A Bayesian semi-parametric model for learning biomarker trajectories and changepoints in the preclinical phase of Alzheimer's disease.

It has become consensus that mild cognitive impairment (MCI), one of the early symptoms onset of Alzheimer's disease (AD), may appear 10 or more years after the emergence of neuropathological abnormalities. Therefore, understanding the progression of AD biomarkers and uncovering when brain alterations begin in the preclinical stage, while patients are still cognitively normal, are crucial for effective early detection and therapeutic development. In this paper, we develop a Bayesian semiparametric framework that jointly models the longitudinal trajectory of the AD biomarker with a changepoint relative to the occurrence of symptoms onset, which is subject to left truncation and right censoring, in a heterogeneous population. Furthermore, unlike most existing methods assuming that everyone in the considered population will eventually develop the disease, our approach accounts for the possibility that some individuals may never experience MCI or AD, even after a long follow-up time. We evaluate the proposed model through simulation studies and demonstrate its clinical utility by examining an important AD biomarker, ptau181, using a dataset from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) study.

Rationale and design of a multisite randomized clinical trial examining an integrated behavioral treatment for veterans with co-occurring chronic pain and opioid use disorder: The pain and opioids integrated treatment in veterans (POSITIVE) trial.

BACKGROUND: Chronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment. METHODS: A multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms. CONCLUSION: This study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648228.

Bayesian non-parametric survival regression for optimizing precision dosing of intravenous busulfan in allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (allo-SCT) is now part of standard of care for acute leukemia (AL). To reduce toxicity of the pre-transplant conditioning regimen, intravenous busulfan is usually used as a preparative regimen for AL patients undergoing allo-SCT. Systemic busulfan exposure, characterized by the area under the plasma concentration versus time curve (AUC), is strongly associated with clinical outcome. An AUC that is too high is associated with severe toxicities, while an AUC that is too low carries increased risks of disease recurrence and failure to engraft. Consequently, an optimal AUC interval needs to be determined for therapeutic use. To address the possibility that busulfan pharmacokinetics and pharmacodynamics vary significantly with patient characteristics, we propose a tailored approach to determine optimal covariate-specific AUC intervals. To estimate these personalized AUC intervals, we apply a flexible Bayesian nonparametric regression model based on a dependent Dirichlet process and Gaussian process, DDP-GP. Our analyses of a dataset of 151 patients identified optimal therapeutic intervals for AUC that varied substantively with age and whether the patient was in complete remission or had active disease at transplant. Extensive simulations to evaluate the DDP-GP model in similar settings showed that its performance compares favorably to alternative methods. We provide an R package, DDPGPSurv, that implements the DDP-GP model for a broad range of survival regression analyses.

A prior history of substance abuse in veterans undergoing bariatric surgery.

BACKGROUND: The rates of obesity and substance abuse are high among US veterans. OBJECTIVE: To examine weight loss and substance abuse rates following bariatric surgery in veterans with a history of substance abuse (SA). METHODS: A prospective database of consecutive bariatric operations was reviewed. Data for SA patients were compared to patients without a substance abuse history (NA). Behavioral medicine staff followed patients throughout the pre- and postoperative courses. RESULTS: Of 205 bariatric surgery patients, there were 74 (36.1%) SA patients. The mean preoperative body mass index (BMI) was 46.2 ± 8.1 kg/m², and percent excess weight loss at 12 months was 71.8%, 58.0%, and 33.5% for Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic gastric banding, respectively, not significantly different than the NA group (P = 0.15, 0.75, 0.96). Postoperative substance abuse in SA and NA patients was 8.1% and 1.5%, respectively (P = 0.234). CONCLUSION: A prior history of substance abuse is common in veterans undergoing bariatric surgery; weight loss results are comparable to the general veteran bariatric cohort. Rates of substance abuse are low postoperatively, but higher in patients without a prior history of substance abuse. Close multidisciplinary followup throughout the postoperative course is likely to be integral to the patient's success.