Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

A comparison of a pseudo-likelihood estimation and full information maximum likelihood estimation for fitting multivariate longitudinal ordinal data

We consider a latent variable model for multivariate ordinal responses accounting for dependencies among items. Time-dependent latent variables and random effects account for the inter-dependencies of the multivariate ordinal items. Model estimation is usually obtained using the full maximum likelihood via the EM algorithm. However, computationally problems can arise due to the calculation of multiple integrals involved in the likelihood. The paper proposes a pseudolikelihood approach which involves only bivariate marginal probabilities. The proposed estimation method is evaluated by means of a little simulation study. A real data example illustrates the performance of both the full and the limited information estimation method

A novel reversible jump algorithm for generalized linear models

We propose a novel methodology to construct proposal densities in reversible jump algorithms that obtain samples from parameter subspaces of competing generalized linear models with differing dimensions. The derived proposal densities are not restricted to moves between nested models and are applicable even to models that share no common parameters. We illustrate our methodology on competing logistic regression and log-linear graphical models, demonstrating how our suggested proposal densities, together with the resulting freedom to propose moves between any models, improve the performance of the reversible jump algorithm. Copyright 2011, Oxford University Press.

Nonparametric estimation of individual food availability along with bootstrap confidence intervals in household budget surveys

An additive nonparametric model is proposed for the analysis of household budget surveys data whose estimation reduces to least squares. Parameter estimates are biased. A first-order approximation for the bias is obtained and it is used to bias correct the residuals of the model in order to construct bootstrap confidence intervals for the model parameter estimates. The results show somewhat shorter intervals than pointwise intervals which are based on a normal approximation with less bias.Nonparametric models Least squares Bias Bootstrap confidence intervals

A modified weighted pairwise likelihood estimator for a class of random effects models

Composite likelihood estimation has been proposed in the literature for handling intractable likelihoods. In particular, pairwise likelihood estimation has been recently proposed to estimate models with latent variables and random effects that involve high dimensional integrals. Pairwise estimators are asymptotically consistent and normally distributed but not the most efficient among consistent estimators. Vasdekis et al. (Biostatistics 15:677-689, 2014) proposed a weighted estimator that is found to be more efficient than the unweighted pairwise estimator produced by separate maximizations of pairwise likelihoods. In this paper, we propose a modification to that weighted estimator that leads to simpler computations and study its performance through simulations and a real application

Detection of gingival crevicular fluid cytokines in children and adolescents with and without fixed orthodontic appliances

Objective. To study the expression of IL-1β, IL-4, and IL-8 in the gingival crevicular fluid (GCF) of children, adolescents, and young adults with and without fixed orthodontic appliances. Material and methods. Eighty systemically healthy children and adolescents participated in the study: 56 aged between 8 and 16 years without any orthodontic appliance (Group A) and 24 aged between 10 and 20 years having worn fixed orthodontic appliances for at least 12 months (Group B). Clinical examination included presence or absence of plaque, probing depth, bleeding on probing, and gingival overgrowth. GCF was collected by means of Durapore strips from four randomly selected sites per subject. The contents of interleukin-1 beta (IL-1β), interleukin-4 (IL-4), and interleukin-8 (IL-8) were detected by ELISA, measured as total amounts (pg/30s) and expressed in log scale. Results. Statistically significant differences were noted for the mean log IL-1β, IL-4, and IL-8 between the two groups: Group B showed significantly higher mean levels in log IL-1β and log IL-8 compared to Group A. Mean levels of log IL-4 were lower in Group B, although they did not reach statistical significance. Furthermore, mean levels of log IL-1β and log IL-8 were associated with bleeding sites (p<0.001) and gingival overgrowth, while mean level of log IL-4 was associated with non-bleeding sites and no gingival overgrowth (p<0.001). Conclusion. Our findings suggest that fixed orthodontic appliances result in an increase in the expression of IL-1β and IL-8. This may reflect biologic activity in the periodontium during orthodontic tooth movement. © 2008 Taylor & Francis

Prognostic significance of flow cytometry MRD log reduction during induction treatment of childhood ALL

[No abstract available

Brain-derived neurotrophic factor (BDNF) in children with ASD and their parents: a 3-year follow-up

Objective: Several lines of evidence point to a probable relationship between brain-derived neurotrophic factor (BDNF) and autism spectrum disorder (ASD), but studies have yielded inconsistent findings on the BDNF serum level in ASD. The study aimed to assess those levels in children with ASD and their families. Method: BDNF serum levels were measured in 45 ASD children without intellectual disability (ID) and allergies, age 30–42 months and age-matched normal controls. BDNF serum levels in the parents of the ASD subjects were compared to normal controls. BDNF serum levels in the ASD subjects were followed up for 3 years and correlated with adaptive functioning changes. Results: BDNF serum levels were measured to be lower in children with ASD and independent of all the major baseline characteristics of the subjects. Having a child with ASD raises the BDNF levels in parents comparing to controls. Prospectively, no correlation between the change of BDNF variables in time and the change of the Vineland scores was found. Conclusions: Our results contradict those from recent published meta-analyses with the age, the presence of ID and allergies being possible contributing factors. The parents’ data indeed point to a role of BDNF in the pathophysiology of ASD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

Neuroendocrine System Adaptation during Consecutive Extrinsic Stimuli: A Pilot Dynamic Study

This pilot repeated measures study aims to evaluate the dynamics of the autonomic nervous system (ANS), the hypothalamic–pituitary–adrenal (HPA) axis, and/or their interplay with low-level inflammation in healthy schoolchildren during consecutive extrinsic stimuli. Twenty healthy schoolchildren and adolescents aged 11–14 years (12.5 ± 1.5) were consecutively exposed to an oral task (#2) and an arithmetic task (#3) (Trier Social Stress Test for Children (TSST-C)), lasting 5 min each, and a three-minute cellular phone call (#4). Salivary cortisol (SC) was sampled at baseline (#1) and immediately after each exposure (#2, 3, and 4). Baseline serum high-sensitivity C-reactive protein (hsCRP) and cortisol levels were also assessed. ANS dynamics and complexity were measured using Sample Entropy (SampEn) at each experimental time period (#1–4). Baseline serum hCRP and cortisol correlated negatively to each other, while the ANS and HPA axis acute reactions to the three consecutive stimuli differed over time. The ANS adaptation to these stimuli included complexity modulation, which was not dependent on baseline hsCRP or cortisol, and weakened during the third stimulation. However, baseline hsCRP and cortisol had a weakening and an increasing effect on the HPA axis over time, respectively. We conclude that low-level inflammation and baseline morning cortisol level have no effect on ANS dynamics but influence the HPA axis response to consecutive external stimuli