Translating cross-lagged effects into incidence rates and risk ratios: The case of psychosocial safety climate and depression

Longitudinal studies are the gold standard of empirical work and stress research whenever experiments are not plausible. Frequently, scales are used to assess risk factors and their consequences, and cross-lagged effects are estimated to determine possible risks. Methods to translate cross-lagged effects into risk ratios to facilitate risk assessment do not yet exist, which creates a divide between psychological and epidemiological work stress research. The aim of the present paper is to demonstrate how cross-lagged effects can be used to assess the risk ratio of different levels of psychosocial safety climate (PSC) in organisations, an important psychosocial risk for the development of depression. We used available longitudinal evidence from the Australian Workplace Barometer (N?=?1905) to estimate cross-lagged effects of PSC on depression. We applied continuous time modelling to obtain time-scalable cross effects. These were further investigated in a 4-year Monte Carlo simulation, which translated them into 4-year incident rates. Incident rates were determined by relying on clinically relevant 2-year periods of depression. We suggest a critical value of PSC?=?26 (corresponding to ?1.4 SD), which is indicative of more than 100% increased incidents of persistent depressive disorder in 4-year periods compared to average levels of PSC across 4 years.     

Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial.     

Comparison of labour and birth outcomes between nulliparous women who used epidural analgesia in labour and those who did not: A prospective cohort study

ObjectiveTo compare labour and birth outcomes between nulliparous women who used versus did not use intrapartum epidural analgesia.DesignProspective cohort study.SettingTwo maternity hospitals in Ireland.PopulationA total of 1221 nulliparous women who gave birth vaginally or by emergency caesarean section.MethodsMultinomial logistic regression was used to analyse categorical outcomes, with results presented as ratios of relative risks (RRR). For dichotomous outcomes we used logistic regression, with results presented as odds ratios (OR).Main outcome measuresMode of birth, IV syntocinon use, pyrexia (≥38 °C), antibiotic treatment, first stage labour ≥10 h, second stage labour ≥2 h, blood loss (≥500 mls, ≥1000 mls), perineal trauma. Neonatal outcomes included Apgar score ≥7 at 1 min and 5 min, admission to neonatal intensive care unit, and infant feeding method.ResultsWomen using EA were more likely to require a vacuum-assisted birth (RRR 3.35, p < 0.01) or forceps-assisted birth (RRR 11.69, p < 0.01). Exposure to EA was associated with significantly greater risk of ≥10 h first (OR 6.72, p = 0.01) and ≥2 h second (OR 2.25, p < 0.01) stage labour, increased likelihood of receiving IV syntocinon (OR 9.38, p < 0.01), antibiotics (OR 2.97, p < 0.01) and a greater probability of pyrexia (OR 10.26, p < 0.01). Women who used EA were half as likely to be breastfeeding at three months postpartum (OR 0.53, p < 0.01). No differences were observed between groups in neonatal outcomes.ConclusionsOur data shows significant associations between EA use and several intrapartum outcomes.     

Using local linear kernel smoothers to test the lack of fit of nonlinear regression models

Herein, we propose a data-driven test that assesses the lack of fit of nonlinear regression models. The comparison of local linear kernel and parametric fits is the basis of this test, and specific boundary-corrected kernels are not needed at the boundary when local linear fitting is used. Under the parametric null model, the asymptotically optimal bandwidth can be used for bandwidth selection. This selection method leads to the data-driven test that has a limiting normal distribution under the null hypothesis and is consistent against any fixed alternative. The finite-sample property of the proposed data-driven test is illustrated, and the power of the test is compared with that of some existing tests via simulation studies. We illustrate the practicality of the proposed test by using two data sets.     

阅读与语篇理解的相关理论分析

阅读是外语教学和学习中的重要环节。阅读不仅是读者知识积累和经验积淀的反映,而且可以构架起作者和读者之间沟通的桥梁。掌握了语篇生成的理论基础和技巧,读者就能在阅读中驾轻就熟地理解作者的意图和观点,从而达到理解语篇的目的。     

Still-births among the offspring of male radiation workers at the Sellafield nuclear reprocessing plant: detailed results and statistical aspects

Summary. This study investigates whether there was evidence of increasing risk of still-birth with increasing paternal exposure to ionizing radiation received during employment at the Sellafield nuclear installation before the child was conceived. A significant positive association is found between the total paternal preconceptional exposure to external ionizing radiation and the risk of still-birth (after adjustment for year of birth, social class, birth order and paternal age, odds ratio at 100 mSv 1.24 (95% confidence interval 1.04–1.45)). A summary of the principal scientific findings of this study has been published in the Lancet . This paper describes in detail the statistical methods that were used in the investigation and presents the results in full.     

运动元记忆训练对元记忆水平和动作记忆的影响

通过2个月的运动元记忆训练,检验其对非体育专业学生元记忆水平和动作记忆成绩的影响.结果显示运动元记忆训练能显著提高大学生运动记忆策略和记忆监控水平;结果还表明训练能明显提高大学生的艺术体操和健美操动作记忆成绩(表现在动作数量上),而且艺术体操动作记忆的训练效应大于健美操.     

Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

Efficient designs based on orthogonal arrays of type I and type II for experiments using units ordered over time or space

For a wide variety of applications, experiments are based on units ordered over time or space. Models for these experiments generally may include one or more of: correlations, systematic trends, carryover effects and interference effects. Since the standard optimal block designs may not be efficient in these situations, orthogonal arrays of type I and type II, which were introduced in 1961 by C.R. Rao [Combinatorial arrangements analogous to orthogonal arrays, Sankhya A 23 (1961) 283–286], have been recently used to construct optimal and efficient designs for many of these experiments. Results in this area are unified and the salient features are outlined.     

Choice of the primary analysis in longitudinal clinical trials

Missing data, and the bias they can cause, are an almost ever‐present concern in clinical trials. The last observation carried forward (LOCF) approach has been frequently utilized to handle missing data in clinical trials, and is often specified in conjunction with analysis of variance (LOCF ANOVA) for the primary analysis. Considerable advances in statistical methodology, and in our ability to implement these methods, have been made in recent years. Likelihood‐based, mixed‐effects model approaches implemented under the missing at random (MAR) framework are now easy to implement, and are commonly used to analyse clinical trial data. Furthermore, such approaches are more robust to the biases from missing data, and provide better control of Type I and Type II errors than LOCF ANOVA. Empirical research and analytic proof have demonstrated that the behaviour of LOCF is uncertain, and in many situations it has not been conservative. Using LOCF as a composite measure of safety, tolerability and efficacy can lead to erroneous conclusions regarding the effectiveness of a drug. This approach also violates the fundamental basis of statistics as it involves testing an outcome that is not a physical parameter of the population, but rather a quantity that can be influenced by investigator behaviour, trial design, etc. Practice should shift away from using LOCF ANOVA as the primary analysis and focus on likelihood‐based, mixed‐effects model approaches developed under the MAR framework, with missing not at random methods used to assess robustness of the primary analysis. Copyright © 2004 John Wiley & Sons, Ltd.