一般线性模型在药物配伍试验中的应用

目的 建立药物配伍试验数据的分析模型。方法 用一般线性模型(General Linear，GLM)分析文献报道的药物配伍试验数据。结果 方差分析表可以指出那些因素对模型有显著影响；同类亚群表可将因素内平均值无显著差异者归入同一亚群，即同一亚群内的所有平均值相互之间的差弄无显著性(P＞0．05)，而不同亚群之间则有显著性差异(P＜0．05)。结论 该模型可用于药物配伍试验的数据分析。     

Mixed General Linear Model Analysis of Quantitative Electroencephalographic (qEEG) Data

ABSTRACT

This paper describes a mixed general linear analysis of the quantitative electroencephalogram (qEEG). The modeling is similar to regression, which builds a regression or ‘best-fit’ model for the data structure but, in addition, provides for correlations between observations. A mixed linear model states that data consists of two parts: fixed effects and random effects. Fixed effects determine the expected values of the observations, while random effects account for the stochastic deviations from these expected values both between and within individuals. Since errors are independent between subjects, the deviations from the expected values may also be modeled using a repeated measures approach. The term ‘repeated measures’ in this model refers to data with multiple observations from one specific source. It is reasonable to assume that these observations from the same source are correlated, even if only slightly, in some measurable way. Consequently, statistical analysis of repeated measures data gives a more accurate prediction capability when the issue of covariation between these measures is addressed.

With mixed model methodology now available (e.g., the mixed procedure [Mixed PROC] of the SAS® system), the covariance structure can be incorporated into the statistical model. Disregarding potential random effects not specific to single individuals and absorbing potential within-subject random effects into the covariance matrix allows one to work with a simplified model.

The use of a mixed procedure and its method of modeling the data structure appear to provide an accurate and objective method of analysis resulting in quantifiable equations for testing predictions. Essentially, this method allows the physiological pattern of each individual in the study, not related to any other variable, to be represented and accounted for in the model. Several comparative examples will be used to highlight the information that can be hidden in data structures depending on the type of statistical analysis used.     

Predicting healthcare expenditure by multimorbidity groups

Objectives

This article has two main purposes. Firstly, to model the integrated healthcare expenditure for the entire population of a health district in Spain, according to multimorbidity, using Clinical Risk Groups (CRG). Secondly, to show how the predictive model is applied to the allocation of health budgets.

Practical model description of peripheral neural excitation in cochlear implant recipients: 3. ECAP during bursts and loudness as function of burst duration

In this, the third paper of the series, the loudness of low-rate bursts of electrical pulses was measured as a function of the burst duration, in subjects implanted with the Nucleus^® 24 cochlear implant system (three with straight and two with Contour™ electrode arrays). In order to help distinguish between the contributions of peripheral and more central effects, the ECAP was recorded to the individual pulses comprising the bursts, using the Neural Response Telemetry™ (NRT™) system. At a pulse rate of 250 pulses/s, the ECAP amplitude did not decrease greatly during the bursts: the mean reduction factor was 0.89. The time-constant for summation of the loudness contributions from the pulses comprising a burst was found to be larger than that associated with normal hearing. In addition, the first pulse of a pulse train was found to contribute much more to the overall loudness than did the subsequent pulses, although a corresponding difference was not observed in the ECAP recordings. These results establish a necessary connection between the essentially single-pulse model, developed in the fourth and fifth papers of the series, and the psychophysical data for pulse bursts, but they also have broader implications.     

Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology

Exposure to childhood trauma may induce persistent changes in Hypothalamic-Pituitary-Adrenal (HPA)-axis functioning even in the absence of current psychopathology. Because previous studies did not systematically exclude subjects with lifetime psychiatric morbidity, prevalent psychopathology may have confounded the association. In this study we investigated whether women exposed to childhood trauma, but without a history of psychiatric disorders, show alterations in HPA-axis functioning. We included 10 women exposed to significant childhood trauma and 12 non-exposed women. All women were between 29 and 64 years old, mentally and physically healthy, and without current or lifetime psychopathology. HPA-axis functioning was assessed as 1) basal activity with salivary cortisol patterns over 8 time points on two consecutive sampling days and 2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7 time points after the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) challenge test. Basal salivary cortisol output did not differ between trauma-exposed compared to non-exposed women. Significantly blunted plasma cortisol and ACTH responses in response to dex/CRH administration were found in the trauma-exposed compared to the non-exposed women (F(1,20) = 5.08, p = 0.04 and F(1,20) = 5.23, p = 0.03 respectively). Adjusting for age, body mass index (BMI), oral contraceptive use, and menopausal status, somewhat weakened the associations for cortisol as well as ACTH (F(1,16) = 3.30, p = 0.09) and F(1,16) = 2.17, p = 0.16 respectively), but for cortisol absolute differences in point estimates were largely unaffected. Although basal cortisol patterns were similar in the two groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis reactivity in women who were free of current or lifetime psychopathology.     

Temporal changes in the spatial pattern of disease rates incorporating known risk factors

Examining the geographical pattern of temporal changes in infant mortality rates illustrates the methodological problems of documenting and understanding temporal changes in any spatial pattern of disease. Early research on geographical differences in infant mortality rates showed strong ecological correlations with socio-economic factors such as poverty rates. More recent research established relationships between individual-level socio-economic values and probabilities of death. With geographic information available at the level of individuals, it is possible to estimate the probabilities of death on a person-by-person basis from knowledge of the relationships between individual factors and socio-economic measures. These estimated probabilities provide an expected geographic pattern of deaths. The difference between the observed spatial pattern and the expected pattern is the remaining spatial variation adjusted for this knowledge. For the study area, individual factors and some socio-economic measures were available for each year of the study period. Using data from the Iowa Birth Defects Registry and the Iowa Department of Public Health (USA), I tested the stability and continuity of these cross-sectional relationships and investigated whether any temporal lags in these variables relate to the unexplained spatial variations in infant mortality rates that remain. I accounted for the 'Change of Support Problem' [Gotway C. A. & Young L. J. (2002). Combining incompatible spatial data. Journal of the American Statistical Association, 97458, 632-648] inherent in frame-based geographical analysis. The analysis involved a generalized linear model (GLM) to estimate individual risks and a Monte Carlo simulation model to generate the non-linear probability density functions for disease rates whose densities are theoretically intractable. Results show the temporal changes in the observed spatial pattern and the expected spatial pattern differ by geographic location. In conclusion such differences are the result of a combination of unexplained place-based risk and unmeasured individual risks.     

Evolution of Functional Exercise Capacity in Lung Transplant Patients With and Without Bronchiolitis Obliterans Syndrome: A Longitudinal Case–Control Study

Introduction

Bronchiolitis Obliterans Syndrome (BOS) is a debilitating disease with limited treatment options that threatens both the quality of life and long-term survival of lung transplant (LTx) recipients. This retrospective longitudinal case–control study was performed to compare the long-term functional evolution of LTx recipients with and without BOS.

An Endoscopic Transluminal Approach,Compared With Minimally Invasive Surgery,Reduces Complications and Costs for Patients With Necrotizing Pancreatitis

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The Stockholm Neonatal Family-Centered Care Study: effects on salivary cortisol in infants and their mothers

Background

Parental involvement in the care of preterm infants in neonatal intensive care units (NICUs) is common, but little is known about the effect on stress responses in mothers and infants.

Aims

The aim of this study is to evaluate the effect of family-centered care on salivary cortisol reactivity in mothers and preterm infants and the correlation between the mothers' and the preterm infants' salivary cortisol levels.

Methods

This study is part of a randomized controlled trial conducted at two level-II NICUs, including Family Care (FC), where parents were able to stay 24 h/day from admission to discharge, and Standard Care (SC). To investigate the cortisol response, saliva was collected from 289 preterm infants and their mothers before and after a diaper change at the time of discharge.

Results

No significant differences were found between the two groups in salivary cortisol reactivity, either in mothers or in infants. The results revealed a correlation between preterm infants' and their mothers' baseline and response cortisol in the FC group: r = 0.31 (p = 0.001) and r = 0.24 (p = 0.01), respectively. Such correlation was not observed in the SC group: r = 0.14 (p = 0.14) and r = 0.18 (p = 0.07), respectively.

Conclusions

Family-centered care had no effect on salivary cortisol reactivity during diaper change. However, sharing the same environment may increase the concordance between preterm infants' and their mothers' salivary cortisol levels.