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Modifications of sleep EEG induced by chronic vagus nerve stimulation in patients affected by refractory epilepsy.

OBJECTIVE: The aim of this study was to evaluate the impact of chronic vagus nerve stimulation (VNS) on sleep/wake background EEG and interictal epileptiform activity (IEA) of patients with medically refractory epilepsy. METHODS: From a broader sample of 10 patients subjected to baseline and treatment polysomnographies, spectral analysis and IEA count have been performed on 6 subjects' recordings, comparing the results by means of statistical analysis. RESULTS: An overall increase in EEG total power after VNS has been observed, more marked in NREM sleep; collapsing EEG power spectra into 5 frequency bands, we have found a statistically significant increase in delta and theta in NREM sleep, and of alpha in wakefulness and REM sleep. The incidence of IEA is diminished, although not significantly; only the duration of discharges is significantly diminished. CONCLUSIONS AND SIGNIFICANCE: Long-term VNS produces an enhancement in sleep EEG power of medically refractory epileptic patients. These results may be related to a better structured composition of EEG, and it is possible that chronic VNS may have a major role in enhancing the brain's ability to generate an electrical activity.

Adult↗

Meta-analysis.

Systematic reviews use explicit and reproducible criteria to assemble, appraise, and combine articles with a minimum of bias. Meta-analysis is a form of systematic review that uses statistical techniques to derive quantitative estimates of the magnitude of treatment effects and their associated precision. Valid meta-analyses address focused questions, use appropriate criteria to select articles, assess the quality and combinability of articles, provide graphic and numeric summaries, consider potential biases, and can be generalized to a meaningful target population. The rate difference, or absolute risk reduction, is the preferred measure of clinical effect size; the reciprocal tells the number needed to treat for one additional favorable outcome. The benefits of meta-analysis over individual trials include greater precision, increased statistical power, and the ability to identify and explore diversity among studies. Threats to validity include heterogeneity, citation bias, publication bias, language bias, and variations in study quality. Because meta-analysis defines rational treatment expectations at a population level, it is an adjunct to, not a substitute for, clinical judgment in the care of individual patients.

Humans↗

Methodological issues in case-control studies: validity and power of various design/analysis strategies.

Computer stimulations have been used to estimate the efficiency, as measured by the statistical power, of various combinations of design and analysis strategies for case-control studies. Conditions under which the various forms of analysis yield consistent relative risk estimators are derived for the general model. The results indicate that the loss of efficiency resulting from the use of a less than optimum design or analysis strategy in many real life situations is small. Practical considerations are of more importance than theoretical statistical ones in deciding upon appropriate strategies. It is concluded that matching is rarely, if ever, justified in most case-control studies of chronic diseases.

Adult↗

Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials.

BACKGROUND: Although it is widely believed that the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine). METHOD: Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512). Response and remission rates were compared at week 8 or endpoint in both the intent-to-treat sample, using the last-observation-carried-forward (LOCF) method to account for attrition, and the observed cases. Tolerability data, including incidence of sexual side effects, were also compared. RESULTS: The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI (63% and 47%) groups were similar; both active therapies were superior to placebo (51% and 36%; all comparisons, p < .001). The same pattern of results was demonstrated on the observed cases analyses. Although bupropion and SSRIs were generally well tolerated, SSRI therapy resulted in significantly higher rates of sexual side effects as compared to both bupropion and placebo. SSRIs were also associated with more somnolence and diarrhea, and bupropion was associated with more dry mouth. CONCLUSION: Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.

Antidepressive Agents, Second-Generation↗

The statistical analysis of concurrent detection ratings.

The concurrent detection task is a powerful method for assessing interactions in the processing of two sensory signals. On each trial, a stimulus is presented that is composed of one, both, or neither signal, and the observer makes a detection rating for each stimulus. A classical bivariate signal-detection analysis applies to these data, but is limited by its inability to differentiate certain types of sensory interactions from more cognitive components, and by the lack of an associated testing procedure. The present paper presents an alternative analysis, based on the contingency table of sensory ratings. Six classes of effect can be distinguished and tested: (1) simple response bias, (2) detection of the two signals, (3) interference of each signal on the response to the other signal, (4) sensory and response correlation, (5) bivariate response biases, and (6) higher order association. Complete computational detail is provided.

Attention↗

Survival analysis to estimate association between short-term mortality and air pollution.

BACKGROUND: Ecologic studies are commonly used to report associations between short-term air pollution and mortality. In such studies, the unit of observation is the day rather than the individual. Moreover, individual data on the subjects are rarely available, which limits the assessment of individual risk factors. These associations can also be investigated using case-crossover studies. However, by definition, individual risk factors are not studied, and such studies analyze only dead subjects, which limits the statistical power. OBJECTIVE: We suggest that the survival analysis is more suitable when cohorts are examined with a time-dependent ecologic exposure. To our knowledge, to date this type of analysis has never been proposed. DESIGN, PARTICIPANTS, MEASUREMENTS: In the present study we used a Cox proportional hazards model to investigate the distribution over time of the short-term effect of black smoke and sulfur dioxide in 439 nonaccidental and 158 cardiorespiratory deaths among the 1,469 subjects of the Personnes Agées QUID (PAQUID) cohort in Bordeaux, France. The model has a delayed entry and a polynomial distributed lag from 0 to 5 days. Results are adjusted for individual risk factors, temperature, relative humidity, weekday, season, influenza epidemics, and a time function to control temporal trends. RESULTS: We identified a positive and significant association between cardiorespiratory mortality and black smoke, with a 24% increase in deaths 3 days after a 10-microg/m3 increase in black smoke (95% confidence interval, 4-47%). CONCLUSIONS: We conclude that the Cox proportional hazards model with time-dependent covariates is very suitable to investigate simultaneously the short-term effect of air pollution on health and the effect of individual risk factors on a cohort study.

Aged↗

The efficacy of low-power lasers in tissue repair and pain control: a meta-analysis study.

OBJECTIVE: We used statistical meta-analysis to determine the overall treatment effects of laser phototherapy on tissue repair and pain relief. BACKGROUND DATA: Low-power laser devices were first used as a form of therapy more than 30 years ago. However, their efficacy in reducing pain or promoting tissue repair remains questionable. METHODS: Following a literature search, studies meeting our inclusion criteria were identified and coded. Then, the effect size of laser treatment, that is, Cohen's d, was calculated from each study using standard meta-analysis procedures. RESULTS: Thirty-four peer-reviewed papers on tissue repair met our inclusion criteria and were used to calculate 46 treatment effect sizes. Nine peer-reviewed papers on pain control met the inclusion criteria and were used to calculate nine effect sizes. Meta-analysis revealed a positive effect of laser phototherapy on tissue repair (d = +1.81; n = 46) and pain control (d = +1.11; n = 9). The positive effect of treatment on specific indices of tissue repair was evident in the treatment effect sizes determined as follows: collagen formation (d = +2.78), rate of healing (d = +1.57), tensile strength (d = +2.13), time needed for wound closure (d = +0.76), tensile stress (d = +2.65), number and rate of degranulation of mast cells (d = +1.87), and flap survival (d = +1.95). Further, analysis revealed the positive effects of various wavelengths of laser light on tissue repair, with 632.8 nm having the highest treatment effect (d = +2.44) and 780 nm the least (d = 0.60). The overall treatment effect for pain control was positive as well (d = +1.11). The fail-safe number-that is, the number of studies in which laser phototherapy has negative or no effect-needed to nullify the overall outcome of this analysis was 370 for tissue repair and 41 for pain control. CONCLUSIONS: These findings mandate the conclusion that laser phototherapy is a highly effective therapeutic armamentarium for tissue repair and pain relief.

Female↗

Data explorer: a prototype expert system for statistical analysis.

The inadequate analysis of medical research data, due mainly to the unavailability of local statistical expertise, seriously jeopardizes the quality of new medical knowledge. Data Explorer is a prototype Expert System that builds on the versatility and power of existing statistical software, to provide automatic analyses and interpretation of medical data. The system draws much of its power by using belief network methods in place of more traditional, but difficult to automate, classical multivariate statistical techniques. Data Explorer identifies statistically significant relationships among variables, and using power-size analysis, belief network inference/learning and various explanatory techniques helps the user understand the importance of the findings. Finally the system can be used as a tool for the automatic development of predictive/diagnostic models from patient databases.

Artificial Intelligence↗

Advances in statistical methods for substance abuse prevention research.

The paper describes advances in statistical methods for prevention research with a particular focus on substance abuse prevention. Standard analysis methods are extended to the typical research designs and characteristics of the data collected in prevention research. Prevention research often includes longitudinal measurement, clustering of data in units such as schools or clinics, missing data, and categorical as well as continuous outcome variables. Statistical methods to handle these features of prevention data are outlined. Developments in mediation, moderation, and implementation analysis allow for the extraction of more detailed information from a prevention study. Advancements in the interpretation of prevention research results include more widespread calculation of effect size and statistical power, the use of confidence intervals as well as hypothesis testing, detailed causal analysis of research findings, and meta-analysis. The increased availability of statistical software has contributed greatly to the use of new methods in prevention research. It is likely that the Internet will continue to stimulate the development and application of new methods.

Humans↗

Regression estimator in ranked set sampling.

Ranked set sampling (RSS) utilizes inexpensive auxiliary information about the ranking of the units in a sample to provide a more precise estimator of the population mean of the variable of interest Y, which is either difficult or expensive to measure. However, the ranking may not be perfect in most situations. In this paper, we assume that the ranking is done on the basis of a concomitant variable X. Regression-type RSS estimators of the population mean of Y will be proposed by utilizing this concomitant variable X in both the ranking process of the units and the estimation process when the population mean of X is known. When X has unknown mean, double sampling will be used to obtain an estimate for the population mean of X. It is found that when X and Y jointly follow a bivariate normal distribution, our proposed RSS regression estimator is more efficient than RSS and simple random sampling (SRS) naive estimators unless the correlation between X and Y is low (/rho/ < 0.4). Moreover, it is always superior to the regression estimator under SRS for all rho. When normality does not hold, this approach could still perform reasonably well as long as the shape of the distribution of the concomitant variable X is only slightly departed from symmetry. For heavily skewed distributions, a remedial measure will be suggested. An example of estimating the mean plutonium concentration in surface soil on the Nevada Test Site, Nevada, U.S.A., will be considered.

Biometry↗

The new genetics of schizophrenia.

Despite the genetic and phenotypic complexity of schizophrenia, much progress has been made. Research has largely excluded the possibility that genes of major effect exist; linkage analysis has provided independently replicated evidence for genes of moderate effect on several chromosomal regions. Association studies suggest that alleles of at least two genes, those encoding D3 and 5HT2A, confer a small rise in susceptibility to schizophrenia, and there are convergent findings from several different lines of research implicating regions such as 22q11, although no specific causative genes for schizophrenia have been definitively identified yet. There are strong grounds for optimism as larger samples are collected to increase the power of studies, and novel methods of statistical analysis and large-scale genotyping of SNPs are developed and refined. Although the difficulties and challenges of genetics research into schizophrenia are formidable, the devastating personal and social consequences of the illness make it imperative that these challenges are faced, because the identification of susceptibility genes for schizophrenia would result in further productive neurobiologic research and ultimately improvements in the prevention and treatment of schizophrenia.

Adoption↗

Numerical approaches for quantitative analysis of two-dimensional maps: a review of commercial software and home-made systems.

The present review attempts to cover a number of methods that have appeared in the last few years for performing quantitative proteome analysis. However, due to the large number of methods described for both electrophoretic and chromatographic approaches, we have limited this review to conventional two-dimensional (2-D) map analysis which couples orthogonally a charge-based step (isoelectric focusing) to a size-based separation step (sodium dodecyl sulfate-electrophoresis). The first and oldest method applied to 2-D map data reduction is based on statistical analysis performed on sets of gels via powerful software packages, such as Melanie, PDQuest, Z3 and Z4000, Phoretix and Progenesis. This method calls for separately running a number of replicas for control and treated samples. The two sets of data are then merged and compared via a number of software packages which we describe. In addition to commercially-available systems, a number of home made approaches for 2-D map comparison have been recently described and are also reviewed. They are based on fuzzyfication of the digitized 2-D gel image coupled to linear discriminant analysis, three-way principal component analysis or a combination of principal component analysis and soft-independent modeling of class analogy. These statistical tools appear to perform well in differential proteomic studies.

Cluster Analysis↗

Scaling behavior in mitochondrial redox fluctuations.

Scale-invariant long-range correlations have been reported in fluctuations of time-series signals originating from diverse processes such as heart beat dynamics, earthquakes, and stock market data. The common denominator of these apparently different processes is a highly nonlinear dynamics with competing forces and distinct feedback species. We report for the first time an experimental evidence for scaling behavior in NAD(P)H signal fluctuations in isolated mitochondria and intact cells isolated from the liver of a young (5-month-old) mouse. Time-series data were collected by two-photon imaging of mitochondrial NAD(P)H fluorescence and signal fluctuations were quantitatively analyzed for statistical correlations by detrended fluctuation analysis and spectral power analysis. Redox [NAD(P)H / NAD(P)(+)] fluctuations in isolated mitochondria and intact liver cells were found to display nonrandom, long-range correlations. These correlations are interpreted as arising due to the regulatory dynamics operative in Krebs' cycle enzyme network and electron transport chain in the mitochondria. This finding may provide a novel basis for understanding similar regulatory networks that govern the nonequilibrium properties of living cells.

Animals↗

The use of epidemiologic approaches and meta-analysis to determine mineral element requirements.

With a new focus on long-term health effects of nutrient intake as well as the traditional concerns of preventing deficiency and maintaining tissue saturation, epidemiologic studies which identify diet and health relationships have become important to debates on defining nutrient requirements. Epidemiologic studies include descriptive surveys, case-control studies, cohort studies, and intervention studies. National dietary intake survey data have always played a role in defining intake amounts which are feasible and which are associated with no clearly apparent health problem. A growing number of large epidemiologic cohort studies have provided new evidence of preventive effects of specific nutrients on chronic diseases. The question of how that information should be used in setting requirements is still unresolved. Because one epidemiologic study alone cannot prove a causal relationship, and because small studies often lack sufficient power to clearly establish statistical significance, meta-analysis is sometimes used to combine results from many studies to obtain an overall quantitative result. It has been most effectively used with sets of clinical trials. Meta-analysis of multiple observational studies is usually difficult because of variations in design, methodology of data collection and form of the variables; its use has been seriously challenged. Careful review of the totality of epidemiologic studies completed on specific nutrient and health or functional outcome is important to defining future research priorities and designs, and can inform the definition of nutrient requirements when used carefully and in conjunction with the wider body of scientific evidence.

Diet↗

Effect of crossover on the statistical power of randomized studies.

Randomized studies involving long-term follow-up are vulnerable to the effects of unplanned crossover. In surgical studies, such crossover usually occurs when control patients become more symptomatic and undergo operation. In several large studies of coronary bypass grafting, crossover ranged from 25% to 38%. The most common way of dealing with this problem is to apply the "intention-to-treat" principle, which analyzes such crossovers with their originally assigned groups. Besides the logical problem of counting a control patient who actually undergoes operation as "nonsurgical," a more subtle problem arises in terms of statistical power. When statistical power is low, a truly effective treatment may be mistakenly labeled as no better than control, causing a potentially valuable form of therapy to be ignored or discarded. This analysis demonstrates that crossover may have a profound effect on the statistical power of randomized studies and presents a method for predicting the effect of such crossover on statistical power.

Coronary Artery Bypass↗

Statistical properties of affected sib-pair linkage tests.

Genetic linkage analysis is a powerful tool for the identification of disease susceptibility loci. Among the most commonly applied genetic linkage strategies are affected sib-pair tests, but the statistical properties of these tests have not been well characterized. Here, we present a study of the distribution of affected sib-pair tests comparing the type I error rate and the power of the mean test and the proportion test, which are the most commonly used, along with a novel exact test. In contrast to existing literature, our findings showed that the mean and proportion tests have inflated type I error rates, especially when used with small samples. We developed and applied corrections to the tests which provide an excellent adjustment to the type I error rate for both small and large samples. We also developed a novel approach to identify the areas of higher power for the mean test versus the proportion test, providing a wider and simpler comparison with fewer assumptions about parameter values than existing approaches require.

Alleles↗

Biological master games: using biologists' reasoning to guide algorithm development for integrated functional genomics.

We review some powerful new algorithms that build on the intuitive biological interpretation techniques for statistical analysis of functional genomics experiments. Although they were originally designed for transcriptomics, we argue that these algorithms are applicable to any type of -omics study (transcriptomics, proteomics, metabolomics). Rank Products (RP), a strictly non-parametric test statistic to detect differentially regulated elements (genes, proteins, metabolites) in genome-wide screens. RP is particularly powerful for noisy data and low numbers of replicates and makes full use of the availability of a large number of parallel measurements that is typical of modern large-scale experiments. Iterative Group Analysis (iGA), a statistical method that makes the transition from regulated single elements to significant classes of elements, and thus provides an automatic functional annotation of an experiment. Graph-based iGA (GiGA), an extension of iGA that combines experimental data with a broad variety of biological annotations to highlight physiologically relevant regions in a given "evidence graph" (e.g., metabolic networks, signaling pathway diagrams, protein interaction maps). The sequential application of these techniques yields an increasingly abstract interpretation of experimental data that is at the same time quantitative, statistically rigorous, and biologically significant. The results can be used either as helpful tools to guide data visualization and exploration, or as the input for downstream computational applications in a systems biology framework.

Algorithms↗

A knowledge-based system for data analysis and interpretation.

Traditionally, statistical packages are employed to derive or infer facts about a Universe of Discourse through data analysis and interpretation. It is analysis that serves to transform data into information. Statistical packages provide the users with relatively easy-to-use and powerful mechanics of data analysis, but up to now they do not provide much help with the design and strategies of the analysis. As such, there is a risk of misuse of these packages by statistically inexperienced users. We propose the use of knowledge-based interfaces to support this category of users in statistical evaluations. This paper discusses our experiences from the implementation of a knowledge-based system called MAXITAB. It provides guidance in the processes of data analysis and interpretation and has been programmed as an interface to the statistical package MINITAB.

Data Interpretation, Statistical↗