Can we improve the statistical analysis of stroke trials? Statistical re-analysis of functional outcomes in stroke trials

Background: Most large acute stroke trials have been neutral. Functional outcome is usually analysed using a yes or no answer, e.g. death or dependency vs. independence. We assessed which statistical approaches are most efficient in analysing outcomes from stroke trials. Methods: Individual patient data from acute, rehabilitation and stroke unit trials studying the effects of interventions which alter functional outcome were assessed. Outcomes included modified Rankin Scale, Barthel Index, and ‘3 questions’. Data were analysed using a variety of approaches which compare two treatment groups. The results for each statistical test for each trial were then compared. Results: Data from 55 datasets were obtained (47 trials, 54,173 patients). The test results differed substantially so that approaches which use the ordered nature of functional outcome data (ordinal logistic regression, t-test, robust ranks test, bootstrapping the difference in mean rank) were more efficient statistically than those which collapse the data into 2 groups (chi square) (ANOVA p<0.001). The findings were consistent across different types and sizes of trial and for the different measures of functional outcome. Conclusions: When analysing functional outcome from stroke trials, statistical tests which use the original ordered data are more efficient and more likely to yield reliable results. Suitable approaches included ordinal logistic regression, t-test, and robust ranks test.

Use of ordinal outcomes in vascular prevention trials: comparison with binary outcomes in published trials

Background and Purpose—Vascular prevention trials mostly count “yes/no” (binary) outcome events, eg, stroke/no stroke. Analysis of ordered categorical vascular events (eg, fatal stroke/nonfatal stroke/no stroke) is clinically relevant and could be more powerful statistically. Although this is not a novel idea in the statistical community, ordinal outcomes have not been applied to stroke prevention trials in the past. Methods—Summary data on stroke, myocardial infarction, combined vascular events, and bleeding were obtained by treatment group from published vascular prevention trials. Data were analyzed using 10 statistical approaches which allow comparison of 2 ordinal or binary treatment groups. The results for each statistical test for each trial were then compared using Friedman 2-way analysis of variance with multiple comparison procedures. Results—Across 85 trials (335 305 subjects) the test results differed substantially so that approaches which used the ordinal nature of stroke events (fatal/nonfatal/no stroke) were more efficient than those which combined the data to form 2 groups (P0.0001). The most efficient tests were bootstrapping the difference in mean rank, Mann–Whitney U test, and ordinal logistic regression; 4- and 5-level data were more efficient still. Similar findings were obtained for myocardial infarction, combined vascular outcomes, and bleeding. The findings were consistent across different types, designs and sizes of trial, and for the different types of intervention. Conclusions—When analyzing vascular events from prevention trials, statistical tests which use ordered categorical data are more efficient and are more likely to yield reliable results than binary tests. This approach gives additional information on treatment effects by severity of event and will allow trials to be smaller. (Stroke. 2008;39:000-000.)

Can we improve the statistical analysis of stroke trials? Statistical reanalysis of functional outcomes in stroke trials

Background and Purpose—Most large acute stroke trials have been neutral. Functional outcome is usually analyzed using a yes or no answer, eg, death or dependency versus independence. We assessed which statistical approaches are most efficient in analyzing outcomes from stroke trials. Methods—Individual patient data from acute, rehabilitation and stroke unit trials studying the effects of interventions which alter functional outcome were assessed. Outcomes included modified Rankin Scale, Barthel Index, and “3 questions”. Data were analyzed using a variety of approaches which compare 2 treatment groups. The results for each statistical test for each trial were then compared. Results—Data from 55 datasets were obtained (47 trials, 54 173 patients). The test results differed substantially so that approaches which use the ordered nature of functional outcome data (ordinal logistic regression, t test, robust ranks test, bootstrapping the difference in mean rank) were more efficient statistically than those which collapse the data into 2 groups (2; ANOVA, P0.001). The findings were consistent across different types and sizes of trial and for the different measures of functional outcome. Conclusions—When analyzing functional outcome from stroke trials, statistical tests which use the original ordered data are more efficient and more likely to yield reliable results. Suitable approaches included ordinal logistic regression, test, and robust ranks test.

Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction

Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10 years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1 year, median 371 days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD = 1.5, 95% confidence interval 1.1 to 2.1, p = 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD = 1.8, 95% confidence interval 1.2 to 2.6, p = 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p = 0.016). HGF showed a complementary value over NT-proBNP (p = 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP.

Use of posterior predictive assessments to evaluate model fit in multilevel logistic regression

Assessing the fit of a model is an important final step in any statistical analysis, but this is not straightforward when complex discrete response models are used. Cross validation and posterior predictions have been suggested as methods to aid model criticism. In this paper a comparison is made between four methods of model predictive assessment in the context of a three level logistic regression model for clinical mastitis in dairy cattle; cross validation, a prediction using the full posterior predictive distribution and two “mixed” predictive methods that incorporate higher level random effects simulated from the underlying model distribution. Cross validation is considered a gold standard method but is computationally intensive and thus a comparison is made between posterior predictive assessments and cross validation. The analyses revealed that mixed prediction methods produced results close to cross validation whilst the full posterior predictive assessment gave predictions that were over-optimistic (closer to the observed disease rates) compared with cross validation. A mixed prediction method that simulated random effects from both higher levels was best at identifying the outlying level two (farm-year) units of interest. It is concluded that this mixed prediction method, simulating random effects from both higher levels, is straightforward and may be of value in model criticism of multilevel logistic regression, a technique commonly used for animal health data with a hierarchical structure.

Sistema RANKL/RANK/OPG e o seu papel na reabsorção óssea na periodontite crónica

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Expressão e regulação do ligando RANK na leucemia de células T

Dissertação de Mestrado, Oncobiologia, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Probabilistic methods for seasonal forecasting in a changing climate: Cox-type regression models.

For climate risk management, cumulative distribution functions (CDFs) are an important source of information. They are ideally suited to compare probabilistic forecasts of primary (e.g. rainfall) or secondary data (e.g. crop yields). Summarised as CDFs, such forecasts allow an easy quantitative assessment of possible, alternative actions. Although the degree of uncertainty associated with CDF estimation could influence decisions, such information is rarely provided. Hence, we propose Cox-type regression models (CRMs) as a statistical framework for making inferences on CDFs in climate science. CRMs were designed for modelling probability distributions rather than just mean or median values. This makes the approach appealing for risk assessments where probabilities of extremes are often more informative than central tendency measures. CRMs are semi-parametric approaches originally designed for modelling risks arising from time-to-event data. Here we extend this original concept beyond time-dependent measures to other variables of interest. We also provide tools for estimating CDFs and surrounding uncertainty envelopes from empirical data. These statistical techniques intrinsically account for non-stationarities in time series that might be the result of climate change. This feature makes CRMs attractive candidates to investigate the feasibility of developing rigorous global circulation model (GCM)-CRM interfaces for provision of user-relevant forecasts. To demonstrate the applicability of CRMs, we present two examples for El Ni ? no/Southern Oscillation (ENSO)-based forecasts: the onset date of the wet season (Cairns, Australia) and total wet season rainfall (Quixeramobim, Brazil). This study emphasises the methodological aspects of CRMs rather than discussing merits or limitations of the ENSO-based predictors.

A demand-driven analysis of tourist accommodation price: A quantile regression of room bookings

Tourist accommodation expenditure is a widely investigated topic as it represents a major contribution to the total tourist expenditure. The identification of the determinant factors is commonly based on supply-driven applications while little research has been made on important travel characteristics. This paper proposes a demand-driven analysis of tourist accommodation price by focusing on data generated from room bookings. The investigation focuses on modeling the relationship between key travel characteristics and the price paid to book the accommodation. To accommodate the distributional characteristics of the expenditure variable, the analysis is based on the estimation of a quantile regression model. The findings support the econometric approach used and enable the elaboration of relevant managerial implications.

A survey on multi-output regression

In recent years, a plethora of approaches have been proposed to deal with the increasingly challenging task of multi-output regression. This paper provides a survey on state-of-the-art multi-output regression methods, that are categorized as problem transformation and algorithm adaptation methods. In addition, we present the mostly used performance evaluation measures, publicly available data sets for multi-output regression real-world problems, as well as open-source software frameworks.

GIS-integrated mathematical modeling of social phenomena at macro- and micro- levels—a multivariate geographically-weighted regression model for identifying locations vulnerable to hosting terrorist safe-houses: France as case study

Adaptability and invisibility are hallmarks of modern terrorism, and keeping pace with its dynamic nature presents a serious challenge for societies throughout the world. Innovations in computer science have incorporated applied mathematics to develop a wide array of predictive models to support the variety of approaches to counterterrorism. Predictive models are usually designed to forecast the location of attacks. Although this may protect individual structures or locations, it does not reduce the threat—it merely changes the target. While predictive models dedicated to events or social relationships receive much attention where the mathematical and social science communities intersect, models dedicated to terrorist locations such as safe-houses (rather than their targets or training sites) are rare and possibly nonexistent. At the time of this research, there were no publically available models designed to predict locations where violent extremists are likely to reside. This research uses France as a case study to present a complex systems model that incorporates multiple quantitative, qualitative and geospatial variables that differ in terms of scale, weight, and type. Though many of these variables are recognized by specialists in security studies, there remains controversy with respect to their relative importance, degree of interaction, and interdependence. Additionally, some of the variables proposed in this research are not generally recognized as drivers, yet they warrant examination based on their potential role within a complex system. This research tested multiple regression models and determined that geographically-weighted regression analysis produced the most accurate result to accommodate non-stationary coefficient behavior, demonstrating that geographic variables are critical to understanding and predicting the phenomenon of terrorism. This dissertation presents a flexible prototypical model that can be refined and applied to other regions to inform stakeholders such as policy-makers and law enforcement in their efforts to improve national security and enhance quality-of-life.

Structural brain connectivity and cognitive ability differences: A multivariate distance matrix regression analysis

Neuroimaging research involves analyses of huge amounts of biological data that might or might not be related with cognition. This relationship is usually approached using univariate methods, and, therefore, correction methods are mandatory for reducing false positives. Nevertheless, the probability of false negatives is also increased. Multivariate frameworks have been proposed for helping to alleviate this balance. Here we apply multivariate distance matrix regression for the simultaneous analysis of biological and cognitive data, namely, structural connections among 82 brain regions and several latent factors estimating cognitive performance. We tested whether cognitive differences predict distances among individuals regarding their connectivity pattern. Beginning with 3,321 connections among regions, the 36 edges better predicted by the individuals' cognitive scores were selected. Cognitive scores were related to connectivity distances in both the full (3,321) and reduced (36) connectivity patterns. The selected edges connect regions distributed across the entire brain and the network defined by these edges supports high-order cognitive processes such as (a) (fluid) executive control, (b) (crystallized) recognition, learning, and language processing, and (c) visuospatial processing. This multivariate study suggests that one widespread, but limited number, of regions in the human brain, supports high-level cognitive ability differences. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

Applying Least Absolute Shrinkage Selection Operator and Akaike Information Criterion Analysis to Find the Best Multiple Linear Regression Models between Climate Indices and Components of Cow’s Milk

This study focuses on multiple linear regression models relating six climate indices (temperature humidity THI, environmental stress ESI, equivalent temperature index ETI, heat load HLI, modified HLI (HLI new), and respiratory rate predictor RRP) with three main components of cow’s milk (yield, fat, and protein) for cows in Iran. The least absolute shrinkage selection operator (LASSO) and the Akaike information criterion (AIC) techniques are applied to select the best model for milk predictands with the smallest number of climate predictors. Uncertainty estimation is employed by applying bootstrapping through resampling. Cross validation is used to avoid over-fitting. Climatic parameters are calculated from the NASA-MERRA global atmospheric reanalysis. Milk data for the months from April to September, 2002 to 2010 are used. The best linear regression models are found in spring between milk yield as the predictand and THI, ESI, ETI, HLI, and RRP as predictors with p-value < 0.001 and R2 (0.50, 0.49) respectively. In summer, milk yield with independent variables of THI, ETI, and ESI show the highest relation (p-value < 0.001) with R2 (0.69). For fat and protein the results are only marginal. This method is suggested for the impact studies of climate variability/change on agriculture and food science fields when short-time series or data with large uncertainty are available.