Cognitive Behavioral Therapy (CBT)

Reactions to severe stress is one of the most common causes of sick leave in Sweden. Previous research has shown that compassion interventions for staff can affect work-related stress by increased self-care, better self-awareness and an increased healthy attitude, however, Swedish studies on the subject are scarce. Compassion is a motivation to reduce suffering in oneself and others characterized by a warm, understanding, and respectful attitude. In addition to beneficial effects for the staff, a compassion-oriented approach, has shown to improve the relationship between patient and staff, increase patient satisfaction with care and reduce patient anxiety and stress. As a result of the covid-19 pandemic, healthcare professionals have been exposed to difficult physical and mental work conditions that cause feelings of stress and inadequacy. In the long run, increased stress can cause fatigue and increased number of sick leaves. This can in turn contribute to increased stress for the staff who remain working and difficulties to recruit new staff, which make the situation worse. There is a lack of interventions for staff aimed at preventing stress-related health issues, enabling recovery and reduce mental suffering linked to a stressful work situations. The aim of this study is to find a method that help healthcare providers cope with stress of conscience in relation to stressful work situations, particularly during the current covid-19 pandemic. A five week internet-based compassion course of five modules will be conducted and evaluated with the aim of exploring whether the course contributes to reduce stress of conscience and work-related stress, and increases the levels of professional quality of life and self-compassion among healthcare professionals. The internet-based compassion course will be compared with: one group that is on a waiting list for ten weeks and then receives an internet-based general stress management course and one group that participate in the general stress management course.

Complex posttraumatic stress disorder (cPTSD) is characterized by chronic and pervasive disruptions in emotion regulation, identity, and relationships following prolonged or multiple exposures to trauma. It is frequently found in patients with addiction. Individuals with cPTSD have more severe addiction. In addition, the co-occurrence of these two disorders is often associated with certain transdiagnostic processes such as impulsivity. Indeed, PTSD is linked to a higher impulsivity score, which in turn promotes increased substance use. A second process also associated with trauma and addiction is hostile attribution bias. Thus, the trauma-addiction comorbidity generates multiple behavioral consequences (aggression, increased substance use, etc.) that impact patients' quality of life and represent an important treatment target. Many authors and clinicians have worked on creating treatment programs targeting both disorders, although group format treatment lacks empirical support. Indeed, even though the Seeking Safety program has been shown to be effective in reducing PTSD symptoms and substance use, there is currently no evidence to suggest its superiority. The ECCCLORE program is a new 6-month cognitive behavioral therapy protocol initially designed for patients with borderline personality disorder, in whom addictive and traumatic issues are common. It is shorter than the standard dialectical behavioral therapy (DBT) program, which focuses on emotional dysregulation, impulsivity, and the traumatic dimension and lasts at least 1 year. It also integrates techniques from other approaches such as Acceptance and Commitment Therapy (ACT), which promotes the acceptance of internal experiences and engagement in actions consistent with values. It notably contains tools for developing emotional, distress tolerance, and interpersonal skills that could adapt to the difficulties generated by trauma and addiction. The objective of this research is to test the feasibility and acceptability of a 12-week ECCCLORE program adapted for patients with addictive and traumatic problems. The study investigators hypothesize that the implementation of this program will demonstrate satisfactory feasibility and acceptability.

Pilot Study: 36 parents will be recruited to participate in the study. Additionally, 3 therapists with extensive online support group experience to conduct the Parent-FORT videoconference therapy sessions. Therapist competency to administer Parent-FORT will be determined by registered professionals in counselling or psychotherapy, experience in psychosocial oncology, specifically with parents, and having led at least one group. Interested parents will contact the research coordinator, via telephone or email, to be screened for eligibility and to complete the consent forms. This pilot study will serve as a first step in potential sample size calculations and recruitment times. For this pilot study, active recruitment will last for a period of 15 months during which 36 parents are aimed to be recruited in order to create 4 groups of 9 participants (2 intervention conditions and 2 WLCG). Feasibility of recruitment for the larger RCT will be determined using these criteria: 1) If during our recruitment period less than 18 participants, recruitment for a larger RCT, using our current recruitment strategies, will be deemed not feasible, 2) If between 18 and 25 participants are recruited, then a larger multicentre approach for recruitment will be considered, 3) If recruit 25 participants or more, recruitment for a larger RCT, using our current methods, will be deemed feasible. The sample size will be reevaluated for the larger RCT based on the results from this pilot study. Parent-FORT consists of 7 consecutive weekly group sessions of 120 minutes each offered through videoconference and weekly assigned homework. Parent-FORT is therapist led, however participants will receive a workbook where they can follow along, take notes, and complete the exercises and the homework assignments. The overall aim of Parent-FORT is to guide Parent towards a more manageable level of worry and fear of recurrence. The key goals are to: 1) distinguish worrisome symptoms from benign ones; 2) identify FCR triggers and inappropriate coping strategies; 3) facilitate the learning and use of new coping strategies, such as relaxation techniques, cognitive restructuring, communication strategies and the use of self-care; 4) increase tolerance for uncertainty; 5) promote emotional expression of specific fears that underlie FCR; and 6) re-examine life priorities and set realistic goals for the future. Each session is composed of exercises where participants have to answer questions, share with the group or watch videos. Furthermore, homework is assigned after each session to be completed before next week's session. Eligible participants will attend a one-on-one pre-therapy meeting with a study therapist to prepare them for the group work (i.e.: review expectations and assess whether group work is appropriate for the participant) and complete the 7-week Parent-FORT intervention. Membership will be closed once groups are formed and the sessions have started to enhance group cohesiveness and consistency. Before starting the intervention, participants will receive a standardized manual describing each session's activities and assignments. All participants (including those in the wait list control group) will complete a questionnaire package pre intervention, post intervention, and at a three month follow up via Qualtrics. Additionally, participants will be asked to complete post session measures, namely the Working Alliance Inventory - Revised Short Form as well as the Group Cohesiveness Scale after the 1st, 4th and 7th sessions. Therapist Training and Supervision: To enhance therapist adherence to treatment, the therapists recruited for the study will be provided with a standardized Parent-FORT manual and will be trained by the research psychologists through an online training. The research team will review the video of each session, and the principal investigator will provide weekly 30-minute supervision to the therapists. Furthermore, the study will use an updated version of the fidelity checklist that was used to evaluate adherence during the previous FORT studies. If adherence is less than 80% on any session, the research team will provide additional over-the-telephone feedback to the therapists running the group. This approach to monitoring treatment integrity and fidelity has been successful in previous FORT studies. Qualitative Assessment: To gain further insights about the feasibility, acceptability, and potential clinical significance of Parent-FORT, all study participants will be asked to complete semi-structured exit interviews. This will enable a holistic understanding of their experience of Parent-FORT, elucidate key intervention processes, and identify additional secondary outcomes. Lastly, the research coordinator will attempt to interview participants who dropped out of the intervention, to understand any hindering factors. Consenting participants will be asked to complete a semi structured interview (30-60 minutes) about their experience of the intervention through videoconferencing. Randomization: This study will use a mixed method randomized control trial design using a waitlist control group and 3 months follow up, with 18 participants per condition. To minimize attrition associated with waiting to enroll participants, block randomization will be used. Specifically, a list of 4 blocks with equal numbers of intervention (I) and wait list control (WLCG) groups (e.g. I-I-WLCG-WLCG; I-WLCG-WLCG-I, etc.) will be randomly created. Once the first 9 participants have been recruited, they will be assigned to whichever group came up first on the list. The next 9 participants will be assigned to the next group on the generated list until all 4 groups have been completed. Participants assigned to the WLCG will be offered the intervention after the 3-month period. To limit bias, each of the 4 blocks of the list will be in separate sealed envelopes that will be opened one at a time after 9 participants have been recruited. Minimizing Dropouts and Attrition: To maximize attendance, as in our prior research, participants will be told during informed consent procedures about the importance of attending all 7 sessions to ensure benefit from the intervention. Participants will receive two email reminders about each upcoming session, along with "homework" and session pre-reading materials. They will be asked to inform group therapists if they are to be absent. For participants who miss a session, they will be offered one individual videoconference make-up session for their first missed session before the next group; they will not be offered subsequent make-up sessions for additional missed sessions to decrease the risk that this would encourage those who prefer individualized attention to miss group sessions. Participants who miss more than two sessions will be asked to stop the intervention and restart with the next available group. This approach was successfully tested in previous FORT studies. To minimize differential attrition from the WLCG participants, participants will be emailed monthly with an update about the wait time. Feasibility and Acceptability Criteria: The following criteria will be used to assess the feasibility and acceptability of Parent-FORT: 1) ability to recruit 36 parents in 15 months; 2) ability to randomize these 36 parents; 3) ability to deliver Parent-FORT to 27 Parent in 15 months (25% dropout rate); 4) 80% completion of 6 out of the 7 sessions; 5) complete measures for 90% of participants; 6) ability to deliver Parent-FORT as intended as measured by a fidelity rating of above 80% on 75% of reviewed sessions; and 7) Parent satisfactory ratings \>than 80% in terms of its content, therapists, and mode of delivery. Quantitative analysis: Descriptive statistics will be used to report on FCR outcomes. A linear mixed-effect model analyses will be done on the secondary outcome measures pre- and post-intervention and at the 3-month follow-up. All analyses will use both an intent-to-treat and per protocol approaches. Known extraneous variables that could influence FCR (e.g., age, education, income, cancer stage) will be measured and control for, and monitor for participants' use of any additional psychological support at each data-collection time-points. Dependence of the group data will be analyzed with an intraclass correlation coefficient (p) using a multilevel model. Qualitative Analysis: Conventional content analysis will be used to analyse the qualitative data. Interviews will be audiotaped, transcribed verbatim, and managed using the qualitative software program NVivo. Transcripts will be systematically coded into anticipated (e.g., motivations to participate, benefits of participation) and emergent codes. This is an iterative process whereby an initial set of themes are coded, applied to new transcripts, and revised to adjust for new information, until no new codes emerge. Double coding of 80% of the interviews will be done by the research assistant. These codes will then be sorted into subcategories (ideally between 10 to 15).

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that poses substantial challenges for both families and society. The primary pathological hallmarks of AD are β-amyloid plaque (Aβ) deposition and neurofibrillary tangles. Notably, the cerebellum seems to be resilient to these pathological developments in the initial phases of AD. This early resistance of the cerebellum suggests it might contribute to compensating for the cognitive impairments associated with AD. Enhancing cerebellar reserve is a potential therapeutic approach. Repetitive transcranial magnetic stimulation (rTMS) has been explored as a means to achieve this, attributed to synaptic plasticity in the cerebellar cortex. Hypothesis: The cerebellar dentate nucleus (CDN), a crucial node for information transmission between the cerebellum and cerebral cortex, shows abnormal functional connectivity with cortex in AD patients. Preclinical studies demonstrated that stimulating lateral cerebellar nucleus, the rodent homologue of the human CDN, enhanced cognitive rehabilitation and improved cortical plasticity in animals after brain injury, suggesting CDN as a neuromodulation target for cognitive networks. We speculate that intermittent θ-burst stimulation (iTBS) based TMS targeting the cerebellar dentate nucleus may improve cognitive function, brain function, and lymphatic drainage in AD patients. Specific aims: In this study, we will conduct a randomized, double-blind, sham-controlled clinical trial focusing on the cerebellum with iTBS to assess its efficacy, safety and potential mechanisms in the treatment of AD patients. The findings yielded by the present project will have a potential strong impact on clinical practice of AD patients. Since rTMS is well tolerated and relatively low-priced, a positive result could lead to a fast application of the present proposal to the clinical experience. If successful, the proposed project will provide support for a novel treatment for cognitive dysfunction in AD patients.

The research team will first recruit 10 therapists and two supervisors from one CMH clinic in order to conduct a single-arm field trial of LyssnCBT. Each therapist will use the LyssnCBT platform with two clients over the course of two weeks (four total sessions per therapist). In addition, supervisors will conduct a supervision session with each therapist using the LyssnCBT tool's fidelity feedback. Next, participants will complete brief Likert assessments on technical reliability, functional reliability, and experiences integrating the system into the daily workflow. Usage data from LyssnCBT will be captured automatically by the system, including: which software features were used, time spent reviewing sessions and transcripts, and time spent reviewing artificial intelligence (AI) generated CBT fidelity feedback. This data and feedback will be used for a final refinement of the LyssnCBT software and related clinical and supervision protocols prior to the main trial. Following the pilot study, the research team will recruit 4 additional CMH clinics to participate in a type 2 hybrid implementation-effectiveness, randomized stepped-wedge study comparing LyssnCBT to SAU. 50 therapists and their supervisors will be recruited from the participating clinics, and each therapist will be asked to have at least 5 clients participating in the study at any given time, from among their regular caseload. Across 18 months of planned data collection (\~75 weeks), the investigators expect a minimum of 1,875 clients for 50 therapists (i.e., 50 therapists x 5 sessions per week x 75 weeks = 18,750 sessions, with an average of 10 sessions per client). All 5 clinics will start with SAU, and clinics will be randomized to begin LyssnCBT sequentially over time. The primary data being collected throughout the project are recordings of therapy sessions, which are also collected as part of the typical operating procedures of the Penn Beck Community Initiative (BCI). CBT fidelity will be assessed by AI-generated Cognitive Therapy Rating Scale (CTRS) scores for every recorded therapy session, which will be recorded via the Lyssn platform during both SAU and LyssnCBT phases of the study. For client outcomes, the PHQ-9 and GAD-7 will be collected at each session and client drop-out will be assessed via a brief monthly survey sent out to participating therapists. Finally, after three months of engagement with the LyssnCBT tools, each participating therapist and supervisor will complete our battery of implementation measures, including the system usability scale, AIM, IAM, and FIM.

As an innovative non-invasive neuromodulation technology, repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in improving motor symptoms in patients with Parkinson's disease (PD). The supplementary motor area (SMA) has been identified as a brain region significantly associated with motor symptoms in PD patients. However, no large-sample clinical studies have yet established the clinical efficacy of rTMS, guided by neuroimaging navigation, targeting the SMA in patients with Parkinson's disease. We describe a open-lable study designed to recruit 20 patients with idiopathic Parkinson's disease. Participants will be randomly assigned to receive either real stimulation or sham stimulation, with the left SMA undergoing 7 days of continuous theta burst stimulation (cTBS). The primary outcome measure is the change in the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III scores from baseline to post-treatment and follow-up. Secondary outcomes include changes in scores on other clinical symptom scales.

This study is a Stage II randomized-controlled trial of a novel behavioral intervention, titled Behavioral Exposure for Interoceptive Tolerance (BE-FIT), to evaluate (1) its efficacy in improving exercise adherence in CR and (2) its mechanisms of change in individuals 40 years of age and older. One hundred and forty-six patients enrolled in Robert Wood Johnson University Hospital (RWJ) cardiac rehabilitation (CR) program who have elevated exercise anxiety, as indicated by endorsement of much to very much concern about at least 3 items on the Exercise Sensitivity Questionnaire (ESQ; Farris et al., 2020) and meet other eligibility criteria will be randomly assigned to either receive BE-FIT, a tailored intervention specifically for CR patients with high levels of exercise anxiety (n=73), or the health education condition (HEC; n=73), which are matched for contact time. Eligible participants will be stratified based on their risk profile (determined by their electronic health record), age, sex, and ESQ score. These stratification variables were selected because they are associated with anxiety and fitness levels which could impact physical activity (PA) outcomes. Both conditions will be administered by trained doctoral-level students enrolled at Rutgers University and will be supervised throughout the course of the study by Dr. Farris and other listed co-investigators. The BE-FIT intervention is a cognitive-behavioral intervention and is designed to target exercise anxiety. The three main components of BE-FIT include: 1) exposure to feared bodily sensations and exercise, 2) prevention of safety behavior use before/during/after exercise, and 3) use of a wrist-worn activity monitor (Fitbit) for PA feedback and activity goal setting. The alternative type of intervention is the Health Education Control (HEC), which is a time-matched control intervention that will be delivered on the same delivery schedule as BE-FIT. The doctoral-level clinicians who will be delivering HEC will be exclusively trained in order to avoid contamination with the BE-FIT intervention. In this control arm, participants will be provided educational information about health topics relevant to healthy aging delivered through PowerPoint lectures and handouts and use a Fitbit for PA monitoring. The HEC protocol has been used in prior studies conducted by Dr. Abrantes (co-investigator). The overall duration of the study is 24 weeks, or approximately 6 months. Subjects will be involved in 6 individual sessions delivered twice weekly during the initial weeks of outpatient CR. Sessions occur for 45 minutes either immediately before or after regularly scheduled CR sessions. Five independent assessments are conducted at baseline, EOT, and three follow-ups (Weeks 12, 18, 24). Data collection will occur at each visit, with baseline data collected at the initial visit.

This study is a clinical, longitudinal, non-randomized, prospective observational study that seeks to compare the treatment effects and safety of using GLP-1 analogues versus not using appetite suppressants during a lifestyle treatment program that includes individual consultations every fourth month and 10 weeks of CBT-E group therapy in patients with both obesity and BED. The primary objective of this study is to evaluate the impact on BED symptomatology, while the secondary objectives include examining the potential adoption of alternative harmful coping mechanisms. Additionally, the study will assess psychological well-being and weight changes and their consequent influence on obesity-associated comorbid conditions. Adult patients with coexisting obesity and BED presenting at the Obesity clinic at Haukeland University Hospital, Bergen, Norway, will be included Patients will be divided into two groups: Group-GLP1 (n = 40), who will use GLP-1 analogues, and Group-NoMED (n = 40), who will not use appetite suppressants. Both groups will otherwise follow the routine standardized patient care pathway with follow-up controls every four months and participation in CBT group therapy sessions. Changes in symptoms of BED, alternative harmful coping strategies and mental health will be recorded at baseline and 12 months using patient-reported questionnaires, as well as anthropometric and biochemical data.

Cognitive aging and associated pathologies, primarily dementia and its main cause Alzheimer's disease, are a major public health issue. Because of the under-diagnosis of dementia in the population and the very long preclinical phase of these diseases, population-based cohorts are essential to better understand brain aging. With the PAQUID and 3-Cités cohorts, the Bordeaux Population Health Research Center (BPH) has been a world pioneer in population-based studies on aging and dementia, and has thus contributed greatly to a better understanding of age-realted brain diseases. As these cohorts are aging, and in view of the importance of studying the early stages of brain aging, it seems essential to continue our research efforts for the prevention of cognitive aging with the establishment of a new cohort of young seniors. In addition to the population-based design of the study, the representativeness of the cohort appears to be a crucial issue (since population-based cohorts depend on the voluntary participation of healthy individuals, unfavorable exposures and altered health states are often largely under-represented, which reduces the variability of exposures and events, leading to an underestimation of prevalences, a decrease in statistical power and a potential bias in the estimation of associations). Finally, the multifactorial nature of brain ageing pathologies now calls for the replacement of the reductionist approach of risk factors by a more holistic vision of the exposome (defined as all the environmental exposures with which an individual is confronted throughout the lifecourse). The development of an integrated approach of complex, high-dimensional, multi-omics biological data (genomics, transcriptomics, epigenomics, metabolomics, proteomics), applied to various biological matrices, is an indispensable tool to deep phenotyping and to the establishment of a new generation etiological epidemiological research framework in the field of brain aging pathologies. The Biobank and Brain health in Bordeaux cohort (B cube) will include the completion of a general questionnaire (during the V1 visit), a dietary survey (during the V1, V4 and V5 visits), a computerized cognitive battery (during the V1 visit), a collection of biological material (blood, urine, stool, saliva, hair, nails and nasopharyngeal swab) for the constitution of a biobank (during the V2 biobank visit, 2000 samples of blood, urine, hair, nails and 1000 samples expected for the other fluids/samples) An MRI will be performed in volunteers aged 55 to 70 years (during the V3 visit). Finally, a complementary visit by a medical specialist may be proposed to participants with cognitive disorders or Parkinson's syndrome. Approximately three years after V1, a follow-up phase is proposed to the participant, comprising a block of 6 visits: a general questionnaire accompanied by a computerized cognitive battery (V7), a dietary survey (V7, V9, V10 and V11), a new collection of biological material (V8) including blood samples and hair (for all participants in the follow-up phase) and stool samples (if sampling had not taken place during V2 and for a subsample of participants at follow-up).

To study effects, the investigators aim to conduct a randomized controlled trial (RCT) comparing blended treatment to an evidence-based face-to-face TF-CBT protocol, Prolonged exposure. Data will be collected concerning symptoms of PTSD with the PTSD Checklist for Diagnostic and Statistical Manual 5 (DSM-5; PCL-5) which will be the primary outcome measure. Further, symptoms of PTSD will be measured with Clinician-administered PTSD Scale for DSM-5 (CAPS-5), depression The PHQ-9, symptoms of anxiety with GAD-7 , quality of life with Work and social adjustment scale (WSAS), and sleep with the insomnia severity index (ISI). Outcome measures will be distributed before, during, after, as well as 12-months following treatment. In accordance with CONSORT recommendations for non-inferiority trials, both intention-to-treat (ITT) and per-protocol (PP) analyses will be performed and reported for the primary non-inferiority comparisons. Secondary outcomes will be analyzed using ITT principles. ITT population All randomized participants who completed the pre-treatment assessment and participated in the inclusion session. PP population The PP population will include participants who have received at least 50% of the planned total treatment dose, defined across both digital modules and face-to-face sessions in the blended format. Demographic variables Basic demographic variables (e.g., age, gender, education, trauma history, employment, and comorbid psychiatric disorders) will be collected at baseline. Therapist competence and fidelity Therapist competence and adherence to PE and blended TF-CBT protocols will be assessed using structured fidelity checklists. A subset of recorded sessions will be rated by independent assessors. Inter-rater reliability for CAPS-5 Interrater reliability will be assessed by having all CAPS raters independently score the same recorded role-play CAPS interview, with agreement evaluated using intraclass correlation coefficients (ICC), both between raters and relative to a predefined reference rating Protocol deviations and adverse events Protocol deviations and adverse events (e.g., treatment interruptions, medication changes, unexpected events) will be documented and summarized descriptively. Treatment dose and engagement Treatment engagement (e.g., number of sessions, digital module completion, total therapeutic time, and treatment duration) will be recorded to describe dose and support per-protocol analyses. Concurrent treatments Participants will be asked about any concurrent psychological or pharmacological treatment at follow-up assessments. To analyze the data, a non-inferiority analysis will be applied for the primary outcome variable. Step one in this analysis will be to determine what difference in mean scores on the PCL-5 between the two treatments is tolerated to conclude that the experimental intervention is non-inferior to the standard treatment (non-inferiority margin). Continuous outcomes will be analysed using linear mixed models, and non-inferiority will be assessed based on the 95% confidence interval for the estimated mean difference between treatments. Non-inferiority will be concluded if the lower bound of the confidence interval for the experimental treatment (bTF-CT) is above the predefined non-inferiority margin. If this criterion is met, the experimental treatment will be interpreted as non-inferior to the standard treatment (TF-CBT). The non-inferiority margin was determined using procedures recommended in methodological guidelines for non-inferiority trials. One approach was based on preservation of a proportion of the established effect of the active control. Specifically, a pooled effect size of 1.0 for prolonged exposure therapy (PE) was identified from a published meta-analysis. In accordance with recommended practice, 50% of this effect was retained to define the non-inferiority margin, corresponding to a Cohen's d of 0.5. To adopt a more conservative approach and to ensure that the margin remained below the conventional threshold for a medium-sized effect, the non-inferiority margin was therefore set to Cohen's d = 0.4. Assuming a standard deviation of 15.98 on the PCL-5, based on post-treatment values from a comparable reference study, this corresponds to an absolute mean difference of approximately 7 points on the PCL-5. This value was therefore selected as the non-inferiority margin. As an additional check of clinical plausibility, the selected margin was compared with previously established estimates of the minimal important difference (MID) for the PCL-5, which have been reported to be approximately 9 points, indicating that the chosen margin was conservative. Further, to estimate the required sample size, rigorous power calculations were carried out in collaboration with an expert in statistical analysis, applying a simulation-based approach using a 2-level linear mixed-effects model, using estimates from the reference TF-CBT, looking at six assessment points. Variance components that were incorporated into the analysis were random intercept, random slopes and residual variance. The power calculation showed that with 78 participants in each treatment group and a 20% dropout rate, 80% power is reached, given a non-inferiority margin of 7 points and α = 0.05. An interim power analysis was also conducted by an external analyst, using model parameters from observed data in the power analysis, while also updating the number of assessment points to 16 and using α = 0.025. This resulted in 70 participants per group with power \> 80%. To allow for per-protocol analysis, we will aim for 160 participants in total. Continuous outcomes will be analyzed using linear mixed models (LMM) with an appropriate distribution family. Model checks for residuals and outliers will be performed using the R packages 'DHARMa' and 'performance' with default settings. If outliers are identified, this will be handled by using a robust LMM. Time in weeks will be treated as a continuous linear variable. The baseline measurement will be used as a covariate, modeled with a restricted cubic or natural spline. If time is found to be non-linear, it will also be modeled using splines. Confidence intervals will be generated using bootstrap. The mean difference between intervention groups (average treatment effect) will be estimated for the post-treatment measurement point using g-estimation. In the main analysis, treatment site will be added as a fixed effect covariate interacted with the treatment variable, and a therapist variable using a random slope only. This analysis will be conducted both using intent-to-treat (ITT) and per-protocol (PP). Missing data will be handled by multiple imputation with chained equations, imputing 20 datasets for analysis and pooling results. If there are differences in adherence between treatment groups for the PP analysis, a more robust method will be used, such as inverse probability of treatment weighting of instrumental variables(1). The investigators will also calculate effect sizes using Cohen's d based on pooled standard deviations. Following regulatory recommendations (2), a baseline covariate-adjusted analysis will also be conducted and reported. This model will use the ANHECOVA approach, where all covariates interact with the treatment variable. Planned covariates that are added compared to the main analysis are: age, gender, education level, depression score, insomnia severity index score, work and social adjustment scale score, and trauma during childhood. Continuous baseline variables will be grand mean centered. Bootstrap will be used for confidence intervals. This analysis will only use ITT. Sensitivity analyses will be conducted. One model will include only baseline, mid-treatment and post-treatment measurement points, since these are expected to have much lower attrition compared to weekly measurements. We will use a mixed model for repeated measurements (MMRM) with an unstructured covariance matrix. This model will also be fitted using both ITT and PP. The credibility and expectancy scale (CEQ), measured 2 weeks post-treatment start, will be used as a covariate in one model to evaluate potential effects of CEQ on the primary outcome. This model will also include the list of covariates specified in the previous paragraph. Dichotomous variables that will be analyzed as outcomes: Remission rates will be calculated using a cut off of 31 on the PCL-5, across time in weeks; having a PTSD diagnosis according to CAPS-5 at time points pre, post, 6- and 12-months follow-up; and the proportion of patients who will show treatment response on the PCL-5, defined as a reduction of at least 10 points from baseline. All dichotomous outcomes will be analyzed using mixed model logistic regressions and comparisons between treatment groups will be reported as incident rate ratios and/or risk differences. Dichotomous data of remission will also be analyzed with survival analysis where time to remission is calculated and compared between groups. 1. Dodd M, Carpenter J, Thompson JA, et al. Assessing efficacy in non-inferiority trials with non-adherence to interventions: Are intention-to-treat and per-protocol analyses fit for purpose? Stat Med 2024; 43: 2314-2331. DOI: https://doi.org/10.1002/sim.10067. 2. Ye T, Shao J, Yi Y, et al. Toward Better Practice of Covariate Adjustment in Analyzing Randomized Clinical Trials. Journal of the American Statistical Association 2023; 118: 2370-2382. DOI: 10.1080/01621459.2022.2049278.