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Abstract Background Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. Methods This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). Discussion The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. Trial registration Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

This systematic review aimed to synthesize evidence on predictors and moderators of treatment outcomes in internet- and mobile-based interventions (IMIs) for depression, informing personalized care. A systematic search across PubMed, PsycInfo, and Cochrane yielded 33,002 results. Two reviewers independently performed screening, data extraction, risk of bias assessment, and methodological quality evaluation. Fifty-eight single studies (m = 466 analyses) focusing on baseline-predictors (59.7 %, m = 278), process-predictors (16.5 %, m = 77), and moderators (21.9 %, m = 102), and six individual patient data meta-analyses (m = 93) were included. Only 24.0 % (m = 112/466) of analyses in single studies and 15.1 % (m = 14/93) in individual patient data meta-analyses were significant. Evidence from single studies was rated as insufficient for all variable categories with only 2 out of 40 categories showing >50 % significant results. Baseline depression severity had the strongest predictive value with higher scores linked to better outcomes followed by variables indicative for the course-of-change. Other frequently analyzed and potentially relevant variables with significant results were adherence, age, educational level, ethnicity, relationship status, treatment history, and behavioral variables. More high quality quantitative studies with sufficient power are essential to validate and expand findings, identifying predictors and moderators specifically relevant in IMIs to explain differential treatment effects.

The article presents the results of the study and analysis of archival documents, on the basis of which the history of the construction of the complex of buildings of the garrison infirmary «York» in Königsberg is recreated, the features of the architectural and planning solutions used in the construction of this medical complex are studied and analyzed. The description of the post-war and modern stages of development of the infectious diseases hospital of the Kaliningrad region, which is located in the preserved buildings of the garrison infirmary «York» in Konigsberg, is given.

Background: It is uncertain whether app-based interventions add value to existing mental health care. Objective: To examine the incremental effects of app-based interventions when used as adjunct to mental health interventions. Methods: We searched PubMed, PsycINFO, Scopus, Web of Science, and Cochrane Library databases on September 15th, 2023, for randomised controlled trials (RCTs) on mental health interventions with an adjunct app-based intervention compared to the same intervention-only arm for adults with mental disorders or respective clinically relevant symptomatology. We conducted meta-analyses on symptoms of different mental disorders at postintervention. PROSPERO, CRD42018098545. Results: We identified 46 RCTs (4869 participants). Thirty-two adjunctive app-based interventions passively or actively monitored symptoms and behaviour, and in 13 interventions, the monitored data were sent to a therapist. We found additive effects on symptoms of depression (g = 0.17; 95 % CI 0.02 to 0.33; k = 7 comparisons), anxiety (g = 0.80; 95 % CI 0.06 to 1.54; k = 3), mania (g = 0.2; 95 % CI 0.02 to 0.38; k = 4), smoking cessation (g = 0.43; 95 % CI 0.29 to 0.58; k = 10), and alcohol use (g = 0.23; 95 % CI 0.08 to 0.39; k = 7). No significant effects were found on symptoms of depression within a bipolar disorder (g = -0.07; 95 % CI -0.37 to 0.23, k = 4) and eating disorders (g = -0.02; 95 % CI -0.44 to 0.4, k = 3). Studies on depression, mania, smoking, and alcohol use had a low heterogeneity between the trials. For other mental disorders, only single studies were identified. Only ten studies had a low risk of bias, and 25 studies reported insufficient statistical power. Discussion: App-based interventions may be used to enhance mental health interventions to further reduce symptoms of depression, anxiety, mania, smoking, and alcohol use. However, the effects were small, except for anxiety, and limited due to study quality. Further high-quality research with larger sample sizes is warranted to better understand how app-based interventions can be most effectively combined with established interventions to improve outcomes.

ABSTRACTHuman cytomegalovirus (HCMV) is a highly prevalent viral pathogen that typically presents asymptomatically in healthy individuals despite lifelong latency. However, in 10%–15% of congenital cases, this beta-herpesvirus demonstrates direct effects on the central nervous system, including microcephaly, cognitive and learning delays, and hearing deficits. HCMV has been widely shown to infect neural progenitor cells, but the permissiveness of fully differentiated neurons to HCMV is controversial and chronically understudied, despite potential associations between HCMV infection and neurodegenerative conditions. Using a model system representative of the human forebrain, we demonstrate that induced pluripotent stem cell-derived excitatory glutamatergic and inhibitory GABAergic neurons are fully permissive to HCMV with complete viral replication, competent virion production, and spread within the culture. Interestingly, while cell proliferation was not induced in these post-mitotic neurons, HCMV did increase expression of proliferative markers Ki67 and proliferative cell nuclear antigen suggesting alterations in cell cycle machinery. These findings are consistent with previous HCMV-mediated changes in various cell types and implicate the ability of viral proteins to alter proliferative pathways to promote virion production. Infection also induces significant structural changes in forebrain neurons, such as the formation of syncytia and the retraction of neurites. Finally, we demonstrate that HCMV disrupts calcium signaling and decreases neurotransmission, with action potential generation effectively silenced after 15 days post-infection. Taken together, our data highlight the potential for forebrain neurons to be permissive to HCMV infection in the central nervous system, which has significant implications for overall brain health and function.IMPORTANCEHuman cytomegalovirus (HCMV) is a highly prevalent viral pathogen that can cause serious neurological deficits in infants experiencing an in utero infection. Also, as a life-long infection, HCMV has been associated with several diseases in the adult brain. HCMV is known to infect early neural progenitor cells, but whether it also infects terminally differentiated neurons is still debated. Here, we differentiated human-induced pluripotent stem cells into neurons for 84–120 days to test the ability of HCMV to infect terminally differentiated neurons and assess the downstream functional consequences. We discovered that mature human neurons are highly permissive to HCMV infection, exhibited late replication hallmarks, and produced infectious virus. Moreover, infection in terminally differentiated neurons essentially eliminated neuron function. These results demonstrate that terminally differentiated human neurons are permissive to HCMV infection, which can significantly alter both structural and functional features of this mature neuron population.

Low-threshold and remotely delivered preventive interventions, like telephone coaching, are warranted for farmers who experience multiple risk factors for depression, live in underserved areas, and show low help-seeking behavior. Factors facilitating uptake and actual use of effective remote interventions are important to reduce depression disease burden. This study aimed at identifying factors that potentially can influence acceptance of and satisfaction with a telephone coaching in this occupational group.Semi-structured interviews were based on the ‘Unified Theory of Acceptance and Use of Technology’, the ‘Evaluation’, and ‘Discrepancy’ models for satisfaction. Interviews were conducted with 20 of 66 invited participants of a 6-months telephone coaching during an effectiveness or implementation study. Audio-recorded interviews were transcribed and analyzed (deductive-inductive qualitative content analysis). Independent coding by two persons resulted in good agreement (Κ = 0.80). Participants validated results via questionnaire.Overall, 32 supporting (SF) and 14 hindering factors (HF) for acceptance and satisfaction were identified and organized into five dimensions: Coaching result (SF = 9, HF = 3), coach (SF = 9, HF = 1), organization (SF = 5, HF = 2), the telephone as communication medium (SF = 4, HF = 5) and participant characteristics (SF = 5, HF = 3). Most named SFs were ‘Flexible appointment arrangement’ (n = 19/95 %) and ‘low effort’ (n = 17/85 %), while most reported HFs were ‘lack of visual cues’ (n = 12/60 %) and ‘social/professional involvement restricts change process’ (n = 10/50 %).The perceived changes initiated by coaching, a low effort through telephone conduct, and the indicated personalization were identified as important influencing factors on acceptance and satisfaction based on interviewees' statements. Both may be further enhanced by offering choice and advice for delivery formats (e.g., video-calls) and training of coaches in farm-related issues. Study registration: German Clinical Trial Registrations: DRKS00017078 and DRKS00015655.

Abstract Background Endometriosis is a benign, hormone-dependent, chronic inflammatory gynecological disease accompanied by cyclic and acyclic pelvic pain and other complaints. The long lists of research recommendations in the AWMF guideline (Burghaus et al., Geburtshilfe Frauenheilkd 81:422–46, 2021) and ESHRE Endometriosis Guideline (ESHRE Endometriosis Guideline Development Group, Endometriosis: Guideline of European Society of Human Reproduction and Embryology, 2022) show that there is still a great need for research in all aspects of the disease. Diagnostic delay, defined as the mean time between symptom onset and confirmed diagnosis, is a particular problem associated with endometriosis. Some quantitative and qualitative studies have investigated possible reasons for this. A range of physician-related (Dixon et al., Br J Gen Pract 71:e668-e676, 2021; van der Zanden and Nap, Reprod Biomed Online 32:527–31, 2016) and patient-related factors (Sayer-Jones and Sherman, Health Psychol Behav Med 9:456–79, 2021) as well as stigmatization of the topic of menstruation by society have been identified (Kruckenberg, Frauenarzt 59:2–5, 2018; Seear, Soc Sci Med 69:1220–7, 2009). The consequences of the disease being diagnosed late (or too late) on the course of disease, the quality of life and the costs of the disease have already been documented in studies (Sims Int J Environ Res Public Health 18(15):8210, 2021; Surrey Adv Ther 37:1087–99, 2020). However, a systematically derived cut-off value that clearly distinguishes between short and long delay is still lacking. Therefore, the aim of our study was to derive a threshold value for the definition of a target corridor for endometriosis diagnosis based on descriptive and analytical methods. Methods Since our review of the rather sparse publications on diagnostic delay did not yield satisfactory results, we used descriptive statistics and location parameters to calculate a cut-off value for German population data from the EndoCost study. Statistical methods were used for correlation analysis of shortDD versus longDD (correlation analysis and logistic regression) and group membership (discriminant analysis). Results Five years was identified as the cut-off value that significantly differentiated between shortDD and longDD based on various disease-related variables. This suggests that endometriosis should be definitively diagnosed within less than five years to minimize the risk of an unfavorable course of the disease. Conclusion Our findings confirmed that an early onset of endometriosis-related symptoms is the most important risk factor for a long diagnostic delay. Consequently, adolescent females should receive increased attention as an especially vulnerable group. Evidently, there is an urgent need to develop adequate concepts to improve the endometriosis education and care among this target group.

Objective Mental health self-report and clinician-rating scales with diagnoses defined by sum-score cut-offs are often used for depression screening. This study investigates whether machine learning (ML) can detect major depressive episodes (MDE) based on screening scales with higher accuracy than best-practice clinical sum-score approaches. Methods Primary data was obtained from two RCTs on the treatment of depression. Ground truth were DSM 5 MDE diagnoses based on structured clinical interviews (SCID) and PHQ-9 self-report, clinician-rated QIDS-16, and HAM-D-17 were predictors. ML models were trained using 10-fold cross-validation. Performance was compared against best-practice sum-score cut-offs. Primary outcome was the Area Under the Curve (AUC) of the Receiver Operating Characteristic curve. DeLong's test with bootstrapping was used to test for differences in AUC. Secondary outcomes were balanced accuracy, precision, recall, F1-score, and number needed to diagnose (NND). Results A total of k = 1030 diagnoses (no diagnosis: k = 775; MDE: k = 255) were included. ML models achieved an AUC QIDS-16 = 0.94, AUC HAM-D-17 = 0.88, and AUC PHQ-9 = 0.83 in the testing set. ML AUC was significantly higher than sum-score cut-offs for QIDS-16 and PHQ-9 ( ps ≤ 0.01; HAM_D-17: p = 0.847). Applying optimal prediction thresholds, QIDS-16 classifier achieved clinically relevant improvements (Δbalanced accuracy = 8%, ΔF1-score = 14%, ΔNND = 21%). Differences for PHQ_9 and HAM-D-17 were marginal. Conclusions ML augmented depression screenings could potentially make a major contribution to improving MDE diagnosis depending on questionnaire (e.g., QIDS-16). Confirmatory studies are needed before ML enhanced screening can be implemented into routine care practice.

Given prevalent alcohol misuse-emotional comorbidities among young adults, we developed an internet-based integrated treatment called Take Care of Me. Although the treatment had an impact on several secondary outcomes, effects were not observed for the primary outcome. Therefore, the goal of the current study was to examine heterogeneity in treatment responses. The initial RCT randomized participants to either a treatment or psychoeducational control condition. We conducted an exploratory latent class analysis to distinguish individuals based on pre-treatment risk and then used moderated regressions to examine differential treatment responses based on class membership. We found evidence for three distinct groups. Most participants fell in the “low severity” group (n = 123), followed by the “moderate severity” group (n = 57) who had a higher likelihood of endorsing a previous mental health diagnosis and treatment and higher symptom severity than the low group. The “high severity” group (n = 42) endorsed a family history of alcoholism, and the highest symptom severity and executive dysfunction. Moderated regressions revealed significant class differences in treatment responses. In the treatment condition, high severity (relative to low) participants reported higher alcohol consumption and hazardous drinking and lower quality of life at follow-up, whereas moderate severity (relative to low) individuals had lower alcohol consumption at follow-up, and lower hazardous drinking at end-of-treatment. No class differences were found for participants in the control group. Higher risk individuals in the treatment condition had poorer responses to the program. Tailoring interventions to severity may be important to examine in future research.

IntroductionDigital health interventions are an effective way to treat depression, but it is still largely unclear how patients’ individual symptoms evolve dynamically during such treatments. Data-driven forecasts of depressive symptoms would allow to greatly improve the personalisation of treatments. In current forecasting approaches, models are often trained on an entire population, resulting in a general model that works overall, but does not translate well to each individual in clinically heterogeneous, real-world populations. Model fairness across patient subgroups is also frequently overlooked. Personalised models tailored to the individual patient may therefore be promising.MethodsWe investigate different personalisation strategies using transfer learning, subgroup models, as well as subject-dependent standardisation on a newly-collected, longitudinal dataset of depression patients undergoing treatment with a digital intervention (N=65 patients recruited). Both passive mobile sensor data as well as ecological momentary assessments were available for modelling. We evaluated the models’ ability to predict symptoms of depression (Patient Health Questionnaire-2; PHQ-2) at the end of each day, and to forecast symptoms of the next day.ResultsIn our experiments, we achieve a best mean-absolute-error (MAE) of 0.801 (25% improvement) for predicting PHQ-2 values at the end of the day with subject-dependent standardisation compared to a non-personalised baseline (MAE=1.062). For one day ahead-forecasting, we can improve the baseline of 1.539 by 12% to a MAE of 1.349 using a transfer learning approach with shared common layers. In addition, personalisation leads to fairer models at group-level.DiscussionOur results suggest that personalisation using subject-dependent standardisation and transfer learning can improve predictions and forecasts, respectively, of depressive symptoms in participants of a digital depression intervention. We discuss technical and clinical limitations of this approach, avenues for future investigations, and how personalised machine learning architectures may be implemented to improve existing digital interventions for depression.

IntroductionThe efficacy and effectiveness of digital interventions for depression are both well-established. However, precise effect size estimates for mediators transmitting the effects of digital interventions are not available; and integrative insights on the specific mechanisms of change in internet- and mobile-based interventions (IMIs)—as related to key features like delivery type, accompanying support and theoretical foundation—are largely pending.ObjectiveWe will conduct a systematic review and individual participant data meta-analysis (IPD-MA) evaluating the mediators associated with therapeutic change in various IMIs for depression in adults.MethodsWe will use three electronic databases (i.e., Embase, Medline/PubMed, PsycINFO) as well as an already established database of IPD to identify relevant published and unpublished studies. We will include (1) randomized controlled trials that examine (2) mediators of (3) guided and unguided (4) IMIs with (5) various theoretical orientations for (6) adults with (7) clinically relevant symptoms of depression (8) compared to an active or passive control condition (9) with depression symptom severity as primary outcome. Study selection, data extraction, as well as quality and risk of bias (RoB) assessment will be done independently by two reviewers. Corresponding authors of eligible primary studies will be invited to share their IPD for this meta-analytic study. In a 1-stage IPD-MA, mediation analyses (e.g., on potential mediators like self-efficacy, emotion regulation or problem solving) will be performed using a multilevel structural equation modeling approach within a random-effects framework. Indirect effects will be estimated, with multiple imputation for missing data; the overall model fit will be evaluated and statistical heterogeneity will be assessed. Furthermore, we will investigate if indirect effects are moderated by different variables on participant- (e.g., age, sex/gender, symptom severity), study- (e.g., quality, studies evaluating the temporal ordering of changes in mediators and outcomes), and intervention-level (e.g., theoretical foundation, delivery type, guidance).DiscussionThis systematic review and IPD-MA will generate comprehensive information on the differential strength of mediators and associated therapeutic processes in digital interventions for depression. The findings might contribute to the empirically-informed advancement of psychotherapeutic interventions, leading to more effective interventions and improved treatment outcomes in digital mental health. Besides, with our novel approach to mediation analyses with IPD-MA, we might also add to a methodological progression of evidence-synthesis in psychotherapy process research.Study registration with Open Science Framework (OSF)https://osf.io/md7pq/.

Abstract Background Trachomatous scarring (TS) results from repeated infection with the bacterium Chlamydia trachomatis. Pronounced scarring is an underlying cause of trachomatous trichiasis (TT) that can lead to blindness. Since the condition is irreversible, TS in adults has been considered a marker of past exposure to trachoma infection. The aim of this report was to estimate the population-based prevalence of TS within Amhara, Ethiopia, a region with a historically high burden of trachoma. Methods District-level multi-stage cluster surveys were conducted in all districts between 2010 and 2015 to monitor the impact of approximately 5 years of trachoma interventions. Approximately 40 households were sampled per cluster and all participants ages ≥ 1 year were graded for the 5 World Health Organization simplified signs. Before each survey round, trachoma graders participated in a 7-day training and reliability exam that included cases of TS. TS prevalence estimates were weighted to account for sampling design and adjusted for age and sex using post-stratification weighting. Results Across the 152 districts in Amhara, 208,510 individuals ages 1 year and older were examined for the signs of trachoma. Region-wide, the prevalence of TS was 8.2 %, (95 % Confidence Interval [CI]: 7.7–8.6 %), and the prevalence among individuals ages 15 years and older (n = 110,137) was 12.6 % (95 % CI: 12.0–13.3 %). District-level TS prevalence among individuals ages 15 years and older ranged from 0.9 to 36.9 % and was moderately correlated with district prevalence of TT (r = 0.31; P

Abstract Background Depressive disorders and problematic drinking often co-occur, also among young adults. These co-occurring conditions are associated with various negative health outcomes compared to both conditions alone. Early intervention by addressing alcohol use and depressive symptoms simultaneously in the same treatment might improve both conditions. However, evidence on the (cost-) effectiveness of digital combined depression and alcohol interventions for young adults is currently insufficient. We therefore developed an add-on digital alcohol moderation adherence-focussed guided intervention to complement treatment as usual (TAU) for depressive disorders. The digital intervention is a web-app, including 6 modules based on motivational interviewing and cognitive behavioural therapy. This study aims to evaluate the (cost-)effectiveness of a digital alcohol moderation intervention + TAU compared to TAU on alcohol and depression outcomes among young adults with co-occurring depressive disorders and problematic alcohol use. Methods One hundred fifty-six participants, aged 18–35 years, with problematic alcohol use and a diagnosed depressive disorder will participate in a pragmatic multicentre two-arm randomized controlled trial. Problematic alcohol use is operationalised as scoring ≥5 for women and ≥ 8 for men on the Alcohol Use Disorder Identification Test (AUDIT). Participants will be randomized to either the experimental group (digital alcohol intervention + TAU) or control group (TAU only). Participants will be recruited at three Dutch mental health care centres and through social media. Assessments take place at baseline and after 3, 6 and 12 months post-randomization. The primary outcome is treatment response at 6-month follow-up, operationalized as a composite score that combines alcohol use and depression measures and indicates whether treatment has been successful or not. Secondary outcomes are depressive symptoms and alcohol use (i.e. number of weekly standard drinks and AUDIT score). An economic evaluation will be conducted alongside the trial. Discussion This study evaluates the (cost-) effectiveness of an add-on digital alcohol moderation intervention for young adults who are in treatment for depressive disorders. If proven effective, the digital intervention could be implemented in mental health care and improve treatment for people with co-occurring depressive disorders and problematic alcohol use. Trial registration Pre-registered on October 29, 2019 in The Netherlands Trial Register ( NL8122 ).

BackgroundPrevalence rates for lifetime cannabis use and cannabis use disorder are much higher in people with attention deficit/hyperactivity disorder than in those without. CANreduce 2.0 is an intervention that is generally effective at reducing cannabis use in cannabis misusers. This self-guided web-based intervention (6-week duration) consists of modules grounded in motivational interviewing and cognitive behavioral therapy. ObjectiveWe aimed to evaluate whether the CANreduce 2.0 intervention affects cannabis use patterns and symptom severity in adults who screen positive for attention deficit/hyperactivity disorder more than in those who do not. MethodsWe performed a secondary analysis of data from a previous study with the inclusion criterion of cannabis use at least once weekly over the last 30 days. Adults with and without attention deficit/hyperactivity disorder (based on the Adult Attention deficit/hyperactivity disorder Self-Report screener) who were enrolled to the active intervention arms of CANreduce 2.0 were compared regarding the number of days cannabis was used in the preceding 30 days, the cannabis use disorder identification test score (CUDIT) and the severity of dependence scale score (SDS) at baseline and the 3-month follow-up. Secondary outcomes were Generalized Anxiety Disorder score, Center for Epidemiological Studies Depression scale score, retention, intervention adherence, and safety. ResultsBoth adults with (n=94) and without (n=273) positive attention-deficit/hyperactivity disorder screening reported significantly reduced frequency (reduction in consumption days: with: mean 11.53, SD 9.28, P

Summary: Human cytomegalovirus (HCMV) is a betaherpesvirus that can cause severe birth defects including vision and hearing loss, microcephaly, and seizures. Currently, no approved treatment options exist for in utero infections. Here, we aimed to determine the impact of HCMV infection on the transcriptome of developing neurons in an organoid model system. Cell populations isolated from organoids based on a marker for infection and transcriptomes were defined. We uncovered downregulation in key cortical, neurodevelopmental, and functional gene pathways which occurred regardless of the degree of infection. To test the contributions of specific HCMV immediate early proteins known to disrupt neural differentiation, we infected NPCs using a recombinant virus harboring a destabilization domain. Despite suppressing their expression, HCMV-mediated transcriptional downregulation still occurred. Together, our studies have revealed that HCMV infection causes a profound downregulation of neurodevelopmental genes and suggest a role for other viral factors in this process.

Background: College students face several sources of stress. Self-guided stress management interventions offer an excellent opportunity for scaling up evidence-based interventions for self-management of these stresses. However, little is known about the overall effects of these interventions. Increasing this understanding is essential because self-guided stress management interventions might be a cost-effective and acceptable way of providing help to this important segment of the population during a critical life course stage. Methods: We carried out a systematic literature search of bibliographical databases (PubMed, PsycINFO, Embase, and Cochrane Library) for randomized controlled trials (RCTs) of self-guided stress management interventions published up through April 2020. We conducted two separate meta-analyses for perceived stress, depression, and anxiety. The first included interventions for general college student samples. The second included studies for students with high levels of perceived stress. Results: The first meta-analysis included 26 studies with 29 intervention-control comparisons based on a total of 4468 students. The pooled effect size was small but statistically significant (g = 0.19; 95% CI [0.10, 0.29]; p

Chronic medical conditions are increasingly common and associated with a high burden for persons affected by them. Digital health interventions might be a viable way to support persons with a chronic illness in their coping and self-management. The present special issue's editorial on digital health interventions in chronic medical conditions summarizes core findings and discusses next steps needed to further the field while avoiding to reinvent the wheel, thereby elaborating on four topics extracted from the special issue's articles: 1) Needs assessment and digital intervention development, 2) Efficacy and (cost-)effectiveness, 3) Dissemination and implementation research: reach and engagement as well as 4) next generation of digital interventions.

Abstract Background College is an exciting but also challenging time with an increased risk for mental health issues. Only a minority of the college students concerned get professional help, a problem that might be improvable by internet- and mobile-based interventions (IMIs). However, adherence of IMIs is a concern. While guidance might be a solution, it is resource-intensive, derailing potential implementation on population level. The first aim of this trial is to evaluate the efficacy of the IMI StudiCare Mindfulness (StudiCare-M) for college students with “on demand” and no guidance. The second aim is to examine potential moderators and mediators, contributing to the questions of “how” and “for whom” such interventions work. Methods In this three-armed randomized controlled trial, both an unguided and “guidance on demand” (GoD) condition of StudiCare-M are compared to a waitlist control group. StudiCare-M is based on principles of acceptance and commitment therapy and stress management and consists of 7 modules plus two booster sessions. Participants in the GoD condition may ask their e-coach for support whenever needed. A total of 387 college students with moderate to low mindfulness are recruited at 15+ cooperating universities in Germany, Austria, and Switzerland via circular emails. Assessments take place before as well as 1, 2, and 6 months after randomization. The primary outcome is mindfulness. Secondary outcomes include stress, depression, anxiety, interoception, presenteeism, wellbeing, intervention satisfaction, adherence, and potential side effects. Among examined moderators and mediators are sociodemographic variables, pre-treatment symptomatology, treatment expectancy, self-efficacy, cognitive fusion, emotion regulation, and alexithymia. All data will be analyzed according to intention-to-treat (ITT) principles. Discussion Providing effective interventions to help college students become more resilient can make a valuable contribution to the health and functionality of future society. If effective under the condition of minimal or no guidance, StudiCare-M offers a low-threshold potentially resource-efficient possibility to enhance college student mental health on a population level. Moderation- and mediation analyses will deliver further insights for optimization of target groups and intervention content. Trial registration WHO International Clinical Trials Registry Platform via the German Clinical Studies Trial Register DRKS00014774 . Registered on 18 May 2018.

Abstract Background Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab. Methods The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if

Abstract Background Despite an initial steep decrease in alcohol misuse among Estonians through structural intervention means and the scaling up of alcohol counselling in the mid-2000’s, most of the country’s alcohol misuse indicators remain clearly higher than European averages. Consequently, an online self-help program was launched as part of an initial behavioral intervention initiative to foster progress in alcohol prevention on a population level. Methods A two-arm randomized controlled trial (RCT) has been designed to compare the efficacy of a culturally-adapted minimal-guidance online self-help program, the 8-week “Selge” online program against a control condition that consists of a self-administered test of alcohol use and advice regarding usual treatment in Estonia. A target sample of 600 individuals will be recruited and randomly assigned to either condition. The program will contain 10 modules based on principles of cognitive behavioural therapy (CBT) and motivational interviewing (MI). Participants in the control group will have access to the full treatment after they complete their final follow-up assessment. The primary outcome will be change in the Alcohol Use Disorders Identification Test (AUDIT) score between the 6-month follow-up and baseline assessments. Secondary outcomes will include the number of standard drinks consumed and alcohol-free days, drinking motives and motivation for change, as well as changes in mental health. Assessments will be completed at baseline, at the end of treatment, and at 6 months follow-up. Data analysis will follow the intention-to-treat principle and employ (generalised) linear mixed models. Discussion The “Selge” program is the first and only internet program for the intervention of alcohol misuse in Estonia. If proven effective, it will foster progress in the intervention of alcohol misuse in the Estonian population and be implemented as a standard program amidst the continuum of intervention and care. Trial registration Current Controlled Trials ISRCTN48753339 registered 04/06/2019 retrospectively.

Abstract Background The System Usability Scale (SUS) is used to measure usability of internet-based Cognitive Behavioural Therapy (iCBT). However, whether the SUS is a valid instrument to measure usability in this context is unclear. The aim of this study is to assess the factor structure of the SUS, measuring usability of iCBT for depression in a sample of professionals. In addition, the psychometric properties (reliability, convergent validity) of the SUS were tested. Methods A sample of 242 professionals using iCBT for depression from 6 European countries completed the SUS. Confirmatory Factor Analysis (CFA) was conducted to test whether a one-factor, two-factor, tone-model or bi-direct model would fit the data best. Reliability was assessed using complementary statistical indices (e.g. omega). To assess convergent validity, the SUS total score was correlated with an adapted Client Satisfaction Questionnaire (CSQ-3). Results CFA supported the one-factor, two-factor and tone-model, but the bi-factor model fitted the data best (Comparative Fit Index = 0.992, Tucker Lewis Index = 0.985, Root Mean Square Error of Approximation = 0.055, Standardized Root Mean Square Residual = 0.042 (respectively χ2 diff (9) = 69.82, p

BackgroundAlthough major depressive disorder (MDD) is characterized by a pervasive negative mood, research indicates that the mood of depressed patients is rarely entirely stagnant. It is often dynamic, distinguished by highs and lows, and it is highly responsive to external and internal regulatory processes. Mood dynamics can be defined as a combination of mood variability (the magnitude of the mood changes) and emotional inertia (the speed of mood shifts). The purpose of this study is to explore various distinctive profiles in real-time monitored mood dynamics among MDD patients in routine mental healthcare.MethodsEcological momentary assessment (EMA) data were collected as part of the cross-European E-COMPARED trial, in which approximately half of the patients were randomly assigned to receive the blended Cognitive Behavioral Therapy (bCBT). In this study a subsample of the bCBT group was included (n = 287). As part of bCBT, patients were prompted to rate their current mood (on a 1–10 scale) using a smartphone-based EMA application. During the first week of treatment, the patients were prompted to rate their mood on three separate occasions during the day. Latent profile analyses were subsequently applied to identify distinct profiles based on average mood, mood variability, and emotional inertia across the monitoring period.ResultsOverall, four profiles were identified, which we labeled as: (1) “very negative and least variable mood” (n = 14) (2) “negative and moderate variable mood” (n = 204), (3) “positive and moderate variable mood” (n = 41), and (4) “negative and highest variable mood” (n = 28). The degree of emotional inertia was virtually identical across the profiles.ConclusionsThe real-time monitoring conducted in the present study provides some preliminary indications of different patterns of both average mood and mood variability among MDD patients in treatment in mental health settings. Such varying patterns were not found for emotional inertia.

Objective: Many young adults struggle with comorbid alcohol misuse and emotional problems (i.e., depression and anxiety). However, there is currently a paucity of evidence-based, integrated, accessible treatment options for individuals with these comorbidities. The main goal of this study was to examine efficacy of a novel online, minimally guided, integrated program for comorbid alcohol misuse and emotional problems in young adults. Method: The study was an open-label two-arm RCT. Participants (N = 222, Mage = 24.6, 67.6% female) were randomized to one of two conditions: the Take Care of Me program (an 8-week, online integrated treatment condition consisting of 12 modules), or an online psychoeducational control condition. Intervention modules incorporated content based on principles of cognitive behavioral therapy and motivational interviewing. Participants completed assessment data at baseline, at the end of treatment (i.e., 8 weeks), and at follow-up (i.e., 24 weeks). Data were analyzed using generalized linear mixed models. Results: We observed that participants in the treatment condition showed larger reductions in depression, hazardous drinking, as well as increases in psychological quality of life and confidence at the end of treatment. We did not find group differences on total alcohol use at follow-up, but participants in the treatment group reduced their hazardous drinking and improved their quality of life at 24-week follow-up. Conclusions: Our study provides promising initial evidence for the first iteration of the comorbid alcohol misuse and emotional problems online program.

Objective: This experiment aims to investigate the influence of narrative information varying in the degree of perceived similarity and source credibility in supplemented testimonials on the acceptance of digital mental health services (digi-MHSs).Methods: In fall 2020, n=231 university students were randomly assigned to an active control group (aCG, n=55, “information only”) or one of three intervention groups (IGs) receiving information plus different testimonials being presented either by nonacademic staff (IG1, n=60), university students (IG2, n=58) or experts (IG3, n=58). We assessed mediation effects of similarity and credibility on acceptance in terms of attitudes and usage intentions.Results: Exposure to testimonials was associated with higher usage intentions (d=0.50) and more positive attitudes toward digi-MHSs (d=0.32) compared to mere information (aCG). Regarding source-related effects, one-way ANOVA showed group differences in intentions (ηp2=0.13) that were significantly higher after exposure to testimonials targeted at students than in the other groups after adjusting for baseline intentions (ηp2=0.24). Concerning underlying mechanisms, there were full mediation effects of similarity (IG1 versus IG2) on attitudes [95%CI (0.030, 0.441)] and intentions to use digi-MHSs [95%CI (0.100, 0.528)] and of credibility on attitudes [IG2 versus IG3; 95%CI (−0.217, −0.004)], all favoring students’ testimonials.Conclusion: Overall, this study indicates that the acceptance of digi-MHSs can be substantially increased by providing a simple, context-sensitive information intervention, including testimonials by university students. Since we identified mediating effects of credibility on cognitive attitudes and similarity on affect-driven intentions, a future trial could vary these features using narrative versus statistic information on digi-MHSs.

Background: The literature shows a high prevalence of depression and anxiety in young people. The university represents a change in the lives of students, and is considered a stress factor. Therefore, it is particularly relevant to develop interventions specifically addressed to students and foster supportive environments and resilient communities. As students are “digital natives”, online interventions offer several potential advantages in doing this. This study aims to develop and evaluate the efficacy of an Internet-based intervention (CORE: Cultivating our Resilience), based on the Ryff model of well-being, to promote resilience and coping skills, decrease symptoms of depression and anxiety, and increase overall wellbeing in young people confronting a crucial life event (the university). This paper summarizes the study protocol. Method: The design of the planned study is a randomized controlled trial. A minimum of 464 participants will be randomly assigned to two conditions: 1) an unguided Internet-based intervention to enhance resilience (N = 232); 2) a care-as-usual condition (CAU) (N = 232). The primary outcome will be the Connor-Davidson resilience scale. Secondary outcomes will – among others - include other relevant clinical measures, such as anxiety and depressive symptoms, quality of life, and social support. Outcomes will be assessed 4 and 8 weeks, and 6 and 12-months follow-ups. Intention-to-treat and per-protocol analyses will be performed. Discussion: The results of this study will contribute to the growing research on Internet-delivered interventions. The expected results may have a major impact on the prevention of mental disorders and possible negative consequences in at-risk populations, such as college students. Keywords: Resilience, Internet intervention, University students, Well-being

Background: Depression and anxiety are highly prevalent and often co-occur. Several studies indicate the potential of disorder-specific psychological interventions for the prevention of each of these disorders. To treat comorbidity, transdiagnostic treatment concepts seem to be a promising approach, however, evidence for transdiagnostic concepts of prevention remains inconclusive. Internet- and mobile-based interventions (IMIs) may be an effective means to deliver psychological interventions on a large scale for the prevention of common mental disorders (CMDs) such as depression and anxiety. IMIs have been shown to be effective in treating CMDs, e.g. in reducing symptoms of depression and anxiety. However, there is a lack of studies examining the efficacy of interventions reducing the incidence of CMDs. Moreover, the comparative cost-effectiveness of guided versus unguided IMIs for the prevention of depression and anxiety has not been studied yet. Hence, this study aims at investigating the (cost-) effectiveness of guided and unguided internet- and mobile-based transdiagnostic individually tailored indicated prevention of depression and anxiety. Methods: A multi-country three-armed randomized controlled trial will be conducted to compare a guided and unguided intervention to treatment as usual (TAU). Both active conditions are based on the same intervention, ICare Prevent, and differ only with regard to guidance format. Altogether, 954 individuals with subclinical symptoms of depression (CES-D ≥ 16) and anxiety (GAD-7 ≥ 5) who do not have a full-blown disorder will be recruited in Germany, Switzerland, Spain and the Netherlands, and randomized to one of three conditions (guided intervention, unguided intervention, or TAU). The TAU arm will receive access to the training after a 12-month waiting period. The primary outcome will be time to CMD onset (any depression/anxiety disorder) within a follow-up period of 12 months after baseline. Secondary outcomes will include disorder-specific symptom severity (depression/anxiety) assessed by diagnostic raters blinded to intervention condition at post-intervention, self-reports, acceptability, health related quality of life, and psychosocial variables associated with developing a CMD. Assessments will take place at baseline, mid-intervention (5 weeks into the intervention), post-intervention (8 weeks after randomization) and follow-up (6 and 12 months after randomization). Data will be analyzed on an intention-to-treat basis and per protocol. Cost-effectiveness will be evaluated from a public health and a societal perspective, including both direct and indirect costs. Discussion: The present study will further enhance the evidence-base for transdiagnostic preventive interventions and provide valuable information about optimal trade-off between treatment outcome and costs. Trial registration: German Clinical Trial Registration (DRKS - http://www.drks.de/drks_web/): DRKS00011099. Keywords: Prevention, Transdiagnostic, Depression, Anxiety, Internet-based, Randomized controlled trial

Abstract Background The rumen wall plays a major role in efficient transfer of digested nutrients in the rumen to peripheral tissues through the portal venous system. Some of these substrates are metabolised in the epithelium during this process. To identify the specific proteins involved in these processes, we used proteomic technologies. Protein extracts were prepared from ventral rumen tissue of six sheep fed a fibrous diet at 1.5× maintenance energy requirements. Using a newly developed method, we were able to enzymatically isolate the epithelial cells from underlying tissue layers, thus allowing cytosol and membrane fractions to be independently analysed using liquid chromatography tandem mass spectrometry (LC MS/MS). Results Using our procedure we identified 570 epithelial proteins in the Ovis aries sequence database. Subcellular locations were largely cytosolic (n = 221) and extracellular (n = 85). However, a quarter of the proteins identified were assigned to the plasma membrane or organelle membranes, some of which transport nutrients and metabolites. Of these 91 were transmembrane proteins (TMHMM), 27 had an N-terminal signal peptide (signalP) and TMHMM motif, 13 had a glycosylphosphatidylinositol (GPI) anchor and signalP sequence, 67 had beta (β) strands or 17 β strands and a transit peptide sequence, indicating the identified proteins were integral or peripheral membrane proteins. Subunits of the 5 protein complexes involved in mitochondrial cellular energy production were well represented. Structural proteins (15%), proteins involved in the metabolism of lipids and proteins (26%) and those with steroid or cytokine action were a feature of the proteome. Conclusion Our research has developed a procedure to isolate rumen epithelium proteins from the underlying tissue layers so that they may be profiled using proteomic technologies. The approach improves the number of proteins that can be profiled that are specific to the epithelium of the rumen wall. It provides new insights into the proteins of structural and nutritional importance in the rumen epithelium, that carry out nutrient transport and metabolism, cell growth and signalling.

Background: Body dysmorphic disorder (BDD) is a relatively common mental disorder in adolescents and young adults, and is characterized by severe negative psychosocial consequences and high comorbidity as well as high mortality rates, mainly due to suicides. While patients in Germany have health insurance-financed access to evidence-based outpatient treatments, that is, cognitive-behavioral treatment (CBT), waiting lists are long. Furthermore, patients with BDD report diverse treatment barriers, primarily feelings of shame and the belief that they would be better off with treatments that would alter the perceived flaw(s). Given adolescents' and young adults' high affinity to electronic media, the accessibility of evidence-based care for this severe mental disorder could be improved by providing an internet-based therapist-guided CBT intervention.Methods: In a two-arm randomized controlled trial (N = 40), adolescents and young adults (15–21 years) with a primary diagnosis of BDD based on a semi-structured clinical expert interview will be randomly allocated to an internet-based therapist-guided CBT intervention or a supportive internet-based therapy intervention. Assessments will take place at baseline, after mid-intervention (after 6 weeks), post-intervention, and at 4-week follow-up. The primary outcome is expert-rated BDD symptom severity at the primary endpoint post-intervention. Secondary outcomes include responder and remission rates based on expert rating, self-reported BDD symptoms, and psychosocial variables associated with BDD.Interventions: The CBT-based intervention consists of six modules each comprising one to three sessions, which focus on psychoeducation, cognitive restructuring, work on self-esteem, exposure and ritual prevention, mirror retraining, and relapse prevention. A study therapist provides feedback after each session. The supportive therapy intervention consists of access to psychoeducational materials for the same 12-week period and at least one weekly supportive interaction with the study therapist.Conclusions: This is the first study to examine the feasibility and efficacy of an internet-based therapist-guided CBT intervention in adolescents and young adults with BDD. It could be an important first step to increase accessibility of care in this age group and for this severe and debilitating mental disorder.Clinical Trial Registration: German Register of Clinical Studies, DRKS00022055.

Since the emergence of psychological interventions delivered via the Internet they have differed in numerous ways. The wealth of formats, methods, and technological solutions has led to increased availability and cost-effectiveness of clinical care, however, it has simultaneously generated a multitude of terms. With this paper, we first aim to establish whether a terminology issue exists in the field of Internet-delivered psychological interventions. If so, we aim to determine its implications for research, education, and practice. Furthermore, we intend to discuss solutions to mitigate the problem; in particular, we propose the concept of a common glossary. We invited 23 experts in the field of Internet-delivered interventions to respond to four questions, and employed the Delphi method to facilitate a discussion. We found that experts overwhelmingly agreed that there were terminological challenges, and that it had significant consequences for conducting research, treating patients, educating students, and informing the general public about Internet-delivered interventions. A cautious agreement has been reached that formulating a common glossary would be beneficial for the field to address the terminology issue. We end with recommendations for the possible formats of the glossary and means to disseminate it in a way that maximizes the probability of broad acceptance for a variety of stakeholders.

The college years are stressful for many students. Identifying the sources of stress and their relative importance in leading to clinically significant emotional problems may assist in the development of targeted stress management interventions. The current report examines the distribution and associations of perceived stress across major life areas with 12-month prevalence of common mental disorders in a cross-national sample of first-year college students. The 20,842 respondents were from 24 universities in 9 countries that participated in the World Health Organization World Mental Health International College Student Initiative. Logistic regression analysis examined associations of current perceived stress in six life areas (financial situation, health, love life, relationships with family, relationships at work/school, problems experienced by loved ones) with six types of 12-month mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder). Population attributable risk proportions (PARPs) were calculated to estimate the upper-bound potential effects of interventions focused on perceived stress in reducing prevalence of mental disorders. The majority of students (93.7%) reported at least some stress in at least one of the six areas. A significant dose-response association was found between extent of stress in each life area and increased odds of at least one of the six disorders. The multivariable models that included all stress measures were significant for all disorders (F = 20.6–70.6, p < 0.001). Interpretation of PARPs as representing causal effects of stresses on disorders suggests that up to 46.9–80.0% of 12-month disorder prevalence might be eliminated if stress prevention interventions were developed to block the associations of stress with these disorders.

BackgroundPrevious studies show that university students experience higher psychological stress than the general population, resulting in increased vulnerability for mental disorders for the student population. Online mindfulness interventions will be delivered to students as a potentially promising and more flexible approach compared to face-to-face interventions with the aim of improving their mental health. This study purposes to investigate the effectiveness of a guided online mindfulness-focused intervention for university students by using both self-reported and psychobiological measures.Methods and analysesIn this multicentre, two-armed randomised controlled trial with a parallel design, a guided version of the online mindfulness-focused intervention ‘StudiCare Mindfulness’ will be compared with a waitlist control group. In total, 120 participants will be recruited at different universities (of Applied Sciences) in (Neu-) Ulm. Data will be assessed prior to randomisation, after eight weeks (post-intervention) and six months after randomisation (follow-up). The primary outcome measure is mindfulness. The secondary outcome measures include depression, anxiety and stress levels, well-being, interoceptive sensibility, emotion regulation and alexithymia. Psychobiological parameters comprise interoceptive accuracy, hair cortisol and FKBP5 genotype. Sociodemographic variables, treatment expectations, side and adverse side effects, as well as intervention satisfaction and adherence will be assessed. All data analyses will be conducted according to the intention-to-treat principle.Ethics and disseminationAll study procedures have been approved by the Ethics Committee of Ulm University (application No. 48/18). The findings will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberDRKS00014701.

Background: Farmers show high levels of depressive symptoms and mental health problems in various studies. This study is part of a nationwide prevention project carried out by a German social insurance company for farmers, foresters, and gardeners (SVLFG) to implement internet- and tele-based services among others to improve mental health in this population. The aim of the present study is to evaluate the (cost-)effectiveness of personalized tele-based coaching for reducing depressive symptom severity and preventing the onset of clinical depression, compared to enhanced treatment as usual.Methods: In a two-armed, pragmatic randomized controlled trial (N = 312) with follow-ups at post-treatment (6 months), 12 and 18 months, insured farmers, foresters, and gardeners, collaborating family members and pensioners with elevated depressive symptoms (PHQ-9 ≥ 5) will be randomly allocated to personalized tele-based coaching or enhanced treatment as usual. The coaching is provided by psychologists and consists of up to 34 tele-based sessions for 25–50 min delivered over 6 months. Primary outcome is depressive symptom severity at post-treatment. Secondary outcomes include depression onset, anxiety, stress, and quality of life. A health-economic evaluation will be conducted from a societal perspective.Discussion: This study is the first pragmatic randomized controlled trial evaluating the (cost-)effectiveness of a nationwide tele-based preventive service for farmers. If proven effective, the implementation of personalized tele-based coaching has the potential to reduce disease burden and health care costs both at an individual and societal level.Clinical Trial Registration: German Clinical Trial Registration: DRKS00015655.

Purpose. The workup and surveillance strategies for infant hydronephrosis (HN) vary, although this could be due to grade-dependent differences in imaging intensity. We aimed to describe the frequency of imaging studies for HN within the first year of life, stratified by initial HN grade, within a large regional healthcare system. Study Design and Data Source. Retrospective cohort using Intermountain Healthcare Data Warehouse. Inclusion criteria: (1) birth between 1/1/2005 and 12/31/2013, (2) CPT code for HN, and (3) ultrasound (U/S) confirmed HN within four months of birth. Data Collection. Grade of HN on initial postnatal U/S; number of HN-associated radiologic studies (renal U/Ss, voiding cystourethrograms (VCUGs), and diuretic renal scans); demographic and medical variables. Primary Outcome. Sum of radiologic studies within the first year of life or prior to pyeloplasty. Statistical Analysis. Multivariate poisson regression to analyze association between the primary outcome and the initial HN grade. Results. Of 1,380 subjects (993 males and 387 females), 990 (72%), 230 (17%), and 160 (12%) had mild, moderate, and severe HN, respectively. Compared with those with mild HN, patients with moderate (RR: 1.57; 95% CI: 1.42–1.73) and severe (RR: 2.09; 95% CI: 1.88–2.32) HN had a significantly higher rate of imaging use over 12 months (or prior to surgery) after controlling for potential confounders. Conclusions. In a large regional healthcare system, imaging use for HN is proportional to its initial grade. This suggests that within our system, clinicians treating this condition are using a risk-stratified approach to imaging.

Abstract Background Depression and anxiety are common and co-morbid disorders that affect a significant proportion of students. Innovative prevention strategies targeting both conditions are needed to reduce their health burden and costs. ICare Prevent is such an innovative strategy and contains a transdiagnostic individually tailored Internet-based and mobile-supported intervention. It addresses common risk factors of depression and anxiety as part of a large EU-funded multi-country project* (ICare). Little is known about the clinical and cost-effectiveness of this type of intervention compared to care as usual (CAU) for college students. We hypothesize that ICare Prevent will be more (cost-)effective than CAU in the reduction of symptoms of depression and anxiety. Methods A three-arm, parallel, randomized controlled superiority trial will be conducted comparing a guided and an unguided version of ICare Prevent with a control group receiving CAU. The trial will be open-label but outcome assessors will be blinded. A total of 252 college students (age ≥ 16 years) with subclinical symptoms of depression defined as a score ≥ 16 on the Center for Epidemiological Studies Depression Scale (CES-D), and/or anxiety, defined as a score ≥ 5 on the Generalized Anxiety Disorder scale (GAD-7), will be included. Those meeting diagnostic criteria for a depressive or anxiety disorder will be excluded. The primary outcome is change in disorder specific symptom severity from baseline to post-intervention. Secondary endpoints include self-reported depression and anxiety symptoms as well as time to onset of a mood or anxiety disorder until 12-month follow-up. Societal costs and quality of life will be assessed to estimate the intervention’s cost-effectiveness compared to CAU. Discussion Transdiagnostic individually tailored Internet-based prevention could be a (cost-)effective approach to tackle the disease burden of depression and anxiety among college students. Trial registration Dutch trial register, NTR 6562. Registered on 6 July 2017.