Sleep disturbances occur in up to 64 % of hospitalized surgical patients, whilst poor sleep impedes postoperative recovery, e.g. through prolonged immobilization due to fatigue. Common treatment with benzodiazepines, however, is associated with serious side effects, among which an increased risk of cognitive impairment, respiratory depression, agitation, and falls leading to fractures. Music is a potential non-pharmacological treatment option without such adverse events, that has already been proven to reduce pain, anxiety and stress. It is therefore investigated on its effectiveness in improving sleep quality in the perioperative period. We hypothesize that a music intervention is effective in improving perioperative sleep quality.

Obesity is associated with more severe asthma symptoms, more frequent exacerbations, and more frequent asthma-related hospitalisations compared to adults without obesity. Because the origins and expression of obesity varies between individuals, a one-size-fits-all approach to obesity management will not address the underlying cause(s), increasing the risk of treatment failure. We hypothesise that obesity-related asthma is driven by excess adiposity, poor diet quality, physical inactivity, and poor metabolic health, while an individualised obesity management intervention, utilising medical nutrition therapy and personalised physical activity prescription, will result in better asthma control.

Alcohol consumption at unhealthy levels is associated with negative consequences at nearly every step of the HIV care continuum. We describe the rationale, aims, and study design for the ACCEPT Trial, a randomized controlled comparative efficacy trial for Acceptance and Commitment Therapy (ACT) compared to a standard brief alcohol intervention (BI) for people living with HIV (PWH) who drink at unhealthy levels.

The use of tobacco remains a significant health concern among people with HIV (PWH) in India, exacerbating comorbidities, increasing the risk of HIV-related complications and reducing the effectiveness of antiretroviral therapy. This protocol outlines a randomized trial designed to evaluate the effectiveness, cost and implementation of a tobacco cessation intervention for PWH in India.

Healthcare workers and first responders are frequently exposed to traumatic events and subsequently are more susceptible to posttraumatic stress disorder (PTSD), but few receive treatment. Although Employee Assistance Programs (EAPs) are available at almost all large-sized companies, they lack the capacity to provide time-intensive first-line treatments for PTSD. To address this problem, our study team adapted a standard first-line PTSD treatment into a brief, 4-6 session format (Processing Emotions in Primary Care; PE-PC) and demonstrated its efficacy in military and veteran populations. This paper describes a study protocol to leverage the existing resource of the EAP to test intervention effectiveness among healthcare workers and first responders with treatment need.

Posttraumatic Stress Disorder (PTSD) is a debilitating disorder characterized by re-experiencing aspects of the original trauma, avoidance of trauma reminders, negative alterations in cognition and mood, and hyperarousal. Current evidence-based treatments for PTSD have both value and limitations, most notably slow response and high withdrawal rates. The field is searching for more rapid and highly effective interventions. The Stellate Ganglion Block (SGB), which has historically been used to treat regional pain syndromes, causalgia (nerve injury), and intractable angina, has support for being a rapid and highly effective intervention from multiple case series. However, one of two published RCTs was negative and the other had limitations. A larger more definitive study is necessary to provide the evidence needed to determine if SGB is an effective intervention. This paper describes the background, theory and methods of a multi-site triple-blind placebo-controlled trial about the efficacy and safety of the SGB for PTSD. Elements that make this a more definitive study include using and describing a reliably conducted sham, using a standard dose of anesthetic, including an untreated group, rigorously assessing side-effects and safety, and evaluating durability, enhanced dosing, and an objective physiological outcome measure (fear-potentiated startle) to evaluate treatment response in addition to the clinical effect. The strengths and limitations of this research are also presented. CLINICAL TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov ID NCT05169190.

Older adults in medically underserved areas (MUAs) are disproportionately affected by chronic musculoskeletal pain but lack access to safe, evidence-based psychosocial treatments. Staff at community clinics, where many disadvantaged older adults receive care, must manage complex pain needs and comorbidities with limited time and resources. Shared medical visits integrate medical care, education, and peer support, offering a feasible, scalable solution to overcome barriers associated with chronic pain management in primary care. We previously developed GetActive+, an intervention delivered through shared medical visits at a community clinic to teach mind-body and activity skills to older adults with chronic pain. Here, we describe the protocol for a fully powered hybrid type 1 effectiveness-implementation randomized controlled trial (RCT) comparing GetActive+ to treatment as usual (TAU).

Colorectal cancer (CRC) screening rates among patients receiving care at multiple federally qualified health care centers (FQHCs) in New York city are low. Proactive outreach through mailed fecal immunochemical tests (FIT), reminders and navigation are evidence based interventions to improve CRC screening rates but remain untested in this study population.

While there is evidence that vitamin D deficiency is associated with long menstrual cycles, delayed ovulation, and reduced fertility, it is yet unknown if increasing vitamin D levels can regulate menstrual cycles, and thus possibly improve fertility. The primary objective of this randomized clinical trial (RCT) is to test the hypothesis that vitamin D supplementation influences the hypothalamic-pituitary-ovarian axis.

This paper outlines the study protocol for an evaluation of the Let's Connect® (LC) parenting program. LC is a trauma-responsive, emotion-focused parenting program that teaches parents/caregivers to identify and respond to children's emotional needs and behaviors in a way that builds connection and warmth and promotes children's emotional competence, mental and behavioral health, and overall well-being. In a randomized controlled trial (RCT), this project will evaluate the efficacy of LC in a virtual delivery format with families who are at-risk for or have experienced trauma, violence, and/or other adverse life events.

Millions of adults in the U.S. with overweight or obesity would like to improve their health via weight loss, yet utilization of evidence-based weight loss interventions is low. Instead, adults commonly attempt self-guided weight loss, which has poor efficacy. When adults use evidence-based interventions (i.e., behavioral, dietary, commercial, surgical, and pharmacological options), long-term engagement is suboptimal. The proposed project is a pilot randomized clinical trial to test the use of patient navigators to increase uptake of and persistence with evidence-based weight loss interventions. Navigators have been successful in other areas of healthcare to facilitate engagement with various treatment and prevention services. However, little data are available on the feasibility, acceptability, or efficacy of a weight loss navigator program in adults. In the present study, participants (N = 68 adults with a BMI >27 kg/m2 interested in weight loss) will be randomly assigned for a 12-month period to either usual care or the navigator condition. Participants in usual care will have no intervention contact, while participants in the navigator condition will attend individual sessions and receive personalized emails from a navigator to support uptake and persistence with an evidence-based weight loss intervention. Assessments will be conducted remotely at months 0, 6, and 12. The primary outcome for the preliminary test of efficacy is weight change after 12 months. This study will inform future iterations of a weight loss navigator program and could impact clinical practice and public health by enhancing the utilization of evidence-based weight loss interventions.

Effective care for chronic conditions with high rates of non-response or relapse requires personalized and adaptive treatment guidelines known as dynamic treatment regimens (DTRs). Sequential, multiple assignment, randomized trials (SMARTs) are the gold standard for estimating DTRs, but SMARTs, like any trial, may struggle with recruitment and retention due to patient treatment preferences. A partially randomized, patient preference SMART (PRPP-SMART) design overcomes these issues by assigning participants with a preference to their preferred treatment and randomizing indifferent participants at each stage of the SMART. The PRPP-SMART design and methods were motivated in part by STAR*D (NCT00021528), which produced second- and third-line treatment recommendations for patients with major depressive disorder (MDD) who tend to have comorbidities, prior treatment history, and treatment preferences. Traditional, randomized clinical trials typically fail to recruit generalizable study populations, and traditional methods are not appropriate to combine data from randomized and non-randomized participants. We have previously shown that weighted and replicated regression models (WRRMs) combining data from all participants in a PRPP-SMART estimate DTR effects given binary outcomes with minimal bias. Here, we evaluate WRRMs to estimate PRPP-SMART DTRs with continuous outcomes and find that the performance of our method is robust to different preference rates and outcome distributions. We illustrate our method using data adapted from STAR*D which considered preferences in treatment assignment but did not compare DTRs. The PRPP-SMART design and methods presented here would have overcome many shortcomings of STAR*D and establish a framework for meaningful DTR estimates in future pragmatic SMARTs.

Antiphospholipid syndrome (APS) is closely associated with ischemic stroke. However, optimal treatment for APS-related stroke remains unestablished, as current guidelines are based on outdated studies and expert opinion rather than high-quality clinical trials. Evidence on antiplatelet agents other than aspirin, such as clopidogrel, in APS-related stroke is particularly limited. Given the relatively young age of patients with APS and the burden of warfarin use, verifying its necessity is crucial. This study compares clopidogrel-based antiplatelet therapy and warfarin for secondary prevention in APS-related stroke.

Black women in the U.S. disproportionately suffer from insomnia and related cardiometabolic health burdens. However, there is a lack of sleep intervention and implementation research specifically targeting Black women. The aim of this study is to co-design and evaluate equity-focused, community-engaged implementation strategies for an online, group-based mindfulness-based therapy for insomnia (MBTI) tailored for Black women, and to test the effectiveness of MBTI. The study will utilize trained registered nurses to deliver the online MBTI sessions and integrate community health workers (CHWs) to address social determinants of health. This two-phase, study includes: (1) qualitative individual interviews with Black women, CHWs, and clinicians to identify barriers/facilitators to online MBTI (N = 10-40) (2) the development of equity-focused implementation strategies through community engagement process with the Community Advisory Board (clinicians, CHWs, social workers, and community-based organization members), and (3) a Hybrid Type 1 randomized controlled trial comparing online group-based MBTI to a waitlist control (N = 340). Implementation outcomes include acceptability (mean summary score ≥ 3.5 out of 5-point Likert scale), feasibility (≥ 80 %), fidelity (≥ 85 %), cost, and contextual factors; effectiveness outcomes include changes in Insomnia Severity Index scores (≥ 7-point reduction post-intervention) and actigraphy-measured sleep (an increase in total sleep time 20-40 min post-intervention). This study addresses the urgent need for equity-focused intervention and implementation research in sleep health. The study will evaluate how tailoring evidence-based interventions to community needs, leveraging CHWs, and embedding community partnership throughout the process improves access, uptake, and outcomes in Black women with insomnia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06348082.

Fatigue's interference with activities, mood, and cognition is one of the most prevalent and distressing problems of patients with advanced gastrointestinal cancer. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing demands. Evidence-based interventions for patient fatigue interference and caregiver burden are lacking in advanced gastrointestinal cancer. In a pilot trial, telephone-based Acceptance and Commitment Therapy (ACT) showed potential for reducing patient fatigue interference and caregiver burden in this population. The current Phase II trial seeks to determine the efficacy of this intervention for patients with advanced gastrointestinal cancer and moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden. In this trial, 244 dyads are randomly assigned to either the ACT intervention or an education/support control. Participants in both conditions attend six weekly 50-min telephone sessions, four of which involve both dyad members, and a 30-min booster session. The primary aim is to test the effects of telephone-delivered ACT on patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities and quality of life. Outcomes are assessed at baseline, 2 weeks post-intervention, and 3 months post-intervention. This trial also examines whether increased psychological flexibility, defined as mindful acceptance of present experiences, including challenges, while pursuing actions aligned with personal values, mediates ACT's effects on primary outcomes. Our ability to demonstrate ACT's efficacy will support its adoption in cancer care. Findings will also inform future ACT trials for dyads coping with other serious illnesses. Trial Registration ID: NCT06532877.

Prevention of alcohol use and misuse among adolescents is a public health priority. A health care visit provides an opportunity for screening for alcohol use and delivery of early interventions. Digital intervention delivery may reduce barriers to implementation in these settings. Herein, we describe the protocol from an ongoing comparative effectiveness study testing digital interventions to prevent escalation of alcohol use among adolescents (ages 12-19) connected to pediatric healthcare. Adolescents screening positive for past-year alcohol use are eligible to participate. Enrolled participants complete a baseline survey and are randomly assigned [stratified by sex and age group (12-14; 15-17; 18-19)] to an interactive, ∼45-min computerized brief intervention (CBI) alone or combined with 8 weeks of text messages. Outcomes are assessed at 3-, 6-, 9-, and 12-months post-baseline. Primary outcomes include past 3-month alcohol consumption. Secondary outcomes include alcohol and drug consequences, illicit and prescription drug misuse, and depression symptoms. In parallel, caregivers are also invited to participate, which involves referral to download the app "Talk. They Hear You." and completing surveys at baseline, 3-, 6-, 9- and 12- months to report their use of the app. A novel aspect of this study is that we partnered with adolescents, caregivers, and health care staff and clinicians throughout the study to enhance relevance, effectiveness, and potential for future dissemination. This study will provide critical data to inform implementation of digital interventions for pediatric patients with the potential to prevent negative health outcomes and promote adolescent well-being.

Diet and exercise are the cornerstone of obesity prevention and treatment. However, a substantial number of individuals are non-responsive to existing weight-loss interventions and obesity rates continue to rise. Daily exposure to low-oxygen conditions may aid in current weight-loss strategies by increasing resting metabolic rate and decreasing appetite. Whether in-home, overnight, normobaric hypoxic exposure promotes body weight loss in adults with obesity remains unknown.

Monetary interventions, such as cash transfers, have emerged as important intervention approaches to address the complex determinants at the structural and individual level impacting diabetes outcomes.

The Enhanced Quality in Primary Care for Elders with Diabetes-ADRD (EQUIPED-ADRD) is a quality improvement and pragmatic cluster-randomized controlled trial that uses clinical decision guidelines to streamline the care of older adults with diabetes mellitus and Alzheimer's disease/Alzheimer's disease-related Dementia (DM-AD/ADRD). This study tests whether the EQUIPED-ADRD intervention will increase the proportion of older adults with DM and AD/ADRD with desirable glycemic ranges, and reduce treatment burden, dementia severity, and healthcare utilization among participants and their care partners in the intervention arm compared to those in the control arm.

Decentralized Clinical Trials (DCTs) represent a significant advancement in clinical research, offering greater accessibility, flexibility, and participant engagement through the use of telemedicine, mobile health technologies, and remote data capture. However, the decentralized nature of data collection introduces challenges related to data reliability and variability, which are often inadequately addressed by conventional statistical methods at the design stage of the trial. This study presents an agile Bayesian design framework tailored to the specific needs of DCTs, integrating adaptive data reliability directly into trial design and analysis. Our approach is based on Bayesian decision rules to guide interim sample size adjustments. By treating data reliability as a model parameter rather than an external factor, our method accounts for uncertainty and improves the robustness of power calculations. Simulation studies demonstrate the effectiveness of this strategy. The proposed framework enables a flexible and agile approach to DCT design that can adapt to varying data quality conditions. This work offers a foundation for extending the proposed adaptive method to other trial contexts, including time-to-event endpoints, and supports the broader adoption of DCTs in real-world clinical research.

Atrial fibrillation (AF), heart failure (HF), and undernutrition represent a complex triad with major clinical and socioeconomic consequences in older adults, often predisposing to frailty. Undernutrition often remains underdiagnosed due to a reliance on weight-based measures and limited awareness of inflammation-related cachexia. The AMBROSIA study aims to fill these gaps by exploring the response of the microbiota-inflammation-brain axis to a targeted, fortified food product-based intervention, with comprehensive outcome assessments, alongside mechanistic/exploratory -omics analyses and gut microbiota (GM) functional profiling.