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Background: Alcohol misuse is common and causes substantial harm. Internet-delivered cognitive behaviour therapy (ICBT) is effective in reducing alcohol misuse; however, the literature investigating how treatment outcomes are impacted by patients' preferences for therapist- versus self-guided ICBT for alcohol misuse is sparse., Methods: In this preference trial, 74 eligible patients (who reported ≥ 14 drinks in the previous week and obtained scores suggesting hazardous or harmful drinking) chose between enrolling in either therapist- or self-guided ICBT for alcohol misuse. We investigated whether those who chose therapist- versus self-guided ICBT differed in their (a) drinking outcomes-as measured by Timeline Follow-Back (TLFB) and heavy drinking days (HDD) at post-treatment and 3-month follow-up-and (b) post-treatment ICBT engagement and satisfaction., Results: The majority (81.1%) of eligible patients chose therapist-guided ICBT. These patients reported higher psychotropic medication use, drinking difficulties, and anxiety symptoms. For both the therapist- and self-guided patients, a modified intention-to-treat analysis revealed large within-group treatment effects for TLFB (β =  - 2.64, SE 0.66; p < 0.001) and HDD (β =  - 0.34, SE 0.07; p < 0.001), with large pre-to-post-treatment Cohen's effect sizes of d = 0.97 (95% CI [0.49, 1.45]) for TLFB and d = 1.19 (95% CI [0.69, 1.68]) for HDD. The interaction comparing the effects of therapist- to self-guided ICBT over time was not significant for TLFB (p = 0.34) or HDD (p = 0.06). With treatment, for both therapist- and self-guided patients, there was a significant improvement in drinking difficulties, cravings, and confidence with controlling cravings, as well as in anxiety, depression, and functional impairment. Further, the majority (75.7%) of patients completed five or more lessons, as well as reported overall satisfaction with the treatment (88.9%) and increased confidence in managing their symptoms (86.7%); these outcomes also did not differ between therapist- and self-guided patients., Conclusions: The current study shows that ICBT for alcohol misuse is associated with reduced drinking and comorbid mental health difficulties over time, irrespective of whether patients chose to complete the course on their own or with therapist guidance., Trial Registration Number: NCT04611854 ( https://clinicaltrials.gov/ct2/show/NCT04611854 )., (© 2024. The Author(s).)

The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.

Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components., Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned., Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group., (© 2024. The Author(s).)

Background: The continual development and implementation of effective digital interventions is one important strategy that may serve to bridge the well-known treatment gap related to problematic alcohol use. Research suggests that clinician guidance, provided in different ways during the digital intervention (i.e., written weekly messages, phone calls etc.), can boost intervention engagement and effects. Digital psychological self-care (DPSC) is a new delivery format wherein an unguided digital intervention is provided within the framework of a structured care process that includes initial clinical assessment and follow-up interviews. In a recent feasibility study, a DPSC intervention for problematic alcohol use, ALVA, provided without any extra guidance, was found safe and credible and to have promising within-group effects on alcohol consumption. The aim of the current study is to gather information on the effects and efficiency of different forms of guidance added to ALVA, in order to optimize the intervention., Methods: This protocol describes a randomized factorial trial where the effects of two different ways of providing guidance (mid-treatment interview, weekly written messages, respectively) in DPSC for problematic alcohol use are investigated. Optimization criteria will be applied to the results regarding how effective the intervention is at reducing alcohol consumption measured by the number of standard drinks per week together with the clinician time spent on guidance., Discussion: This study will investigate the added benefit of different forms of guidance to DPSC for problematic alcohol use. These added effects will be compared to the added cost of guidance, according to pre-defined optimization criteria., Trial Registration: Clinicaltrials.gov: NCT05649982. Registered on 06 December 2022. Prospectively registered., (© 2024. The Author(s).)