Longitudinal study of adolescent stress, critical consciousness and resilience trajectories in the context of structural racism: the RISE Baltimore study protocol

Introduction
Systemic racism exposes Black and Latinx adolescents to a range of traumatic stressors that increase the risk for long-term emotional and behavioural health (EBH) problems. Researchers have theorised that critical consciousness (CC)—awareness of societal inequities and engagement in action to promote social justice—may serve as a protective factor that promotes youth well-being. There are few rigorous longitudinal research studies, however, that examine the development of CC among adolescents, the association over time of CC with EBH and the potential of CC to protect against harmful effects of race-related stress. This longitudinal study, Resilience in a Stressful Era (RISE), addresses these gaps using a mixed methods approach with Black, Latinx and White adolescents in Baltimore.

Methods and analysis
We plan to enrol up to 650 Black, Latinx and White adolescents ages 14–19 who reside in Baltimore, Maryland. The recruitment will include outreach through youth-serving organisations, community events, youth networks, social media, snowball sampling and re-contacting adolescents who participated in a prior study (R01HD090022; PI: Mendelson). Participants will complete online questionnaires assessing exposure to pandemic- and race-related stress, CC and EBH twice per year over 4 years as they transition into early adulthood. Using an explanatory sequential mixed methods approach, in-depth interviews exploring the development and impact of CC will be conducted with a subset of participants selected based on their CC scores and, separately, their caregivers. A Youth Advisory Board comprised of adolescents who are representative of our target study population will be developed to provide input on the study and its implementation. Growth mixture modelling and latent variable modelling will be used to analyse quantitative data. Themes identified through qualitative analyses will expand the understanding of quantitative findings.

Ethics and dissemination
All study procedures were approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board. Findings will be disseminated through publications in peer-reviewed journals and presentations at academic conferences. We will also communicate research findings with study participants and disseminate findings to the Baltimore community, such as developing briefs for the Baltimore City Health Department and/or hosting a town hall meeting for Baltimore families.

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Maggio 2025

Cost-effectiveness of massed versus spaced trauma-focused treatment as first-line treatment for post-traumatic stress disorder in adults with multiple trauma exposure: protocol for a single-blind non-inferiority randomised controlled trial

Introduction
Post-traumatic stress disorder (PTSD) is a serious disorder that burdens individuals and society. The current standard of first-line treatment for PTSD is spaced trauma-focused treatment (S-TFT), involving weekly sessions. While effective, S-TFT may take relatively long to complete, especially in patients exposed to multiple potentially traumatic events (PTEs). Massed trauma-focused treatment (M-TFT), involving increased session frequency, potentially results in faster symptom reduction and restoration of quality of life, as well as in a reduction of societal costs. However, M-TFT is not recommended as first-line treatment. This paper describes the research protocol of a single-blind, multicentre randomised controlled trial (RCT) aimed at investigating: (1) the clinical and cost-effectiveness of M-TFT versus S-TFT in employed, multiply traumatised patients who seek first-line treatment for PTSD and (2) predictive and moderating factors related to treatment response.

Methods and analysis
186 participants are recruited from five centres and will be included if they are ≥18 years old, meet criteria for a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition PTSD diagnosis based on ≥two PTEs, seek treatment for the first time and are employed. Patients with specified comorbid disorders and insufficient Dutch language proficiency are excluded. Participants are randomised to 800 min of either M-TFT or S-TFT. M-TFT consists of two once-weekly preparatory sessions, 10 twice-daily sessions of prolonged exposure, eye movement desensitisation and reprocessing therapy for 2 weeks and two once-weekly closing sessions. S-TFT consists of weekly sessions of one of five evidence-based treatment interventions. Outcomes are assessed at baseline and at 7 weeks, 17 weeks, 6 months and 9 months after baseline. Primary outcomes are clinical effectiveness in terms of PTSD symptom severity and cost-effectiveness based on quality of life measures and societal costs. Data will be analysed with linear mixed models.

Ethics and dissemination
This study protocol was approved by the Medical Ethics Review Board of the Amsterdam University Medical Center (NL86057.018.24). Participants will provide informed consent before enrolment in the trial. Results will be published in peer-reviewed journals and will be released to clinicians, patient groups and the general community.

Trial registration number
This protocol is registered at Overview of Medical Research in the Netherlands (OMON; trial register number 56960) and ClinicalTrials.gov (NCT06700590).

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Maggio 2025

Assessment of the prevalence of stress, anxiety and depression in healthcare workers providing services related to communicable diseases in primary-level health units in Maputo city, Mozambique: an observational cross-sectional study protocol

Introduction
Mental health is essential for well-being and critical to the quality of care delivered by healthcare professionals. Health workers face increased risks of mental health disorders due to long hours, high emotional and physical demands, and exposure to communicable diseases, which exacerbate stress and anxiety levels. Evidence from low-income countries, including Mozambique, is scarce, yet health professionals in these regions frequently deal with the dual burden of communicable diseases and resource constraints. This study addresses a critical evidence gap by focusing on the mental health of healthcare professionals in Mozambique who are frequently exposed to psychological stress while managing communicable diseases. It aims to assess the prevalence of stress, anxiety and depression among healthcare workers providing services related to communicable diseases in primary-level health units (PHUs) in Maputo City, Mozambique. The study also seeks to identify personal and professional factors associated with these mental health disorders.

Methods and analysis
This is an observational cross-sectional study targeting healthcare workers in PHUs who provide services related to communicable diseases in Maputo City. Using convenience sampling, 382 participants will be recruited, stratified by health unit type. This sample size was calculated manually using the formula by Wang and Ji (2020). Data will be collected through a questionnaire, including demographic and professional information and a validated tool (Depression, Anxiety and Stress Scale, DASS-21), using the Research Electronic Data Capture (REDCap) Software for secure data capture. Descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics to estimate prevalence rates and explore associated factors.

Ethics and dissemination
The study was approved by the Interinstitutional Committee on Bioethics in Health of the Faculty of Medicine/Maputo Central Hospital (CIBS FM&HCM/117/2024). Written informed consent will be obtained, and participants experiencing significant discomfort will be referred for mental health support. Findings will be disseminated via academic theses, peer-reviewed publications, national conferences, and reports shared with the Ministry of Health to inform mental health interventions for healthcare workers.

Registration
This protocol is registered with the Interinstitutional Committee on Bioethics in Health of the Faculty of Medicine/Maputo Central Hospital (CIBS FM&HCM).

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Maggio 2025

Augmentation of trauma-focused psychotherapy for post-traumatic stress disorder: a protocol for a systematic review and meta-analysis

Introduction
Despite the established status of trauma-focused psychotherapy (TFP) as a first-line treatment for post-traumatic stress disorder (PTSD), a substantial proportion of individuals do not achieve clinically significant improvement or discontinue treatment. Exploring augmentation strategies to enhance treatment outcomes is essential to reduce the overall burden PTSD puts on individuals and society. This protocol outlines a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the efficacy of non-pharmacological augmentation strategies in addition to TFP for PTSD treatment.

Methods and Analysis
We comprehensively searched PubMed, Embase, CENTRAL, PTSDpubs, PsycArticles, PsycINFO, PSYNDEX and CINAHL for RCTs without restrictions on publication dates or languages in October 2024. Study screening is currently ongoing. Additionally, we will perform forward and backward searches of the included studies and relevant reviews. Two reviewers will independently screen and select studies, extract data and assess the risk of bias. We will conduct a narrative review to qualitatively synthesise data and a meta-analysis to quantitatively compare the treatment efficacy of augmented TFP with TFP alone or TFP plus placebo. Primary outcomes will be both symptom severity and response rates. The secondary outcome will be dropout rates. We will explore sources of between-study heterogeneity and potential moderators through subgroup and meta-regression analyses. We will assess the overall quality of the included studies with the Grading of Recommendations Assessment, Development, and Evaluation system.

Ethics and dissemination
Ethical approval is not required. We intend to publish results in a peer-reviewed journal and provide materials and data through the Open Science Framework.

PROSPERO registration number
CRD42024549435.

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Maggio 2025

Outcomes of participating in the Lets Play programme on 0-5-year-old autistic childrens engagement and caregivers stress: study protocol for a parallel randomised controlled trial

Introduction
Vast empirical evidence highlights the importance of early identification, diagnosis and support for autistic children. Caregivers of autistic children often experience high levels of psychological distress; hence there is a need for parallel child and caregiver support. Autism New Zealand’s Let’s Play programme is a caregiver-mediated, community-based programme based on the principles of developmental and relational interventions (henceforth, developmental). Developmental interventions are evidence-based supports designed to enhance children’s learning within the context of developmentally appropriate, naturalistic settings (eg, everyday routines, play). We aim to evaluate the effects of the Let’s Play programme on autistic children’s engagement and caregiver stress.

Methods and analysis
This study will be a single-blind (rater) randomised controlled trial with two parallel arms: immediate programme access (intervention) versus a waitlist control. Participants will be 64 caregivers of children aged 0–5 years with diagnosed or suspected autism, allowing for 20% attrition, based on power calculations. The Let’s Play programme will be delivered over 9 weeks using a combination of small group workshops and in-home coaching. Primary outcome variables include child engagement and caregiver stress. Caregivers will complete measures at three time points (baseline, immediately post-programme and at the 6-month follow-up), and effectiveness will be analysed using generalised estimating equation models and intention-to-treat and per protocol analyses.

Ethics and dissemination
This trial was approved by Aotearoa New Zealand Ministry of Health’s Health and Disability Ethics Committee (2022 FULL 13041). Findings will be communicated nationally and internationally via conferences, journal publications and stakeholder groups (eg, service providers for autistic children). Results will be shared regardless of magnitude or direction of effect.

Trial registration number
ACTRN12622001139763.

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Maggio 2025

Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8+ T cell exhaustion

Background
Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.

Objective
We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8+ T cells.

Design
4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.

Results
Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8+ T cells, thereby promoting HNSCC tumourigenesis.

Conclusion
CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8+ T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.

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Maggio 2025