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Stress has been identified as one of the major public health issues in this century. New technologies offer opportunities to provide effective psychological interventions on a large scale. The aim of this study is to investigate the efficacy of Web- and computer-based stress-management interventions in adults relative to a control group. A meta-analysis was performed, including 26 comparisons (n=4226). Cohen d was calculated for the primary outcome level of stress to determine the difference between the intervention and control groups at posttest. Analyses of the effect on depression, anxiety, and stress in the following subgroups were also conducted: risk of bias, theoretical basis, guidance, and length of the intervention. Available follow-up data (1-3 months, 4-6 months) were assessed for the primary outcome stress. The overall mean effect size for stress at posttest was Cohen d=0.43 (95% CI 0.31-0.54). Significant, small effects were found for depression (Cohen d=0.34, 95% CI 0.21-0.48) and anxiety (Cohen d=0.32, 95% CI 0.17-0.47). Subgroup analyses revealed that guided interventions (Cohen d=0.64, 95% CI 0.50-0.79) were more effective than unguided interventions (Cohen d=0.33, 95% CI 0.20-0.46; P=.002). With regard to the length of the intervention, short interventions (≤4 weeks) showed a small effect size (Cohen d=0.33, 95% CI 0.22-0.44) and medium-long interventions (5-8 weeks) were moderately effective (Cohen d=0.59; 95% CI 0.45-0.74), whereas long interventions (≥9 weeks) produced a nonsignificant effect (Cohen d=0.21, 95% CI -0.05 to 0.47; P=.006). In terms of treatment type, interventions based on cognitive behavioral therapy (CBT) and third-wave CBT (TWC) showed small-to-moderate effect sizes (CBT: Cohen d=0.40, 95% CI 0.19-0.61; TWC: Cohen d=0.53, 95% CI 0.35-0.71), and alternative interventions produced a small effect size (Cohen d=0.24, 95% CI 0.12-0.36; P=.03). Early evidence on follow-up data indicates that Web- and computer-based stress-management interventions can sustain their effects in terms of stress reduction in a small-to-moderate range up to 6 months. These results provide evidence that Web- and computer-based stress-management interventions can be effective and have the potential to reduce stress-related mental health problems on a large scale.

Introduction. Diabetes mellitus type 1 and type 2 are linked to higher prevalence and occurrences of depression. Internet-based depression- and diabetes-specific cognitive behavioral therapies (CBT) can be effective in reducing depressive symptom severity and diabetes-related emotional distress. The aim of the study was to test whether disease-specific severity indicators moderate the treatment outcome in a 6-week minimally guided web-based self-help intervention on depression and diabetes (GET.ON Mood Enhancer Diabetes (GET.ON M.E.D.)) and to determine its effectiveness in a nonsuicidal severely depressed subgroup. Methods. Randomized controlled trial- (RCT-) based data (N=253) comparing GET.ON M.E.D. to an online psychoeducation control group was used to test disease-specific severity indicators as predictors/moderators of a treatment outcome. Changes in depressive symptom severity and treatment response were examined in a nonsuicidal severely depressed subgroup (CES−D>40; N=40). Results. Major depressive disorder diagnosis at the baseline (pprf6=0.01), higher levels of depression (Beck Depression Inventory II; pprpo=0.00; pprf6=0.00), and lower HbA1c (pprpo=0.04) predicted changes in depressive symptoms. No severity indicator moderated the treatment outcome. Severely depressed participants in the intervention group showed a significantly greater reduction in depressive symptom severity (dprpo=2.17, 95% Confidence Interval (CI): 1.39-2.96) than the control condition (dprpo=0.92; 95% CI: 0.001-1.83), with a between-group effect size of dprpo=1.05 (95% CI: 0.11-1.98). Treatment response was seen in significantly more participants in the intervention (4/20; 20%) compared to the control group (0/20, 0%; χ2 2N=40=4.44; p<0.02). At the 6-month follow-up, effects were maintained for depressive symptom reduction (dpr6f=0.71; 95% CI: 0.19-1.61) but not treatment response. Conclusion. Disease-specific severity indicators were not related to a differential effectiveness of guided self-help for depression and diabetes. Clinical meaningful effects were observed in nonsuicidal severely depressed individuals, who do not need to be excluded from web-based guided self-help. However, participants should be closely monitored and referred to other treatment modalities in case of nonresponse.

Abstract Study Objectives: Lost productivity caused by insomnia is a common and costly problem for employers. Although evidence for the efficacy of Internet-based cognitive behavioral therapy for insomnia (iCBT-I) already exists, little is known about its economic effects. This study aims to evaluate the cost-effectiveness and cost-benefit of providing iCBT-I to symptomatic employees from the employer's perspective. Methods: School teachers (N = 128) with clinically significant insomnia symptoms and work-related rumination were randomized to guided iCBT-I or a waitlist-control-group, both with access to treatment as usual. Economic data were collected at baseline and 6-mo follow-up. We conducted (1) a cost-effectiveness analysis with treatment response (Reliable Change [decline of 5.01 points] and Insomnia Severity Index < 8 at 6-month follow-up) as the outcome and (2) a cost-benefit analysis. Because both analyses were performed from the employer's perspective, we focused specifically on absenteeism and presenteeism costs. Statistical uncertainty was estimated using bootstrapping. Results: Assuming intervention costs of €200 ($245), cost-effectiveness analyses showed that at a willingness-to-pay of €0 for each positive treatment response, there is an 87% probability that the intervention is more cost effective than treatment as usual alone. Cost-benefit analyses led to a net benefit of €418 (95% confidence interval: −593.03 to 1,488.70) ($512) per participant and a return on investment of 208% (95% confidence interval: −296.52 to 744.35). The reduction in costs was mainly driven by the effects of the intervention on presenteeism and to a lesser degree by reduced absenteeism. Conclusions: Focusing on sleep improvement using iCBT-I may be a cost-effective strategy in occupational health care. Clinical Trials Registration: Title: Online Recovery Training for Better Sleep in Teachers with High Psychological Strain. German Clinical Trial Register (DRKS), URL: https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004700. Identifier: DRKS00004700. Commentary: A commentary on this article appears in this issue on page 1767.

Introduction: Evidence on effects of Internet-based interventions to treat subthreshold depression (sD) and prevent the onset of major depression (MDD) is inconsistent. Objective: We conducted an individual participant data meta-analysis to determine differences between intervention and control groups (IG, CG) in depressive symptom severity (DSS), treatment response, close to symptom-free status, symptom deterioration and MDD onset as well as moderators of intervention outcomes. Methods: Randomized controlled trials were identified through systematic searches via PubMed, PsycINFO, Embase and Cochrane Library. Multilevel regression analyses were used to examine efficacy and moderators. Results: Seven trials (2,186 participants) were included. The IG was superior in DSS at all measurement points (posttreatment: 6–12 weeks; Hedges’ g = 0.39 [95% CI: 0.25–0.53]; follow-up 1: 3–6 months; g = 0.30 [95% CI: 0.15–0.45]; follow-up 2: 12 months, g = 0.27 [95% CI: 0.07–0.47], compared with the CG. Significantly more participants in the IG than in the CG reached response and close to symptom-free status at all measurement points. A significant difference in symptom deterioration between the groups was found at the posttreatment assessment and follow-up 2. Incidence rates for MDD onset within 12 months were lower in the IG (19%) than in the CG (26%). Higher initial DSS and older age were identified as moderators of intervention effect on DSS. Conclusions: Our findings provide evidence for Internet-based interventions to be a suitable low-threshold intervention to treat individuals with sD and to reduce the incidence of MDD. This might be particularly true for older people with a substantial symptom burden.

Psychological interventions for the prevention of depression might be a cost-effective way to reduce the burden associated with depressive disorders. To evaluate the cost-effectiveness of a Web-based guided self-help intervention to prevent major depressive disorder (MDD) in people with subthreshold depression (sD). A pragmatic randomized controlled trial was conducted with follow-up at 12 months. Participants were recruited from the general population via a large statutory health insurance company and an open access website. Participants were randomized to a Web-based guided self-help intervention (ie, cognitive-behavioral therapy and problem-solving therapy assisted by supervised graduate students or health care professionals) in addition to usual care or to usual care supplemented with Web-based psycho-education (enhanced usual care). Depression-free years (DFYs) were assessed by blinded diagnostic raters using the telephone-administered Structured Clinical Interview for DSM-IV Axis Disorders at 6- and 12-month follow-up, covering the period to the previous assessment. Costs were self-assessed through a questionnaire. Costs measured from a societal and health care perspective were related to DFYs and quality-adjusted life years (QALYs). In total, 406 participants were enrolled in the trial. The mean treatment duration was 5.84 (SD 4.37) weeks. On average, participants completed 4.93 of 6 sessions. Significantly more DFYs were gained in the intervention group (0.82 vs 0.70). Likewise, QALY health gains were in favor of the intervention, but only statistically significant when measured with the more sensitive SF-6D. The incremental per-participant costs were €136 (£116). Taking the health care perspective and assuming a willingness-to-pay of €20,000 (£17,000), the intervention's likelihood of being cost-effective was 99% for gaining a DFY and 64% or 99% for gaining an EQ-5D or a SF-6D QALY. Our study supports guidelines recommending Web-based treatment for sD and adds that this not only restores health in people with sD, but additionally reduces the risk of developing a MDD. Offering the intervention has an acceptable likelihood of being more cost-effective than enhanced usual care and could therefore reach community members on a wider scale. German Clinical Trials Register: DRKS00004709; http://www.drks.de/DRKS00004709 (Archived by WebCite at http://www.webcitation.org/6kAZVUxy9).

Web-based interventions are effective in reducing depression. However, the evidence for the cost-effectiveness of these interventions is scarce.AimsThe aim is to assess the cost-effectiveness of a web-based intervention (GET.ON M.E.D.) for individuals with diabetes and comorbid depression compared with an active control group receiving web-based psychoeducation. We conducted a cost-effectiveness analysis with treatment response as the outcome and a cost-utility analysis with quality-adjusted life-years (QALYs) alongside a randomised controlled trial with 260 participants. At a willingness-to-pay ceiling of €5000 for a treatment response, the intervention has a 97% probability of being regarded as cost-effective compared with the active control group. If society is willing to pay €14 000 for an additional QALY, the intervention has a 51% probability of being cost-effective. This web-based intervention for individuals with diabetes and comorbid depression demonstrated a high probability of being cost-effective compared with an active control group.Declaration of interestS.N., D.D.E., D.L., M.B. and B.F. are stakeholders of the Institute for Online Health Trainings, which aims to transfer scientific knowledge related to this research into routine healthcare.

Background Work-related stress is associated with a variety of mental and emotional problems and can lead to substantial economic costs due to lost productivity, absenteeism or the inability to work. There is a considerable amount of evidence on the effectiveness of traditional face-to-face stress-management interventions for employees; however, they are often costly, time-consuming, and characterized by a high access threshold. Web-based interventions may overcome some of these problems yet the evidence in this field is scarce. This paper describes the protocol for a study that will examine the efficacy and cost-effectiveness of a web-based guided stress-management training which is based on problem solving and emotion regulation and aimed at reducing stress in adult employees. Methods The study will target stressed employees aged 18 and older. A randomized controlled trial (RCT) design will be applied. Based on a power calculation of d=.35 (1-β of 80%, α = .05), 264 participants will be recruited and randomly assigned to either the intervention group or a six-month waitlist control group. Inclusion criteria include an elevated stress level (Cohen’s Perceived Stress Scale-10 ≥ 22) and current employment. Exclusion criteria include risk of suicide or previously diagnosed psychosis or dissociative symptoms. The primary outcome will be perceived stress, and secondary outcomes include depression and anxiety. Data will be collected at baseline and seven weeks and six months after randomization. An extended follow up at 12 months is planned for the intervention group. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective and will include both direct and indirect health care costs. Data will be analyzed on an intention-to-treat basis and per protocol. Discussion The substantial negative consequences of work-related stress emphasize the necessity for effective stress-management trainings. If the proposed internet intervention proves to be (cost-) effective, a preventative, economical stress-management tool will be conceivable. The strengths and limitations of the present study are discussed. Trial registration German Register of Clinical Studies (DRKS): DRKS00004749

Background A diagnosis of diabetes mellitus types 1 or 2 doubles the odds of a comorbid depressive disorder. The combined diseases have a wide range of adverse outcomes, such as a lower quality of life, poorer diabetes outcomes and increased healthcare utilisation. Diabetes patients with depression can be treated effectively with psychotherapy, but access to psychological care is limited. In this study we will examine the efficacy and cost-effectiveness of a newly developed web-based intervention (GET.ON Mood Enhancer Diabetes) for people with diabetes and comorbid depressive symptoms. Methods/Design A two-arm randomised controlled trial will be conducted. Adults with diabetes (type 1 or type 2) with increased depression scores (> 22 on the German version of the Center for Epidemiological Studies Depression Scale (CES-D)) will be included. Eligible participants will be recruited through advertisement in diabetes patient journals and via a large-scale German health insurance company. The participants will be randomly assigned to either a 6-week minimally guided web-based self-help program or an online psychoeducation program on depression. The study will include 260 participants, which will enable us to detect a statistically significant difference with a group effect size of d = 0.35 at a power of 80% and a significance level of p = 0.05. The primary outcome measure will be the level of depression as assessed by the CES-D. The secondary outcome measures will be: diabetes-specific emotional distress, glycaemic control, self-management behaviour and the participants’ satisfaction with the intervention. Online self-assessments will be collected at baseline and after a 2 months period, with additional follow-up measurements 6 and 12 months after randomisation. The data will be analysed on an intention-to-treat basis and per protocol. In addition, we will conduct an economic evaluation from a societal perspective. Discussion If this intervention is shown to be cost-effective, it has considerable potential for implementing psychological care for large numbers of people with diabetes and comorbid depression in routine practice and improve health outcomes. Trial registration German Clinical Trial Register (DRKS): DRKS00004748 .

IntroductionDepression often co-occurs with chronic back pain (CBP). Internet and mobile-based interventions (IMIs) might be a promising approach for effectively treating depression in this patient group. In the present study, we will evaluate the effectiveness and cost-effectiveness of a guided depression IMI for individuals with CBP (eSano BackCare-D) integrated into orthopaedic healthcare.Methods and analysisIn this multicentre randomised controlled trial of parallel design, the groups eSano BackCare-D versus treatment as usual will be compared. 210 participants with CBP and diagnosed depression will be recruited subsequent to orthopaedic rehabilitation care. Assessments will be conducted prior to randomisation and 9 weeks (post-treatment) and 6 months after randomisation. The primary outcome is depression severity (Hamilton Rating Scale for Depression-17). Secondary outcomes are depression remission and response, health-related quality of life, pain intensity, pain-related disability, self-efficacy and work capacity. Demographic and medical variables as well as internet affinity, intervention adherence, intervention satisfaction and negative effects will also be assessed. Data will be analysed on an intention-to-treat basis with additional per-protocol analyses. Moreover, a cost-effectiveness and cost-utility analysis will be conducted from a societal perspective after 6 months.Ethics and disseminationAll procedures are approved by the ethics committee of the Albert-Ludwigs-University of Freiburg and the data security committee of the German Pension Insurance (Deutsche Rentenversicherung). The results will be published in peer-reviewed journals and presented on international conferences.Trial registration number DRKS00009272; Pre-results.

Influenza A viruses (IAVs) remain a significant global health burden. Activation of the innate immune response is important for controlling early virus replication and spread. It is unclear how early IAV replication events contribute to immune detection. Additionally, while many cell types in the lung can be infected, it is not known if all cell types contribute equally to establish the antiviral state in the host. Here, we use single-cycle influenza A viruses (scIAVs) to characterize the early immune response to IAV in vitro and in vivo. We found that the magnitude of virus replication contributes to antiviral gene expression within infected cells prior to the induction of a global response. We also developed a scIAV that is only capable of undergoing primary transcription, the earliest stage of virus replication. Using this tool, we uncovered replication stage-specific responses in vitro and in vivo. Using several innate immune receptor knockout cell lines, we identify RIG-I as the predominant antiviral detector of primary virus transcription and amplified replication in vitro. Through a Cre-inducible reporter mouse, we used scIAVs expressing Cre-recombinase to characterize cell type-specific responses in vivo. Individual cell types upregulate unique sets of antiviral genes in response to both primary virus transcription and amplified replication. We also identified antiviral genes that are only upregulated in response to direct infection. Altogether, these data offer insight into the early mechanisms of antiviral gene activation during influenza A infection.