Showing papers by "University of Ioannina published in 2009"

The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration

Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

STrengthening the REporting of Genetic Association Studies (STREGA): An Extension of the STROBE Statement

Abstract: Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies

Abstract: Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.

Epileptic Seizure Detection in EEGs Using Time–Frequency Analysis

Abstract: The detection of recorded epileptic seizure activity in EEG segments is crucial for the localization and classification of epileptic seizures. However, since seizure evolution is typically a dynamic and nonstationary process and the signals are composed of multiple frequencies, visual and conventional frequency-based methods have limited application. In this paper, we demonstrate the suitability of the time-frequency ( t-f) analysis to classify EEG segments for epileptic seizures, and we compare several methods for t- f analysis of EEGs. Short-time Fourier transform and several t-f distributions are used to calculate the power spectrum density (PSD) of each segment. The analysis is performed in three stages: 1) t-f analysis and calculation of the PSD of each EEG segment; 2) feature extraction, measuring the signal segment fractional energy on specific t-f windows; and 3) classification of the EEG segment (existence of epileptic seizure or not), using artificial neural networks. The methods are evaluated using three classification problems obtained from a benchmark EEG dataset, and qualitative and quantitative results are presented.

Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses?

Abstract: Background Results from apparently conclusive meta-analyses may be false. A limited number of events from a few small trials and the associated random error may be under-recognized sources of spurious findings. The information size (IS, i.e. number of participants) required for a reliable and conclusive meta-analysis should be no less rigorous than the sample size of a single, optimally powered randomized clinical trial. If a meta-analysis is conducted before a sufficient IS is reached, it should be evaluated in a manner that accounts for the increased risk that the result might represent a chance finding (i.e. applying trial sequential monitoring boundaries). Methods We analysed 33 meta-analyses with a sufficient IS to detect a treatment effect of 15% relative risk reduction (RRR). We successively monitored the results of the meta-analyses by generating interim cumulative meta-analyses after each included trial and evaluated their results using a conventional statistical criterion (a ¼ 0.05) and two-sided Lan-DeMets monitoring boundaries. We examined the proportion of false positive results and important inaccuracies in estimates of treatment effects that resulted from the two approaches.

Repeatability of published microarray gene expression analyses.

Abstract: Given the complexity of microarray-based gene expression studies, guidelines encourage transparent design and public data availability. Several journals require public data deposition and several public databases exist. However, not all data are publicly available, and even when available, it is unknown whether the published results are reproducible by independent scientists. Here we evaluated the replication of data analyses in 18 articles on microarray-based gene expression profiling published in Nature Genetics in 2005-2006. One table or figure from each article was independently evaluated by two teams of analysts. We reproduced two analyses in principle and six partially or with some discrepancies; ten could not be reproduced. The main reason for failure to reproduce was data unavailability, and discrepancies were mostly due to incomplete data annotation or specification of data processing and analysis. Repeatability of published microarray studies is apparently limited. More strict publication rules enforcing public data availability and explicit description of data processing and analysis should be considered.

Meta-analysis in genome-wide association studies

Abstract: The advent of genome-wide association studies has allowed considerable progress in the identification and robust replication of common gene variants that confer susceptibility to common diseases and other phenotypes of interest. These genetic effect sizes are almost invariably moderate to small in magnitude and single studies, even if large, are underpowered to detect them with confidence. Meta-analysis of many genome-wide association studies improves the power to detect more associations, and to investigate the consistency or heterogeneity of these associations across diverse datasets and study populations. In this review, we discuss the key methodological issues in the set-up, information gathering and processing, and analysis of meta-analyses of genome-wide association datasets. We illustrate, as an example, the application of meta-analysis methods in the elucidation of common genetic variants associated with Type 2 diabetes. Finally, we discuss the prospects and caveats for future application of meta-...

Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses

Abstract: Meta-analysis is an important research design for appraising evidence and guiding medical practice and health policy. [1][1] Meta-analyses draw strength from combining data from many studies. However, even if perfectly done with perfect data, a single meta-analysis that addresses 1 treatment

The impact of “soft” and “hard” TQM elements on quality management results

Abstract: Purpose – The purpose of this paper is to explore the relationships between “soft” and “hard” TQM elements and quality management results.Design/methodology/approach – Empirical data were drawn from 370 Greek companies using the questionnaire method. Confirmatory Factor Analysis was used to examine constructs' reliability and validity, while the relationships between them were examined through Structural Equation Modelling.Findings – The study proved that quality improvement and the consolidation of the company's market position are influenced mainly by adopting “soft” TQM elements and secondarily “hard” TQM elements.Research limitations/implications – The fact that the study was based on quality managers' perceptions and the participation of companies from all sectors creates limitations, but also future research orientations.Practical implications – To achieve benefits and obtain a competitive advantage, which is of major importance for the sustainability of a company, quality design, control and improv...

Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement

Abstract: Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Boundary value problems for differential equations with fractional order and nonlocal conditions

Abstract: In this paper, we establish sufficient conditions for the existence of solutions for a class of boundary value problem for fractional differential equations involving the Caputo fractional derivative and nonlocal conditions.

Assessment of Claims of Improved Prediction Beyond the Framingham Risk Score

Abstract: Context With heightened interest in predictive medicine, many studies try to document information that can improve prediction of major clinical outcomes. Objective To evaluate the reported design and analysis of studies that examined whether additional predictors improve predictive performance when added to the Framingham risk score (FRS), one of the most widely validated and cited clinical prediction scores. Study Selection Two independent investigators searched 1908 articles citing the article that described the FRS in 1998 until September 2009 through the ISI Web of Knowledge database. Articles were eligible if they included any analyses comparing the predictive performance of the FRS vs the FRS plus some additional predictor for a prospectively assessed outcome. Data Analyses We recorded information on FRS calculation, modeling of additional predictors, outcomes assessed, population evaluated, subgroup analysis documentation, and flaws in the methods that may have affected the reported improvements in predictive ability. We also evaluated the correlation of reported design and analysis features with the predictive model discrimination and improvements with the additional predictors. Results We evaluated 79 eligible articles. Forty-nine studies (62%) did not calculate the FRS as it has been proposed, 15 (19%) modeled the additional predictor in more than 1 way and presented only the best-fit or area-under-the-curve (AUC) results for only 1 model, 41 (52%) did not examine the original outcome that the FRS was developed for, 33 (42%) studied a population different from what the FRS was intended for, and 25 (32%) claimed improved prediction in 1 subgroup but only 7 (9%) formally tested subgroup differences. Evaluation of independence in multivariable regressions, discrimination in AUC, calibration, and reclassification were reported in 77, 36, 7, and 7 studies, respectively, but these methods were adequately documented in only 60, 13, 4, and 2 studies, respectively. Overall, 63 studies (80%) claimed some improved prediction. Increase in AUC was larger when the predictive performance of the FRS was lower (ρ = −0.57, P Conclusion The majority of examined studies claimed that they found factors that could offer additional predictive value beyond what the FRS could achieve; however, most had flaws in their design, analyses, and reporting that cast some doubt on the reliability of the claims for improved prediction.

Replication in Genome-Wide Association Studies

Abstract: Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication; issues of heterogeneity; advantages and disadvantages of different methods of data synthesis across multiple studies; frequentist vs. Bayesian inferences for replication; and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies.

Collaborative Meta-analysis: Associations of 150 Candidate Genes With Osteoporosis and Osteoporotic Fracture

Abstract: Although variations in 150 genes have been tested for their influence on bone mineral density (BMD), they have not been tested for replication in large studies that assess all common genetic variat...

A Survey of Extract–Transform–Load Technology

Abstract: The software processes that facilitate the original loading and the periodic refreshment of the data warehouse contents are commonly known as Extraction-Transformation-Loading (ETL) processes. The intention of this survey is to present the research work in the field of ETL technology in a structured way. To this end, we organize the coverage of the field as follows: (a) first, we cover the conceptual and logical modeling of ETL processes, along with some design methods, (b) we visit each stage of the E-T-L triplet, and examine problems that fall within each of these stages, (c) we discuss problems that pertain to the entirety of an ETL process, and, (d) we review some research prototypes of academic origin. [Article copies are available for purchase from InfoSci-on-Demand.com]

Heartbeat Time Series Classification With Support Vector Machines

Abstract: In this study, heartbeat time series are classified using support vector machines (SVMs). Statistical methods and signal analysis techniques are used to extract features from the signals. The SVM classifier is favorably compared to other neural network-based classification approaches by performing leave-one-out cross validation. The performance of the SVM with respect to other state-of-the-art classifiers is also confirmed by the classification of signals presenting very low signal-to-noise ratio. Finally, the influence of the number of features to the classification rate was also investigated for two real datasets. The first dataset consists of long-term ECG recordings of young and elderly healthy subjects. The second dataset consists of long-term ECG recordings of normal subjects and subjects suffering from coronary artery disease.

Carcinoma of unknown primary (CUP)

Abstract: Carcinoma of unknown primary (CUP) is one of the 10 most frequent cancers worldwide. It constitutes 3-5% of all human malignancies. Patients with CUP present with metastases without an established primary site. CUP manifests as an heterogeneous group of mainly epithelial cancers recognised by distinct clinicopathological entities. The diagnostic work-up includes extensive histopathology investigations and modern imaging technology. Nevertheless, the primary tumour remains undetected most of the time. Molecular diagnosis with DNA microarrays demonstrates high sensitivity, but its prognostic contribution is still uncertain. Certain clinicopathological CUP entities are considered as favourable sub-sets responding to systemic platinum-based chemotherapy or managed by locoregional treatment. These sub-sets are: the poorly differentiated carcinomas involving the mediastinal-retroperitoneal nodes, peritoneal papillary serous adenocarcinomatosis in females, poorly differentiated neuroendocrine carcinomas, isolated axillary node adenocarcinomas in females or cervical nodal involvement by a squamous cell carcinoma. Patients who belong to the non-favourable sub-sets have a worse prognosis.

Reporting and interpretation of SF-36 outcomes in randomised trials: systematic review

Abstract: Objective To determine how often health surveys and quality of life evaluations reach different conclusions from those of primary efficacy outcomes and whether discordant results make a difference in the interpretation of trial findings. Design Systematic review. Data sources PubMed, contact with authors for missing information, and author survey for unpublished SF-36 data. Study selection Randomised trials with SF-36 outcomes (the most extensively validated and used health survey instrument for appraising quality of life) that were published in 2005 in 22 journals with a high impact factor. Data extraction Analyses on the two composite and eight subdomain SF-36 scores that corresponded to the time and mode of analysis of the primary efficacy outcome. Results Of 1057 screened trials, 52 were identified as randomised trials with SF-36 results (66 separate comparisons). Only eight trials reported all 10 SF-36 scores in the published articles. For 21 of the 66 comparisons, SF-36 results were discordant for statistical significance compared with the results for primary efficacy outcomes. Of 17 statistically significant SF-36 scores where primary outcomes were not also statistically significant in the same direction, the magnitude of effect was small in six, moderate in six, large in three, and not reported in two. Authors modified the interpretation of study findings based on SF-36 results in only two of the 21 discordant cases. Among 100 additional randomly selected trials not reporting any SF-36 information, at least five had collected SF-36 data but only one had analysed it. Conclusions SF-36 measurements sometimes produce different results from those of the primary efficacy outcomes but rarely modify the overall interpretation of randomised trials. Quality of life and health related survey information should be utilised more systematically in randomised trials.

Central and peripheral nervous system toxicity of common chemotherapeutic agents

Abstract: Central and peripheral nervous system toxicity are frequent complications of most chemotherapy regimens, often leading to reduction of dosages or cessation of the responsible drugs. However, sometimes the afflicted toxicity may not be reversible, especially if it is not recognized early, further compromising the quality of life of the cancer patients. The most common chemotherapeutic agents that might cause CNS toxicity manifested as encephalopathy of various severities include methotrexate, vincristine, ifosfamide, cyclosporine, fludarabine, cytarabine, 5-fluorouracil, cisplatin and the interferons (alpha > beta). Involvement of the peripheral nervous system manifested as distal peripheral neuropathy results after therapy with cisplatin, vincristine, taxanes, suramin and thalidomide. Although several compounds have been proposed as neuroprotective agents, few have been shown to be active against the chemotherapy induced neurotoxicity.