Substantial transmission of SARS-CoV-2 through casual contact in retail stores: Evidence from matched administrative microdata on card payments and testing.

This paper presents quasiexperimental evidence of Covid-19 transmission through casual contact between customers in retail stores. For a large sample of individuals in Denmark, we match card payment data, indicating exactly where and when each individual made purchases, with Covid-19 test data, indicating when each individual was tested and whether the test was positive. The resulting dataset identifies more than 100,000 instances where an infected individual made a purchase in a store and, in each instance, allows us to track the infection dynamics of other individuals who made purchases in the same store around the same time. We estimate transmissions by comparing the infection rate of exposed customers, who made a purchase within 5 min of an infected individual, and nonexposed customers, who made a purchase in the same store 16 to 30 min before. We find that exposure to an infected individual in a store increases the infection rate by around 0.12 percentage points (P < 0.001) between day 3 and day 7 after exposure. The estimates imply that transmissions in stores contributed around 0.04 to the reproduction number for the average infected individual and significantly more in the period where Omicron was the dominant variant.

The long shadow of early-change patterns: a 3-year follow-up after the use of a web-based intervention for mild to moderate depressive symptoms.

Web-based interventions can be effective in treating depressive symptoms. Patients with risk not responding to treatment have been identified by early change patterns. This study aims to examine whether early changes are superior to baseline parameters in predicting long-term outcome. In a randomized clinical trial with 409 individuals experiencing mild to moderate depressive symptoms using the web-based intervention deprexis, three latent classes were identified (early response after registration, early response after screening and early deterioration) based on early change in the first four weeks of the intervention. Baseline variables and these classes were included in a Stepwise Cox Proportional Hazard Multiple Regression to identify predictors associated with the onset of remission over 36-months. Early change class was a significant predictor of remission over 36 months. Compared to early deterioration after screening, both early response after registration and after screening were associated with a higher likelihood of remission. In sensitivity and secondary analyses, only change class consistently emerged as a predictor of long-term outcome. Early improvement in depression symptoms predicted long-term outcome and those showing early improvement had a higher likelihood of long-term remission. These findings suggest that early changes might be a robust predictor for long-term outcome beyond baseline parameters.

Mobile health interventions in multiple sclerosis: A systematic review.

BACKGROUND: Persons with multiple sclerosis (pwMS) might be particularly well suited to benefit from digital health applications because they are, on average, younger and less severely disabled than patients with many other chronic diseases. Many digital health applications for pwMS have been developed. OBJECTIVES: Analysis of the evidence of digital health applications to improve health outcomes from a patient perspective. METHODS: A systematic review was performed on all randomized controlled trials (RCTs) that have studied mobile health interventions for pwMS, that is, which can be applied with a smartphone, tablet, or laptop to improve patient-reported outcomes. RESULTS: Of the 1127 articles identified in the literature search, 13 RCTs fit the inclusion criteria. Two trials studied messaging systems, two depression interventions, one addressed MS fatigue, five cognition, and three mobility issues, of which two focused on spasticity management. One trial aimed to enhance physical activity. Most were pilot studies that cannot yield definitive conclusions regarding efficacy. One depression intervention and one fatigue intervention showed significant results across several outcomes. CONCLUSION: Several mobile self-guided digital health applications for pwMS have been tested in RCTs, and two interventions targeting depression and fatigue have demonstrated significant effects. Challenges remain regarding implementation into routine care.

Acceptability of a digital health application to empower persons with multiple sclerosis with moderate to severe disability: single-arm prospective pilot study.

BACKGROUND: Many persons with multiple sclerosis (pwMS) desire to learn how health behaviour changes (e.g., dietary adjustments, physical activity, improvements in stress management) might help them manage their disease. Previous research has shown that certain health behaviour changes can improve quality of life (QoL), fatigue and other MS outcomes. Digital health applications may be well suited to deliver relevant health behavioural interventions because of their accessibility and flexibility. The digital health application "levidex" was designed to facilitate health behaviour change by offering evidence-based patient information and cognitive-behavioural therapy techniques to pwMS. By doing so, levidex aims to improve QoL and MS symptoms such as fatigue and mental health. OBJECTIVES: A previous study reported on the development of levidex; this non-randomised pilot study examined the feasibility (practicability and acceptability) of levidex in pwMS with moderate to severe disability. Furthermore, the intervention's impact on empowerment, stress management, and relevant health behaviours (e.g., dietary behaviour, physical activity) was explored. METHODS: levidex was originally developed for newly diagnosed pwMS in the first year after diagnosis and eventually modified to offer access to pwMS with moderate to severe disability. Participants (n = 43) with an Expanded Disability Status Scale between 3.5 and 7.5 and a disease duration of more than one year were eligible to participate. The intervention was used over a period of six months with measurement time points at baseline, month 3 and month 6. RESULTS: Out of 38 participants who completed the six-month intervention period, 18 (47.4%) completed all 16 modules and 9 (23.7%) reached modules 13-16, the long-term maintenance part of levidex. Participants rated levidex positively in terms of practicability and acceptability and had only few points of criticism such as to include more physical exercise routine suggestions suitable for participants with severe impairment. Data on secondary endpoints showed no significant changes. CONCLUSION: This pilot study provided evidence for the practicability and acceptability of levidex, a digital health application designed to facilitate health behaviour change in pwMS with moderate to severe disability. Adequately powered randomised controlled studies with longer follow-up periods are needed to clarify the benefit of levidex in pwMS with moderate to severe disability. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00032667 (14/09/2023); Retrospectively registered.

A protocol for a multicentre, parallel-group, pragmatic randomised controlled trial to evaluate the NEVERMIND system in preventing and treating depression in patients with severe somatic conditions.

BACKGROUND: Depressive symptoms are common in individuals suffering from severe somatic conditions. There is a lack of interventions and evidence-based interventions aiming to reduce depressive symptoms in patients with severe somatic conditions. The aim of the NEVERMIND project is to address these issues and provide evidence by testing the NEVERMIND system, designed to reduce and prevent depressive symptoms in comparison to treatment as usual. METHODS: The NEVERMIND study is a parallel-groups, pragmatic randomised controlled trial to assess the effectiveness of the NEVERMIND system in reducing depressive symptoms among individuals with severe somatic conditions. The NEVERMIND system comprises a smart shirt and a user interface, in the form of a mobile application. The system is a real-time decision support system, aiming to predict the severity and onset of depressive symptoms by modelling the well-being condition of patients based on physiological data, body movement, and the recurrence of social interactions. The study includes 330 patients who have a diagnosis of myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants are randomised in blocks of ten to either the NEVERMIND intervention or treatment as usual as the control group. Clinical interviews and structured questionnaires are administered at baseline, at 12 weeks, and 24 weeks to assess whether the NEVERMIND system is superior to treatment as usual. The endpoint of primary interest is Beck Depression Inventory II (BDI-II) at 12 weeks defined as (i) the severity of depressive symptoms as measured by the BDI-II. Secondary outcomes include prevention of the onset of depressive symptoms, changes in quality of life, perceived stigma, and self-efficacy. DISCUSSION: There is a lack of evidence-based interventions aiming to reduce and prevent depressive symptoms in patients with severe somatic conditions. If the NEVERMIND system is effective, it will provide healthcare systems with a novel and innovative method to attend to depressive symptoms in patients with severe somatic conditions. TRIAL REGISTRATION: DRKS00013391. Registered 23 November 2017.

The Association of Therapeutic Alliance With Long-Term Outcome in a Guided Internet Intervention for Depression: Secondary Analysis From a Randomized Control Trial.

BACKGROUND: Therapeutic alliance has been well established as a robust predictor of face-to-face psychotherapy outcomes. Although initial evidence positioned alliance as a relevant predictor of internet intervention success, some conceptual and methodological concerns were raised regarding the methods and instruments used to measure the alliance in internet interventions and its association with outcomes. OBJECTIVE: The aim of this study was to explore the alliance-outcome association in a guided internet intervention using a measure of alliance especially developed for and adapted to guided internet interventions, showing evidence of good psychometric properties. METHODS: A sample of 223 adult participants with moderate depression received an internet intervention (ie, Deprexis) and email support. They completed the Working Alliance Inventory for Guided Internet Intervention (WAI-I) and a measure of treatment satisfaction at treatment termination and measures of depression severity and well-being at termination and 3- and 9-month follow-ups. For data analysis, we used two-level hierarchical linear modeling that included two subscales of the WAI-I (ie, tasks and goals agreement with the program and bond with the supporting therapist) as predictors of the estimated values of the outcome variables at the end of follow-up and their rate of change during the follow-up period. The same models were also used controlling for the effect of patient satisfaction with treatment. RESULTS: We found significant effects of the tasks and goals subscale of the WAI-I on the estimated values of residual depressive symptoms (γ02=-1.74, standard error [SE]=0.40, 95% CI -2.52 to -0.96, t206=-4.37, P<.001) and patient well-being (γ02=3.10, SE=1.14, 95% CI 0.87-5.33, t198=2.72, P=.007) at the end of follow-up. A greater score in this subscale was related to lower levels of residual depressive symptoms and a higher level of well-being. However, there were no significant effects of the tasks and goals subscale on the rate of change in these variables during follow-up (depressive symptoms, P=.48; patient well-being, P=.26). The effects of the bond subscale were also nonsignificant when predicting the estimated values of depressive symptoms and well-being at the end of follow-up and the rate of change during that period (depressive symptoms, P=.08; patient well-being, P=.68). CONCLUSIONS: The results of this study point out the importance of attuning internet interventions to patients' expectations and preferences in order to enhance their agreement with the tasks and goals of the treatment. Thus, the results support the notion that responsiveness to a patient's individual needs is crucial also in internet interventions. Nevertheless, these findings need to be replicated to establish if they can be generalized to different diagnostic groups, internet interventions, and supporting formats.

Identifying change-dropout patterns during an Internet-based intervention for depression by applying the Muthen-Roy model.

To date, only few studies have attempted to investigate non-ignorable dropout during Internet-based interventions by applying an NMAR model, which includes missing data indicators in its equations. Here, the Muthen-Roy model was used to investigate change and dropout patterns in a sample of patients with mild-to-moderate depression symptoms (N = 483) who were randomized to a 12-week Internet-based intervention (deprexis, identifier: NCT01636752). Participants completed the PHQ-9 biweekly during the treatment. We identified four change-dropout patterns: Participants showing high impairment, improvement and low dropout probability (C3, N = 134) had the highest rate of reliable change at 6- and 12-month follow-up. A further pattern was characterized by high impairment, deterioration and high dropout probability (C2, N = 32), another by low impairment, improvement and high dropout probability (C1, N = 198). The last pattern was characterized by high impairment, no change and low dropout probability (C4, N = 119). In addition to deterioration, also rapid improvement may lead to dropout as a result of a perceived "good enough" dosage of treatment. This knowledge may strengthen sensitivity for the mechanisms of dropout and help to consider its meaning in efforts to optimize treatment selection.

The Working Alliance Inventory for guided Internet interventions (WAI-I).

OBJECTIVE: This study analyses the psychometric properties of the Working Alliance Inventory adapted for guided Internet interventions (WAI-I). METHODS: We drew on the data set from a multicenter trial that examined a guided Internet intervention (deprexis) for patients with mild to moderate depression. Two hundred twenty-three patients completed the WAI-I and the Patient Satisfaction Questionnaire (ZUF-8) at posttreatment, and the Attitudes toward Psychological Online-Interventions Questionnaire (APOI) at baseline. We ran confirmatory factor analyses (CFA) testing two- and three-factor solutions and calculated Cronbach's α, item-total correlations, and correlations of the WAI-I with APOI and ZUF-8. RESULTS: The results suggested a two-factor solution, with a very good model fit and evidence of factor independency, adequate internal consistency, and external validity for the complete scale and the sub-scales. CONCLUSIONS: The WAI-I showed as a reliable and valid instrument to capture alliance in guided Internet interventions, which might facilitate process-outcome research and treatment development efforts.

A machine learning ensemble to predict treatment outcomes following an Internet intervention for depression.

BACKGROUND: Some Internet interventions are regarded as effective treatments for adult depression, but less is known about who responds to this form of treatment. METHOD: An elastic net and random forest were trained to predict depression symptoms and related disability after an 8-week course of an Internet intervention, Deprexis, involving adults (N = 283) from across the USA. Candidate predictors included psychopathology, demographics, treatment expectancies, treatment usage, and environmental context obtained from population databases. Model performance was evaluated using predictive R2$\lpar R_{{\rm pred}}^2\rpar\comma $ the expected variance explained in a new sample, estimated by 10 repetitions of 10-fold cross-validation. RESULTS: An ensemble model was created by averaging the predictions of the elastic net and random forest. Model performance was compared with a benchmark linear autoregressive model that predicted each outcome using only its baseline. The ensemble predicted more variance in post-treatment depression (8.0% gain, 95% CI 0.8-15; total $R_{{\rm pred}}^2 \; $= 0.25), disability (5.0% gain, 95% CI -0.3 to 10; total $R_{{\rm pred}}^2 \; $= 0.25), and well-being (11.6% gain, 95% CI 4.9-19; total $R_{{\rm pred}}^2 \; $= 0.29) than the benchmark model. Important predictors included comorbid psychopathology, particularly total psychopathology and dysthymia, low symptom-related disability, treatment credibility, lower access to therapists, and time spent using certain Deprexis modules. CONCLUSION: A number of variables predict symptom improvement following an Internet intervention, but each of these variables makes relatively small contributions. Machine learning ensembles may be a promising statistical approach for identifying the cumulative contribution of many weak predictors to psychosocial depression treatment response.

Effects of an epilepsy-specific Internet intervention (Emyna) on depression: Results of the ENCODE randomized controlled trial.

OBJECTIVE: Depression and anxiety are highly prevalent among people with epilepsy (PwE) but often remain unrecognized and treated inadequately. Effective psychosocial treatments such as cognitive behavioral therapy (CBT) are rarely available to most PwE, which is one reason electronically delivered CBT (eCBT) is regarded as promising. This study examined an eCBT intervention, termed Emyna, that was tailored to suit the needs of PwE. It includes CBT-related content on depression, stress and anxiety, seizure triggers and auras, and lifestyle habits. The trial examined the efficacy of Emyna in reducing symptoms of depression (primary outcome) and anxiety as well as improving quality of life. METHODS: Participants (N = 200) with epilepsy, a diagnosis of a depressive disorder, and at least moderate depressive symptoms were randomized to Emyna or care as usual. At baseline and after 3, 6, and 9 months, participants were invited to complete online questionnaires. The primary outcome was improvement of depressive symptoms at 3 months. RESULTS: Relative to the control group, intervention group participants experienced significantly greater improvements in depression, anxiety, stress, social-occupational impairment, and epilepsy-related quality of life, in both intention-to-treat (ITT) and per-protocol analyses. In ITT analyses, effects of medium magnitude were observed, as measured by the Patient Health Questionnaire-9 items (Cohen d = 0.54, 95% confidence interval [CI] = 0.25-0.82, P < 0.001) and the Neurological Disorders Depression Inventory for Epilepsy (d = 0.51, 95% CI = 0.23-0.79, P < 0.01). At 3 months, intervention group participants also reported fewer illness-related days off work and fewer days hospitalized over the preceding months, compared to control group participants (P ≤ 0.05), whereas no such differences were present at baseline (P > 0.30). SIGNIFICANCE: These findings showed that Emyna, used adjunctively to usual care, could help improve mental health, social-occupational functioning, and quality of life among PwE. The program provides an additional treatment option that could produce clinically relevant symptom reductions and reduce key cost drivers (ie, hospitalization rates and illness-related inability to work).

A patient post hoc perspective on advantages and disadvantages of blended cognitive behaviour therapy for depression: A qualitative content analysis.

Background: Blended cognitive behavioural therapy (bCBT), which combines face-to-face (FtF), and internet-based cognitive behavioural therapy (iCBT), may be a particularly promising approach, but little is known about the effectiveness and patients' subjective evaluations of the bCBT format. The aim of this qualitative study is to explore perceived advantages and disadvantages of bCBT from the patients' perspective in specialized mental health care. Methods: Semi-structured interviews were conducted with 15 patients suffering from major depression who underwent treatment in a bCBT format. The interview data were processed by means of a qualitative content analysis. Results: The content analysis generated 18 advantages and 15 disadvantages which were grouped into 6 main topics. In general, bCBT was perceived as purposive and effective for treating depression. The patients perceived the combined treatment as complementary and emphasized the advantage of the constant availability of the online programme. Furthermore, a segment analysis revealed that patients reported different advantages and disadvantages of bCBT as a function of the severity of their depressive episode. Conclusion: The findings of the present study reveal advantages and disadvantages of bCBT, which should be taken into account in the further implementation of this new treatment format. Clinical or methodological significance of this article: Blended treatment seems to balance missing aspects of stand-alone internet-based and face-to-face treatment for depression. Patients suffering from major depression perceived the blended format as purposive and effective after 18 weeks. Patients with different levels of depression severity may perceive different advantages and disadvantages of blended treatment for depression.

Identification and characterization two isoforms of NADH:ubiquinone oxidoreductase from the hyperthermophilic eubacterium Aquifex aeolicus.

The NADH:ubiquinone oxidoreductase (complex I) is the first enzyme of the respiratory chain and the entry point for most electrons. Generally, the bacterial complex I consists of 14 core subunits, homologues of which are also found in complex I of mitochondria. In complex I preparations from the hyperthermophilic bacterium Aquifex aeolicus we have identified 20 partially homologous subunits by combining MALDI-TOF and LILBID mass spectrometry methods. The subunits could be assigned to two different complex I isoforms, named NQOR1 and NQOR2. NQOR1 consists of subunits NuoA2, NuoB, NuoD2, NuoE, NuoF, NuoG, NuoI1, NuoH1, NuoJ1, NuoK1, NuoL1, NuoM1 and NuoN1, with an entire mass of 504.17 kDa. NQOR2 comprises subunits NuoA1, NuoB, NuoD1, NuoE, NuoF, NuoG, NuoH2, NuoI2, NuoJ1, NuoK1, NuoL2, NuoM2 and NuoN2, with a total mass of 523.99 kDa. Three Fe-S clusters could be identified by EPR spectroscopy in a preparation containing predominantly NQOR1. These were tentatively assigned to a binuclear center N1, and two tetranuclear centers, N2 and N4. The redox midpoint potentials of N1 and N2 are -273 mV and -184 mV, respectively. Specific activity assays indicated that NQOR1 from cells grown under low concentrations of oxygen was the more active form. Increasing the concentration of oxygen in the bacterial cultures induced formation of NQOR2 showing the lower specific activity.

Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis.

OBJECTIVE: Fatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS. METHODS: Patients with MS and self-reported fatigue were recruited via the website of the German MS Society and assigned via an automated randomisation generator (1:1, no blocking or stratification) to a 12-week online intervention (ELEVIDA, n=139, 82% female, mean age 40.8, median patient determined disease steps (PDDS) 3.0) or a waitlist control group (n=136, 79% female, mean age 41.9, median PDDS 3.0). The primary outcome was the Chalder Fatigue Scale. Outcomes were assessed at baseline, at week 12 (postintervention) and at follow-up (week 24). RESULTS: Compared with the control group, significantly greater reductions in Chalder Fatigue Scale scores were seen in the ELEVIDA group at week 12 (primary endpoint, intention-to-treat analysis: between-group mean difference 2.74 points; 95% CI 1.16 to 4.32; p=0.0007; effect size d=0.53), with effects sustained at week 24 (intention-to-treat analysis: between-group mean difference 2.19 points; 95% CI 0.57 to 3.82; p=0.0080). CONCLUSIONS: Our trial provides evidence for the effectiveness of a self-guided , internet-based intervention to reduce fatigue in MS. Interventions such as ELEVIDA may be a suitable low barrier, cost-effective treatment option for MS fatigue. TRIAL REGISTRATION NUMBER: ISRCTN registry (number ISRCTN25692173).

Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? An individual participant data meta-analysis.

BACKGROUND: Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. METHODS: Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. RESULTS: Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates. CONCLUSIONS: Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.

Impact and change of attitudes toward Internet interventions within a randomized controlled trial on individuals with depression symptoms.

BACKGROUND: Most individuals with depression do not receive adequate treatment. Internet interventions may help to bridge this gap. Research on attitudes toward Internet interventions might facilitate the dissemination of such interventions by identifying factors that help or hinder uptake and implementation, and by clarifying who is likely to benefit. This study examined whether attitudes toward Internet interventions moderate the effects of a depression-focused Internet intervention, and how attitudes change over the course of treatment among those who do or do not benefit. METHODS: We recruited 1,004 adults with mild-to-moderate depression symptoms and investigated how attitudes toward Internet interventions are associated with the efficacy of the program deprexis, and how attitudes in the intervention group change from pre to post over a 3 months intervention period, compared to a control group (care as usual). This study consists of a subgroup analysis of the randomized controlled EVIDENT trial. RESULTS: Positive initial attitudes toward Internet interventions were associated with greater efficacy (η2p  = .014) independent of usage time, whereas a negative attitude (perceived lack of personal contact) was associated with reduced efficacy (η2p  = .012). Users' attitudes changed during the trial, and both the magnitude and direction of attitude change were associated with the efficacy of the program over time (η2p  = .030). CONCLUSIONS: Internet interventions may be the most beneficial for individuals with positive attitudes toward them. Informing potential users about evidence-based Internet interventions might instill positive attitudes and thereby optimize the benefits such interventions can provide. Assessing attitudes prior to treatment might help identify suitable users.

Protocol for the ENCODE trial: evaluating a novel online depression intervention for persons with epilepsy.

BACKGROUND: Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet-administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. METHODS/DESIGN: This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). DISCUSSION: Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02791724 . Registered 01 June 2016.

Defining and Predicting Patterns of Early Response in a Web-Based Intervention for Depression.

BACKGROUND: Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment. OBJECTIVE: The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects. METHODS: We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression. RESULTS: Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (P<.001) and adherence (P=.03) in regard to the number of modules (number of modules with a duration of at least 10 minutes) and the number of assessments (P<.001), but not in regard to the overall amount of time using the system. Class membership significantly improved outcome prediction by 24.8% over patient intake characteristics (P<.001) and significantly added to the prediction of adherence (P=.04). CONCLUSIONS: These findings suggest that in Web-based interventions outcome and adherence can be predicted by patterns of early change, which can inform treatment decisions and potentially help optimize the allocation of scarce clinical resources.

Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial.

BACKGROUND: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. METHODS: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical settings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. RESULTS: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed signixFB01;cantly between groups (t825 = 6.12, p < 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). CONCLUSIONS: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications.

Vorvida: study protocol of a randomized controlled trial testing the effectiveness of Internet-based self-help program for the reduction of alcohol consumption for adults.

BACKGROUND: Problem drinking is an important global health concern, causing premature mortality and morbidity. Only few problem drinkers seek professional care, unfortunately, because of multiple barriers such as insufficient change motivation, fear of stigmatization or limited access to care. The aim of this study will be to examine the effectiveness of a novel Internet intervention termed Vorvida, which was developed based on established cognitive-behavioral therapy techniques with the aim of reducing problematic alcohol consumption. METHODS/DESIGN: A two-arm randomized control trial (RCT) will be conducted to determine whether using Vorvida results in greater reductions in self-reported problem drinking, compared with a care-as-usual/waitlist (CAU/WL) control group. There will be a baseline assessment (t0) and follow-up assessments after three (t1) and six months (t2). Inclusion criteria will be: minimum age of 18, an average consumption of alcohol >24/12 g (men/women) per day and an AUDIT-C score ≥ 3, as well as informed consent. Participants will be randomly assigned to the intervention or control condition at a ratio of 1:1. Recruitment, informed consent, randomization and assessment will be Internet-based. Primary outcome will be change in self-reported alcohol consumption between t0 and t1. Secondary outcomes will be self-reported drinking behavior, expectancies of effects of alcohol use, abstinence and relapse tendencies, self-efficacy and motivation to change. DISCUSSION: This study is expected to establish the extent to which a novel Internet intervention could contribute to reducing problem drinking among adults with mild to severe alcohol use disorders who may or may not seek or access a traditional treatments. Potentially, this program could be an effective and efficient tool to help reduce problem drinking on a population level because a great number of users can be reached simultaneously without adding burden to treating clinicians. TRIAL REGISTRATION: German Clinical Trial Registration (DRKS): DRKS00006104. Registered 14 April 2014.

Standardized processing of MALDI imaging raw data for enhancement of weak analyte signals in mouse models of gastric cancer and Alzheimer's disease.

Conventional mass spectrometry image preprocessing methods used for denoising, such as the Savitzky-Golay smoothing or discrete wavelet transformation, typically do not only remove noise but also weak signals. Recently, memory-efficient principal component analysis (PCA) in conjunction with random projections (RP) has been proposed for reversible compression and analysis of large mass spectrometry imaging datasets. It considers single-pixel spectra in their local context and consequently offers the prospect of using information from the spectra of adjacent pixels for denoising or signal enhancement. However, little systematic analysis of key RP-PCA parameters has been reported so far, and the utility and validity of this method for context-dependent enhancement of known medically or pharmacologically relevant weak analyte signals in linear-mode matrix-assisted laser desorption/ionization (MALDI) mass spectra has not been explored yet. Here, we investigate MALDI imaging datasets from mouse models of Alzheimer's disease and gastric cancer to systematically assess the importance of selecting the right number of random projections k and of principal components (PCs) L for reconstructing reproducibly denoised images after compression. We provide detailed quantitative data for comparison of RP-PCA-denoising with the Savitzky-Golay and wavelet-based denoising in these mouse models as a resource for the mass spectrometry imaging community. Most importantly, we demonstrate that RP-PCA preprocessing can enhance signals of low-intensity amyloid-ß peptide isoforms such as Aß1-26 even in sparsely distributed Alzheimer's ß-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo. We conclude that RP-PCA denoising may be a useful preprocessing step in biomarker discovery workflows.