Nonlinear mixed-effects models for HIV viral load trajectories before and after antiretroviral therapy interruption, incorporating left censoring.

Objectives: Characterizing features of the viral rebound trajectories and identifying host, virological, and immunological factors that are predictive of the viral rebound trajectories are central to HIV cure research. We investigate if key features of HIV viral decay and CD4 trajectories during antiretroviral therapy (ART) are associated with characteristics of HIV viral rebound following ART interruption. Methods: Nonlinear mixed effect (NLME) models are used to model viral load trajectories before and following ART interruption, incorporating left censoring due to lower detection limits of viral load assays. A stochastic approximation EM (SAEM) algorithm is used for parameter estimation and inference. To circumvent the computational intensity associated with maximizing the joint likelihood, we propose an easy-to-implement three-step method. Results: We evaluate the performance of the proposed method through simulation studies and apply it to data from the Zurich Primary HIV Infection Study. We find that some key features of viral load during ART (e.g., viral decay rate) are significantly associated with important characteristics of viral rebound following ART interruption (e.g., viral set point). Conclusions: The proposed three-step method works well. We have shown that key features of viral decay during ART may be associated with important features of viral rebound following ART interruption.

A patient-oriented analysis of pain side effect: A step to improve the patient's experience during rTMS?

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an efficacious and well-tolerated intervention for treatment-resistant depression (TRD). A novel rTMS protocol, intermittent theta burst stimulation (iTBS) has been recently implemented in clinical practice, and it is essential to characterize the factors associated to pain and the trajectory of pain of iTBS compared to standard rTMS protocols. OBJECTIVE: We aimed to characterize the side effect profile and the pain trajectories of High-Frequency Left (HFL) and iTBS in TRD patients in the THREE-D trial. We also investigated factors associated to pain and the relationship between pain and clinical outcomes. METHODS: 414 patients were randomized to either HFL or iTBS. Severity of pain was measured after every treatment. General Estimating Equation was used to investigate factors associated with pain. Latent class linear mixed model was used to investigate latent classes of pain trajectories over the course of rTMS. RESULTS: Higher level of pain was associated with older age, higher stimulation intensity, higher anxiety, female, and non-response. The severity of pain significantly declined over the course of treatments with a steeper decrease early on in the course of the treatment in both protocols, and four latent pain trajectories were identified. The less favorable pain trajectories were associated with non-response and higher stimulation intensity. CONCLUSIONS: HFL and iTBS were associated with similar factors and pain trajectories, although iTBS was more uncomfortable. Response to rTMS was associated with less pain and more favorable pain trajectories furthering the evince base of overlapping neurobiological underpinnings of mood and pain. We translated these results into patient-oriented information to aid in the decision-making process when considering rTMS.

Effect of combined yoga and transcranial direct current stimulation intervention on working memory and mindfulness.

Transcranial direct stimulation, a non-invasive neurostimulation technique for modulating cortical excitability, and yoga have both respectively been shown to positively affect cognition. While preliminary research has shown that combined transcranial direct stimulation and meditation may have synergistic effects on mood and cognition, this was the first study to explore the combination of transcranial direct stimulation and yoga. Twenty-two healthy volunteers with a regular yoga practice were randomized to receive either active transcranial direct stimulation (anodal left, cathodal right dorsolateral prefrontal cortex) followed by yoga intervention or sham transcranial direct stimulation followed by yoga intervention a double-blind, cross-over design over two separate intervention days. Outcome measures included working memory performance, measured with the n-back task and mindfulness state, measured with the Toronto Mindfulness Scale, and were conducted offline, with pre-post assessments. Twenty participants completed both days of the intervention. Active transcranial direct stimulation did not have a significant effect on working memory or levels of mindfulness. There was a significant placebo effect, with better performance on day 1 of the intervention, irrespective of whether participants received active or sham transcranial direct stimulation. There was no significant difference between active versus sham transcranial direct stimulation concerning working memory performance and mindfulness, which may be accounted by the small sample size, the transient nature of the intervention, the fact that yoga and transcranial direct stimulation concerning were not conducted simultaneously, and the specific site of stimulation.