Comparing a mindfulness- and CBT-based guided self-help Internet- and mobile-based intervention against a waiting list control condition as treatment for adults with frequent cannabis use: a randomized controlled trial of CANreduce 3.0.

BACKGROUND: Though Internet- and mobile-based interventions (IMIs) and mindfulness-based interventions (generally delivered in-situ) appear effective for people with substance use disorders, IMIs incorporating mindfulness are largely missing, including those targeting frequent cannabis use. METHODS: This paper details the protocol for a three-arm randomized controlled trial comparing a mindfulness-based self-help IMI (arm 1) and cognitive-behavioral therapy (CBT)-based self-help IMI (arm 2) versus being on a waiting list (arm 3) in their effectiveness reducing cannabis use in frequent cannabis users. Predictors of retention, adherence and treatment outcomes will be identified and similarities between the two active intervention arms explored. Both active interventions last six weeks and consist of eight modules designed to reduce cannabis use and common mental health symptoms. With a targeted sample size of n = 210 per treatment arm, data will be collected at baseline immediately before program use is initiated; at six weeks, immediately after program completion; and at three and six months post baseline assessment to assess the retention of any gains achieved during treatment. The primary outcome will be number of days of cannabis use over the preceding 30 days. Secondary outcomes will include further measures of cannabis use and use of other substances, changes in mental health symptoms and mindfulness, client satisfaction, intervention retention and adherence, and adverse effects. Data analysis will follow ITT principles and primarily employ (generalized) linear mixed models. DISCUSSION: This RCT will provide important insights into the effectiveness of an IMI integrating mindfulness to reduce cannabis use in frequent cannabis users. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Registry: ISRCTN14971662 ; date of registration: 09/09/2021.

Hands-off: Study protocol of a two-armed randomized controlled trial of a web-based self-help tool to reduce problematic pornography use.

BACKGROUND AND AIMS: The past-year prevalence of problematic pornography use (PPU) was 1-6% in adult populations. As a result of treatment obstacles and barriers, such as unaffordable treatments, only a minority of problematic pornography users may seek treatment. Having a free, online, self-help program may overcome treatment barriers and may help those individuals who cannot receive traditional or offline treatment for PPU. Although the effectiveness of such online programs reducing substance use and problematic gambling have been reported, no prior study has examined the efficacy of an online self-help intervention aiming to reduce PPU. METHODS: This two-armed randomized controlled trial (RCT) will examine the effectiveness of an online self-help program (Hands-off) to reduce PPU, while also considering psychopathological comorbidities. The six-week intervention condition includes six core modules developed to reduce PPU based on motivational interviewing, cognitive behavioral therapy, mindfulness, and wise social-psychological intervention techniques. The target sample size is 242 participants. Self-report questionnaires will be administered at baseline, right after the end of the intervention, at one-month, and three-month follow-ups after the end of the intervention. The primary outcome will be the level of PPU. Secondary outcomes will include pornography use frequency, pornography craving, pornography use-avoidance self-efficacy, sex mindset, sexual satisfaction, negative and positive emotions, and life satisfaction. Data will be analyzed on an intention-to-treat basis using linear mixed models. RESULTS: Results will be reported at conferences and published in a scientific peer-reviewed journal. The participants will be sent a lay-person-friendly summary of the results via e-mail.

A novel hybrid modeling approach for the evaluation of integrated care and economic outcome in heart failure treatment.

BACKGROUND: Demographic changes, increased life expectancy and the associated rise in chronic diseases pose challenges to public health care systems. Optimized treatment methods and integrated concepts of care are potential solutions to overcome increasing financial burdens and improve quality of care. In this context modeling is a powerful tool to evaluate potential benefits of different treatment procedures on health outcomes as well as health care budgets. This work presents a novel modeling approach for simulating different treatment procedures of heart failure patients based on extensive data sets from outpatient and inpatient care. METHODS: Our hybrid heart failure model is based on discrete event and agent based methodologies and facilitates the incorporation of different therapeutic procedures for outpatient and inpatient care on patient individual level. The state of health is modeled with the functional classification of the New York Heart Association (NYHA), strongly affecting discrete state transition probabilities alongside age and gender. Cooperation with Austrian health care and health insurance providers allowed the realization of a detailed model structure based on clinical data of more than 25,000 patients. RESULTS: Simulation results of conventional care and a telemonitoring program underline the unfavorable prognosis for heart failure and reveal the correlation of NYHA classes with health and economic outcomes. Average expenses for the treatment of NYHA class IV patients of €10,077 ± €165 were more than doubled compared to other classes. The selected use case of a telemonitoring program demonstrated potential cost savings within two years of application. NYHA classes II and III revealed most potential for additional treatment measures. CONCLUSION: The presented model allows performing extensive simulations of established treatment procedures for heart failure patients and evaluating new holistic methods of care and innovative study designs. This approach offers health care providers a unique, adaptable and comprehensive tool for decision making in the complex and socioeconomically challenging field of cardiovascular diseases.

Single-beat noninvasive imaging of ventricular endocardial and epicardial activation in patients undergoing CRT.

BACKGROUND: Little is known about the effect of cardiac resynchronization therapy (CRT) on endo- and epicardial ventricular activation. Noninvasive imaging of cardiac electrophysiology (NICE) is a novel imaging tool for visualization of both epi- and endocardial ventricular electrical activation. METHODOLOGY/PRINCIPAL FINDINGS: NICE was performed in ten patients with congestive heart failure (CHF) undergoing CRT and in ten patients without structural heart disease (control group). NICE is a fusion of data from high-resolution ECG mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed during native rhythm as well as during ventricular pacing using a bidomain theory-based heart model to solve the related inverse problem. During right ventricular (RV) pacing control patients showed a deterioration of the ventricular activation sequence similar to the intrinsic activation pattern of CHF patients. Left ventricular propagation velocities were significantly decreased in CHF patients as compared to the control group (1.6±0.4 versus 2.1±0.5 m/sec; p<0.05). CHF patients showed right-to-left septal activation with the latest activation epicardially in the lateral wall of the left ventricle. Biventricular pacing resulted in a resynchronization of the ventricular activation sequence and in a marked decrease of total LV activation duration as compared to intrinsic conduction and RV pacing (129±16 versus 157±28 and 173±25 ms; both p<0.05). CONCLUSIONS/SIGNIFICANCE: Endocardial and epicardial ventricular activation can be visualized noninvasively by NICE. Identification of individual ventricular activation properties may help identify responders to CRT and to further improve response to CRT by facilitating a patient-specific lead placement and device programming.

Genetic engineering of trimers of hypoallergenic fragments of the major birch pollen allergen, Bet v 1, for allergy vaccination.

An immunotherapy trial performed in allergic patients with hypoallergenic recombinant fragments, comprising aa 1-74 and 75-160 of the major birch pollen allergen, Bet v 1, has indicated that the induction of allergen-specific IgG responses may be an important mechanism of this treatment. To investigate whether the immunogenicity of the rBet v 1 fragments can be increased, recombinant trimers of the fragments were produced. For this purpose, DNA trimers of rBet v 1 aa 1-74 as well as of rBet v 1 aa 75-160 were subcloned into expression plasmid pET 17b, expressed in Escherichia coli and purified. The fragments as well as the fragment trimers showed a reduced IgE-binding capacity and allergenic activity compared to rBet v 1 wildtype when tested in allergic patients. Both rBet v 1 aa 75-160 monomer and trimer induced high titers of allergen-specific IgG1 Abs in mice. Interestingly, rBet v 1 aa 1-74 trimer induced a much higher IgG(1) response to rBet v 1 than rBet v 1 aa 1-74 monomer. Consequently, IgG Abs induced with the rBet v 1 aa 1-74 trimer inhibited birch pollen allergic patients' IgE-binding 10-fold more efficiently than IgG Abs induced with the monomer. Our data show that the immunogenicity of allergy vaccines can be increased by oligomerization.