these motivations and testing intentions in 128 college students who smoke. Exploratory factor analysis yielded four reliable factors: Test Scepticism, Test Optimism, Knowledge Enhancement and Smoking Optimism. Test Optimism and Knowledge Enhancement correlated positively with intentions to test in bivariate and multivariate analyses (ps<0.001). Test Scepticism correlated negatively with testing intentions in multivariate analyses (p<0.05). Open-ended questions assessing testing motivations generally replicated themes of the quantitative survey. In addition to learning about health risks, young people may be motivated to seek genetic testing for reasons, such as gaining knowledge about new genetic technologies more broadly.

Multivariate longitudinal data analysis with mixed effects hidden Markov models.

PubMed

Raffa, Jesse D; Dubin, Joel A

2015-09-01

Multiple longitudinal responses are often collected as a means to capture relevant features of the true outcome of interest, which is often hidden and not directly measurable. We outline an approach which models these multivariate longitudinal responses as generated from a hidden disease process. We propose a class of models which uses a hidden Markov model with separate but correlated random effects between multiple longitudinal responses. This approach was motivated by a smoking cessation clinical trial, where a bivariate longitudinal response involving both a continuous and a binomial response was collected for each participant to monitor smoking behavior. A Bayesian method using Markov chain Monte Carlo is used. Comparison of separate univariate response models to the bivariate response models was undertaken. Our methods are demonstrated on the smoking cessation clinical trial dataset, and properties of our approach are examined through extensive simulation studies. © 2015, The International Biometric Society.

Analysis techniques for multivariate root loci. [a tool in linear control systems

NASA Technical Reports Server (NTRS)

Thompson, P. M.; Stein, G.; Laub, A. J.

1980-01-01

Analysis and techniques are developed for the multivariable root locus and the multivariable optimal root locus. The generalized eigenvalue problem is used to compute angles and sensitivities for both types of loci, and an algorithm is presented that determines the asymptotic properties of the optimal root locus.

Methods for presentation and display of multivariate data

NASA Technical Reports Server (NTRS)

Myers, R. H.

1981-01-01

Methods for the presentation and display of multivariate data are discussed with emphasis placed on the multivariate analysis of variance problems and the Hotelling T(2) solution in the two-sample case. The methods utilize the concepts of stepwise discrimination analysis and the computation of partial correlation coefficients.

A Primer on Multivariate Analysis of Variance (MANOVA) for Behavioral Scientists

ERIC Educational Resources Information Center

Warne, Russell T.

2014-01-01

Reviews of statistical procedures (e.g., Bangert & Baumberger, 2005; Kieffer, Reese, & Thompson, 2001; Warne, Lazo, Ramos, & Ritter, 2012) show that one of the most common multivariate statistical methods in psychological research is multivariate analysis of variance (MANOVA). However, MANOVA and its associated procedures are often not…

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less

Treatment results of nasopharyngeal carcinoma: a 15-year single institutional experience.

PubMed

Khademi, Bijan; Mahmoodi, Jalal; Omidvari, Shapour; Mohammadianpanah, Mohammad

2006-06-01

Nasopharyngeal Carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs most commonly in people in the South Eastern Asia but its condition in Iran is not much clear. In this retrospective study, we evaluated the treatment characteristics determining the outcome in patients with NPC. In this retrospective study, we reviewed the records of one hundred and seven patients with biopsy proven diagnosis of NPC who were referred to the radiation oncology department, Nemazee Hospital, Shiraz University of Medical Sciences, Iran, during the time period from January 1985 to December 2000. Eightyfive patients (79.4%) received 60-70Gy radiation (1.8- 2Gy/fraction, one fraction per day, and 5 fractions per week). Sixty-two patients (57.5%) received radiotherapy combined with adjuvant chemotherapy which consisted of cisplatin and 5-fluorouracil. Eighty-six patients (80.4%) had WHO II-III histopathologic diagnosis. According to the AJCC 1997 staging system, 4 (3.6%), 3 (2.7%), 33 (30.8%) and 67 (62%) patients were in stages I, II, III and IV, respectively. With a median follow-up of 12 months, the 2-year overall and disease-free survival rates were 35% and 21%, respectively. According to the multivariate analysis for overall survival, patients under 40 years had a better prognosis (p=0.041). Node stage and stage of disease were significant prognostic factors (p=0.0001). On multivariate analysis for disease-free survival, age and node stage were significant prognostic factors. The patients who received more than 60Gy radiation had a better prognosis (p=0.02), however; sequential adjuvant chemotherapy had no impact on survival and response (p=0.6). Our experience confirmed earlier reports showing poor outcomes for locoregionally advanced nasopharyngeal carcinomas. This study failed to demonstrate improvement in the outcome regarding overall and disease-free survival by adding sequential adjuvant chemotherapy after radiotherapy for patients with advanced NPC.

Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

PubMed

Bokma, Jouke P; Zegstroo, Ineke; Kuijpers, Joey M; Konings, Thelma C; van Kimmenade, Roland R J; van Melle, Joost P; Kiès, Philippine; Mulder, Barbara J M; Bouma, Berto J

2018-04-01

To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.

PubMed

Guerra, Glen R; Kong, Joseph C; Bernardi, Maria-Pia; Ramsay, Robert G; Phillips, Wayne A; Warrier, Satish K; Lynch, A Craig; Ngan, Samuel Y; Heriot, Alexander G

2018-02-01

Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. This was a retrospective cohort study. This study was conducted at a quaternary referral center. Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4-150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and poor outcome. See Video Abstract at http://links.lww.com/DCR/A515.

Cigarette smoking and male sex are independent and age concomitant risk factors for the development of ocular sarcoidosis in a new orleans sarcoidosis population

PubMed Central

Janot, Adam C.; Huscher, Dörte; Walker, McCall; Grewal, Harmanjot K.; Yu, Mary; Lammi, Matthew R.; Saketkoo, Lesley Ann

2016-01-01

Introduction Sarcoidosis is a multi-organ system granulomatous disease of unknown origin with an incidence of 1–40/100,000. Though pulmonary manifestations are predominant, ocular sarcoidosis (OS) affects 25–50% of patients with sarcoidosis and can lead to blindness. Methods A retrospective, single-center chart review of sarcoidosis cases investigated variables associated with the development of OS. Inclusion criteria were biopsy-proven sarcoidosis, disease duration greater than 1 year, documented smoking status on chart review and documentation of sarcoid-related eye disease. Multivariate analysis identified independent risk factors for OS. Results Of 269 charts reviewed, 109 patients met inclusion criteria. The OS group had a significantly higher proportion of smokers (71.4%) than without OS (42.0%, p=0.027) with no difference (p=0.61) in median number of pack years. Male sex was significantly higher in the OS group (57.1% versus 26.1%, p=0.009). Median duration of sarcoidosis was higher in the OS group (10 versus 4 years, p=0.031). Multivariate regression identified tobacco exposure (OR=5.25, p=0.007, 95% CI 1.58–17.41), male sex (OR=7.48, p=0.002, 95% CI 2.15–26.01), and age (OR=1.114, p=0.002, 95% CI 1.04–1.19) as concomitant risk factors for the development of OS. Conclusion To date, there are few dedicated investigations of risk factors for OS, especially smoking. This investigation identified male sex, age, and tobacco exposure as independent risk factors for OS. Though disease duration did not withstand regression analysis in this moderately sized group, age at chart review suggests screening for OS should not remit but rather intensify in aging patients with sarcoidosis. PMID:26278693

Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer

PubMed Central

Chu, Michael P.; Hecht, J. Randolph; Slamon, Dennis; Wainberg, Zev A.; Bang, Yung-Jue; Hoff, Paulo M.; Sobrero, Alberto; Qin, Shukui; Afenjar, Karen; Houe, Vincent; King, Karen; Koski, Sheryl; Mulder, Karen; Hiller, Julie Price; Scarfe, Andrew; Spratlin, Jennifer; Huang, Yingjie J.; Khan-Wasti, Saba; Chua, Neil

2016-01-01

Importance Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib. Proton pump inhibitor use was identified by medication records. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with PPIs vs patients who were not. Specific subgroups were accounted for, such as younger age (<60 years), Asian ethnicity, female sex, and disease stage (metastatic/advanced) in multivariate Cox proportional hazards modeling. The TRIO-013 trial accrued and randomized patients between June 2008 and January 2012; this analysis took place in January 2014. Interventions Patients were divided based on PPI exposure. Main Outcomes and Measures Primary study outcome was PFS and OS between patients treated with PPIs vs patients who were not. Secondary outcomes included disease response rates and toxicities. Results Of the 545 patients with GEC (median age, 60 years; 406 men [74%]) included in the study, 229 received PPIs (42.0%) and were evenly distributed between arms. In the placebo arm, PPI-treated patients had poorer median PFS, 4.2 vs 5.7 months (hazard ratio [HR], 1.55; 95% CI, 1.29-1.81, P < .001); OS, 9.2 vs 11.3 months (HR, 1.34; 95% CI, 1.06-1.62; P = .04); and disease control rate (72% vs 83%; P = .02) vs patients not treated with PPIs. In multivariate analysis considering age, race, disease stage, and sex, PPI-treated patients had poorer PFS (HR, 1.68; 95% CI, 1.42-1.94; P < .001) and OS (HR, 1.41; 95% CI, 1.11-1.71; P = .001). In patients treated with CapeOx and lapatinib, PPIs had less effect on PFS (HR, 1.08; P = .54) and OS (HR, 1.26; P = .10); however, multivariate analysis in this group demonstrated a significant difference in OS (HR, 1.38; 95% CI, 1.06-1.66; P = .03). Conclusions and Relevance Proton pump inhibitors negatively effected capecitabine efficacy by possibly raising gastric pH levels, leading to altered dissolution and absorption. These results are consistent with previous erlotinib and sunitinib studies. Whether PPIs affected lapatinib is unclear given concurrent capecitabine. Given capecitabine’s prevalence in treatment breast cancer and colon cancer, further studies are under way. Trial Registration clinicaltrials.gov Identifier: NCT00680901 PMID:27737436

Smoking does influence disease behaviour and impacts the need for therapy in Crohn's disease in the biologic era.

PubMed

Nunes, T; Etchevers, M J; Domènech, E; García-Sánchez, V; Ber, Y; Peñalva, M; Merino, O; Nos, P; Garcia-Planella, E; Casbas, A G; Esteve, M; Taxonera Samsó, C; Montoro Huguet, M; Gisbert, J P; Martín Arranz, M D; García-Sepulcre, M F; Barreiro-de Acosta, M; Beltrán, B; Alcaide Suárez, N; Saro Gismera, C; Cabriada, J L; Cañas-Ventura, A; Gomollón, F; Panés, J

2013-10-01

Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers. © 2013 John Wiley & Sons Ltd.

Prognostic factors and treatment outcomes in 444 patients with mucosal melanoma.

PubMed

Heppt, Markus V; Roesch, Alexander; Weide, Benjamin; Gutzmer, Ralf; Meier, Friedegund; Loquai, Carmen; Kähler, Katharina C; Gesierich, Anja; Meissner, Markus; von Bubnoff, Dagmar; Göppner, Daniela; Schlaak, Max; Pföhler, Claudia; Utikal, Jochen; Heinzerling, Lucie; Cosgarea, Ioana; Engel, Jutta; Eckel, Renate; Martens, Alexander; Mirlach, Laura; Satzger, Imke; Schubert-Fritschle, Gabriele; Tietze, Julia K; Berking, Carola

2017-08-01

Mucosal melanoma (MM) is a rare but diverse cancer entity. Prognostic factors are not well established for Caucasians with MM. We analysed the disease course of 444 patients from 15 German skin cancer centres. Disease progression was determined with the cumulative incidence function. Survival times were estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariate Cox regression analysis. Common anatomic sites of primary tumours were head and neck (MMHN, 37.2%), female genital tract (MMFG, 30.4%) and anorectal region (MMAN, 21.8%). MMAN patients showed the highest vertical tumour thickness (p = 0.001), had a more advanced nodal status (p = 0.014) and a higher percentage of metastatic disease (p = 0.001) at diagnosis. Mutations of NRAS (13.8%), KIT (8.6%) and BRAF (6.4%) were evenly distributed across all tumour site groups. Local relapses were observed in 32.4% and most commonly occurred in the MMHN group (p = 0.016). Male gender (p = 0.047), advanced tumour stage (p = 0.001), nodal disease (p = 0.001) and incomplete resection status (p = 0.001) were independent risk factors for disease progression. Overall survival (OS) was highest in the MMFG group (p = 0.030) and in patients without ulceration (p = 0.004). Multivariate risk factors for OS were M stage at diagnosis (p = 0.002) and incomplete resection of the primary tumour (p = 0.001). In this large series of MM patients in a European population, anorectal MM was associated with the poorest prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk factors for peristomal pyoderma gangrenosum complicating inflammatory bowel disease.

PubMed

Wu, Xian-rui; Mukewar, Saurabh; Kiran, Ravi P; Remzi, Feza H; Hammel, Jeffery; Shen, Bo

2013-06-01

Risk factors for peristomal pyoderma gangrenosum (PPG) are not well defined. The aim of this study was to evaluate risk factors associated with development of PPG. Both PPG patients and controls were obtained by searching a database of the Cleveland Clinic using the ICD-9 code from March 2005 to May 2011. The control group was selected by matching for underlying diseases and type of stoma in a ratio of 3:1. Univariate and multivariate analyses were performed. A total of 15 PPG cases and 45 controls were included. The mean age at the time of PPG diagnosis was 46.0 ± 14.4 years. The underlying disease was Crohn's disease in 7 patients (46.7%), ulcerative colitis in 7 (46.7%) and indeterminate colitis in 1 (6.7%). Eleven patients (73.3%) had end ileostomy, 3 (20.0%) had loop ileostomy and 1 (6.7%) had colostomy. Eleven patients (73.3%) had active intestinal disease. In multivariate analysis, female gender, the presence of concurrent autoimmune disorders, and a high body mass index (BMI) were significantly associated with the presence of PPG, with odds ratios of 8.385 (95% confidence interval [CI]: 1.496-46.982, p=0.015), 6.882 (95% CI:1.438-32.941, p=0.016), and 9.895 (95% CI: 1.970-43.704, p=0.005), respectively. After a median follow-up of 12.8 (interquartile range: 7.9-20.1) months with appropriate therapy, PPG healed in 8 patients (53.3%) and improved in 7 (46.7%) patients, after treatment. Female gender, the presence of autoimmune disorders and a high BMI appeared to be associated with an increased risk for the development of PPG in IBD patients. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Elevated serum creatinine and low albumin are associated with poor outcomes in patients with liposarcoma.

PubMed

Panotopoulos, Joannis; Posch, Florian; Funovics, Philipp T; Willegger, Madeleine; Scharrer, Anke; Lamm, Wolfgang; Brodowicz, Thomas; Windhager, Reinhard; Ay, Cihan

2016-03-01

Low serum albumin levels and impaired kidney function have been associated with decreased survival in patients with a variety of cancer types. In a retrospective cohort study, we analyzed 84 patients with liposarcoma treated at from May 1994 to October 2011. Uni- and multivariable Cox proportional hazard models and competing risk analyses were performed to evaluate the association between putative biomarkers with disease-specific and overall survival. The median age of the study population was 51.7 (range 19.6-83.8) years. In multivariable analysis adjusted for AJCC tumor stage, serum creatinine was highly associated with disease-specific survival (Subdistribution Hazard ratio (SHR) per 1 mg/dl increase = 2.94; 95%CI 1.39-6.23; p = 0.005). High albumin was associated with improved overall and disease-specific survival (Hazard Ratio (HR) per 10 units increase = 0.50; 95%CI 0.26-0.95; p = 0.033 and SHR = 0.64; 95%CI 0.42-1.00; p = 0.049). The serum albumin-creatinine-ratio emerged to be associated with both overall and disease-specific survival after adjusting for AJCC tumor stage (HR = 0.95; 95%CI 0.92-0.99; p = 0.011 and SHR = 0.96; 95%CI 0.93-0.99; p = 0.08). Our study provides evidence for a tumor-stage-independent association between higher creatinine and lower albumin with worse disease-specific survival. Low albumin and a high albumin-creatinine-ratio independently predict poor overall survival. Our work identified novel prognostic biomarkers for prognosis of patients with liposarcoma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease.

PubMed

Paulin, Laura M; Diette, Gregory B; Blanc, Paul D; Putcha, Nirupama; Eisner, Mark D; Kanner, Richard E; Belli, Andrew J; Christenson, Stephanie; Tashkin, Donald P; Han, MeiLan; Barr, R Graham; Hansel, Nadia N

2015-03-01

Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. To determine the impact of occupational exposures on COPD morbidity. A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

Racial Disparities Differ for African Americans and Hispanics in the Diagnosis and Treatment of Penile Cancer.

PubMed

Slopnick, Emily A; Kim, Simon P; Kiechle, Jonathan E; Gonzalez, Christopher M; Zhu, Hui; Abouassaly, Robert

2016-10-01

To evaluate racial disparities in the diagnosis and treatment of penile cancer among a contemporary series of men from a large diverse national data base. Using the 1998-2012 National Cancer Data Base, all men with squamous cell carcinoma (SCC) were stratified by race and ethnicity. Demographic and disease characteristics were compared between groups. Likelihood of undergoing surgery and type of surgery were compared among patients with nonmetastatic disease. Factors influencing disease stage and treatment type were analyzed with univariate and multivariable logistic regressions. Overall survival was examined with Kaplan-Meier and adjusted Cox proportional hazard models. We identified 12,090 men with penile SCC with median age 66 years (range 18-90). Distribution of patients is as follows: 76.8% Caucasian, 10.2% African American (AA), 8.7% Hispanic. On multivariable analysis, Hispanic men are more likely to present with high-risk (≥T1G3) penile SCC (odds ratio [OR] 1.6; confidence interval [CI] 1.20-2.00; P = .001) and tend to undergo penectomy rather than penile-sparing surgery (OR 1.46; CI 1.15-1.85; P = .002) for equal stage SCC compared to Caucasian patients. Whereas AA men are less likely to undergo surgery of any type (OR 0.67; CI 0.51-0.87; P = .003) and have higher mortality rates than Caucasian patients (hazard ratio 1.25; CI 1.10-1.42; P < .001). Hispanic men with penile SCC are more likely to present with high-risk disease and undergo more aggressive treatment than Caucasian patients but have comparable survival. AA men are less likely to undergo surgical management of their disease and have higher mortality rates. Copyright © 2016 Elsevier Inc. All rights reserved.

Excessive weight gain is associated with an increased risk for pouch failure in patients with restorative proctocolectomy.

PubMed

Wu, Xian-Rui; Zhu, Hong; Kiran, Ravi P; Remzi, Feza H; Shen, Bo

2013-09-01

The aim was to evaluate the impact of weight gain on pouch outcomes after ileostomy closure. Consecutive inflammatory bowel disease patients with ileal pouches followed up at our subspecialty Pouch Center from 2002 to 2011 were studied. The association of excessive weight gain (defined as a 15% increase the index weight) with pouch outcomes were evaluated using univariate and multivariate analyses. A total of 846 patients met inclusion criteria, with 470 (55.6%) being men. The mean age at the diagnosis of inflammatory bowel disease and at pouch surgery was 27.2 ± 11.9 years and 37.8 ± 12.8 years, respectively. Patients with weight gain more likely had mechanical or surgical complications of the pouch (18.4% versus 12.3%, P = 0.049), Crohn's disease of the pouch (30.6% versus 18.5%, P = 0.001), Pouch Center visits (2.0 [1.0-4.0] versus 2.0 [1.0-3.0], P = 0.008), and postoperative pouch-related hospitalization (21.1% versus 10.6%, P < 0.001). After a median follow-up of 9.0 (interquartile range = 4.0-14.0) years, 68 patients (8.0%) developed pouch failure. In the multivariate analysis, excessive weight gain was an independent risk factor for pouch failure with a hazard ratio of 1.69 (95% confidence interval = 1.01-2.84, P = 0.048) after adjusting for preoperative or postoperative use of anti-tumor necrosis factor biologics, postoperative use of immunosuppressants, Crohn's disease of the pouch, mechanical or surgical complications of the pouch, and postoperative pouch-associated hospitalization. Excessive weight gain after closure of the ileostomy is associated with worse pouch outcomes in patients with inflammatory bowel disease. Appropriate weight control may help improve pouch retention.

Factors associated with generic health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD): a cross-sectional study.

PubMed

Brandl, Magdalena; Böhmer, Merle M; Brandstetter, Susanne; Finger, Tamara; Fischer, Wiebke; Pfeifer, Michael; Apfelbacher, Christian

2018-02-01

Health-related quality of life (HRQOL) is impaired in chronic obstructive pulmonary disease (COPD) patients, but determining factors for HRQOL are still not unequivocal. This study measures HRQOL among patients with COPD and aims to determine factors associated with HRQOL. Data for cross-sectional analyses were obtained from the baseline of a cohort study. The study population includes adult COPD patients (disease duration ≥3 months), recruited from primary and secondary care settings in Germany, without acute psychiatric/neurologic disease (exception: affective/ anxiety disorders). HRQOL was assessed using the Short-Form 12 (SF-12) Health Survey Questionnaire, comprising a physical and mental component. Independent variables encompass socio-demographic, disease-specific, treatment-related and psychological factors. Multivariable linear regression analyses were conducted. In total, 206 COPD patients (60.7% male; mean age: 65.3 years) took part in the study. In multivariable analysis, the physical component score showed a significant negative association with the COPD Assessment Test (CAT) (P<0.001) and a higher total number of prescribed medications (P=0.001). A higher forced expiratory volume in 1 second (FEV1) value in percent predicted was significantly related to the physical component score in a positive manner (P=0.006). The mental component score was significantly associated with elevated patient-reported symptoms of anxiety (P=0.002) or depression (P<0.001), measured by the hospital anxiety and depression scale (HADS) in a negative way. Like for the physical component score (P<0.001), a worse CAT score was significantly associated with a lower mental component score (P=0.033). Focusing on patient reported outcomes and screening for depression and anxiety with potential successive treatment might be promising approaches to improve HRQOL in patients with COPD.