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Background: Recent trends in Switzerland indicate a concerning rise in simultaneous polysubstance use among adolescents, a practice marked by the concurrent or sequential consumption of multiple psychoactive substances, notably alcohol and cannabis, alongside prescription medications (e.g. benzodiazepines) and illicit drugs, resulting in dozens of fatal outcomes. However, data on simultaneous polysubstance use and evidence-based approaches to effective prevention is lacking., Aims of the Study: The study aimed to explore and gain insights into use patterns, use settings, use motives, harm-reduction strategies, concerns associated with substance use, and support and counselling services from the point of view of adolescents practicing simultaneous polysubstance use in Switzerland., Methods: An exploratory study was conducted via an online survey (n = 116) and two focus group discussions with affected Swiss adolescents aged 14 to 20. A mixed-methods approach was applied to gain insights and better understand the phenomenon of simultaneous polysubstance use among Swiss adolescents. Quantitative survey data obtained between November 2021 and March 2023 by means of convenience sampling - organised by distributing flyers (in three national languages) among several project partners, on the internet, over social media and by word of mouth - was analysed descriptively, whereas qualitative survey data and focus group data were thematically explored. A concurrent nested design was employed, utilising quantitative findings as a core foundation for addressing research questions, while qualitative findings were instrumental in validating and providing contextual depth to the results., Results: Our findings reveal a preference of the sample for combining alcohol with cannabis and/or other substances (e.g. benzodiazepines or hard drugs) in social settings, driven by diverse motives, including enhancement of experiences and partly maladaptive coping mechanisms leading to self-medication. Despite some awareness of the potential harms, there is a significant reliance on peer-shared strategies for harm reduction, highlighting a gap in formal support and counselling services, some of which are perceived by adolescents as lacking empathy and relevance., Conclusions: This study underscores the urgency of developing targeted, youth-centred interventions that resonate with the lived realities of adolescents, aiming not only to reduce substance use but also to address the broader psychosocial factors contributing to simultaneous polysubstance use. By shedding light on the complex dynamics of adolescent polysubstance use, our research contributes to the ongoing dialogue on effective prevention strategies, advocating for a holistic approach encompassing education, policy reform and community support to tackle this multifaceted public health challenge.

A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N -glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with ricin from different preparations and other cultivars and isoforms. A total of 15 different oligomannosidic or paucimannosidic structures were identified in CRM-LS-1. Paucimannose was mainly found within the A-chain and oligomannose constituted the major glycan type of the B-chain. Furthermore, the novel primary structure variants E138 and D138 and four different C-termini of the A-chain as well as two B-chain variants V250 and F250 were elucidated. While the glycan proportions and loci were similar among all variants in CRM-LS-1 and ricin isoforms D and E of all cultivars analysed, a different stoichiometry for isoforms D and E and the amino acid variants were found. This detailed physicochemical characterization of ricin regarding the glycan profile and amino acid sequence variations yields unprecedented insight into the molecular features of this protein toxin. The variable attributes discovered within different cultivars present signature motifs and may allow discrimination of the biotoxin's origin that are important in molecular forensic profiling. In conclusion, our data of in-depth CRM-LS-1 characterization combined with the analysis of other cultivars is representative for known ricin variants.

Background: The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms., Objective: We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran., Method: Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models., Discussion: This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT., Trial Registration: https://en.irct.ir/trial/53578 ., (© 2023. The Author(s).)

Background: Digital interventions are an emerging and promising avenue for addiction prevention and mental health promotion, but their reach and use are often limited, and little is known about the factors associated with youth accessibility. SmartCoach is a life skills training program for addiction prevention where adolescents are proactively invited for program participation in secondary school classes. The mobile phone-based program provides individualized coaching for a period of 4 months and addresses self-management skills, social skills, and substance use resistance skills. This study examined sociodemographic and other predictors of program participation and program use., Methods: A total of 476 adolescents in 28 secondary and upper secondary school classes in the German-speaking part of Switzerland were proactively invited for participation in the SmartCoach program. Using generalized linear mixed models (GLMMs), we examined predictors of both program participation and program use at the individual and school class levels., Results: In total, 315 (66.2%) of the present 476 adolescents gave their active consent and provided the necessary information to be included in the program. None of the individual sociodemographic characteristics significantly predicted program participation, however, the participation rate was significantly higher in upper secondary school classes (84%) than secondary school classes (59%). The mean number of interactions with the program was 15.9, i.e., participants took part in almost half of the 34 possible interactions with the SmartCoach program. None of the baseline characteristics on the level of the school class significantly predicted program use. On the level of the individual, the univariate models showed that, compared to the reference category of 14-year-old students, program use was significantly lower for students who were 16 or older. Furthermore, participants with a migration background or an origin from a non-German-speaking country showed significantly lower program use. Finally, students with a medium level of perceived stress showed higher program use compared to those with a low level of stress. Within the final multivariate model for program use, only the variable "origin from a non-German-speaking country" remained significant., Conclusions: SmartCoach is an attractive offer for young people, in which two out of three young people who are invited in the classroom to participate do so. Among the program participants, the use of the program is acceptable, with an average of almost half of the content being worked on. There is potential for improvement in terms of recruitment, especially in school classes with a lower level of education. The most important starting point for improving program use lies in taking greater account of needs and wishes of students with non-German-speaking countries of origin.

Background: At-risk alcohol use, particularly binge drinking, is widespread among adolescents and young adults in most Western countries. MobileCoach Alcohol is a mobile app-based program for alcohol prevention that provides individualized coaching using a conversational agent. The current study tested the acceptance, use, and evaluation of this newly developed program and explored its potential effectiveness., Methods: Longitudinal pre-post study among upper secondary and vocational school students in Switzerland. Within the MobileCoach Alcohol prevention program, a virtual coach motivated participants to deal with alcohol sensitively, and provided feedback on alcohol use and strategies to resist alcohol for a period of 10 weeks. Information was provided in weekly dialogs, within contests with other participants, and interactive challenges. By means of a follow-up survey after the end of the 10-week program, indicators of the use, acceptance, and effectiveness of the program were examined., Results: Between October 2020 and July 2022, the program was advertised in upper secondary and vocational schools. Recruiting schools and school classes was difficult due to the COVID-19 containment measures in place during this period. Nevertheless, the program could be implemented in 61 upper secondary and vocational school classes with a total of 954 participating students. Three out of four students who were present in the school classes participated in the MobileCoach Alcohol program and the associated study. Online follow up assessment at week 10 was completed by 272 program participants (28.4%). Based on program use and evaluations by the participants, the overall acceptance of the intervention was good. The proportion of students who engaged in binge drinking was significantly reduced from 32.7% at baseline to 24.3% at follow up. Furthermore, the longitudinal analyses revealed decreases in the maximum number of alcoholic drinks consumed on an occasion and the mean number of standard drinks per month, whereas self-efficacy to resist alcohol increased between baseline and follow up., Conclusions: The mobile app-based MobileCoach Alcohol program proved to be an attractive intervention, in which the majority of students were interested when proactively recruited at school classes. It allows for individualized coaching in large groups of adolescents and young adults and is promising for reducing at-risk alcohol use.

Background: Addictive behaviors such as tobacco/e-cigarette smoking, at-risk alcohol consumption, cannabis use or compulsive internet use are common among apprentices. ready4life is a mobile app-based preventive intervention program for apprentices that promotes life skills and reduces risky behavior. The present study tested the efficacy of ready4life for addiction prevention among apprentices in Switzerland within a controlled trial., Methods: Two-arm, cluster-randomized controlled trial including assessments at baseline and follow-up after 6 months. Participants of the intervention group received coaching by a conversational agent for 16 weeks. The main outcome measure was a composite score for addictive behaviors, which included (1) at-risk drinking, (2) tobacco/e-cigarette smoking, (3) cannabis use and (4) problematic internet use., Results: A total of 2275 students from 159 vocational school classes in Switzerland, were invited for study participation. Of these, 1351 (59.4%) students with a mean age of 17.3 years and a male proportion of 56.6% provided informed consent to participate. The follow up assessment at month 6 was completed by 962 (71.2%) study participants. The results concerning the primary outcome showed a stronger decrease of addictive behaviors between baseline and follow up in the intervention group compared to the control group. In particular, significant effects were observed for at-risk drinking and problematic Internet use, while no significant effects were observed for tobacco/e-cigarette smoking and cannabis use., Conclusions: The majority of apprentices invited for program participation within vocational schools participated in the ready4life program for addiction prevention. The mobile app-based coaching was effective in reducing risk behaviors such as at-risk drinking and problematic Internet use in a group of adolescents who have an especially high risk of engaging in addictive activities.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

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., (© 2022. The Author(s).)

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, M age  = 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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: Life skills are abilities for adaptive and positive behavior that enable individuals to deal effectively with the demands and challenges of everyday life. Life-skills training programs conducted within the school curriculum are effective in preventing the onset and escalation of substance use among adolescents. However, their dissemination is impeded due to their large resource requirements. Life-skills training provided via mobile phones may provide a more economic and scalable approach., Objective: The goal of this study was to test the appropriateness (ie, acceptance, use, and evaluation) and short-term efficacy of a mobile phone-based life-skills training program to prevent substance use among adolescents within a controlled trial., Methods: The study design was a two-arm, parallel-group, cluster-randomized controlled trial with assessments at baseline and follow-up assessments after 6 and 18 months. This report includes outcomes measured up to the 6-month follow-up. The efficacy of the intervention was tested in comparison to an assessment-only control group. The automated intervention program SmartCoach included online feedback and individually tailored text messages provided over 22 weeks. The contents were based on social cognitive theory and addressed self-management skills, social skills, and substance use resistance skills. Linear mixed models and generalized linear mixed models, as well as logistic or linear regressions, were used to investigate changes between baseline and 6-month follow-up in the following outcomes: 30-day prevalence rates of problem drinking, tobacco use, and cannabis use as well as quantity of alcohol use, quantity of cigarettes smoked, cannabis use days, perceived stress, well-being, and social skills., Results: A total of 1759 students from 89 Swiss secondary and upper secondary school classes were invited to participate in the study. Of these, 1473 (83.7%) students participated in the study; the mean age was 15.4 years (SD 1.0) and 55.2% (813/1473) were female. Follow-up assessments at 6 months were completed by 1233 (83.7%) study participants. On average, program participants responded to half (23.6 out of 50) of the prompted activities. Program evaluations underlined its appropriateness for the target group of secondary school students, with the majority rating the program as helpful and individually tailored. The results concerning the initial effectiveness of this program based on 6-month follow-up data are promising, with three of nine outcomes of the intention-to-treat analyses showing beneficial developments of statistical significance (ie, quantity of alcohol use, quantity of tobacco use, and perceived stress; P<.05) and another three outcomes (ie, problem drinking prevalence, cannabis use days, and social skills) showing beneficial developments of borderline significance (P<.10)., Conclusions: The results showed good acceptance of this intervention program that could be easily and economically implemented in school classes. Initial results on program efficacy indicate that it might be effective in both preventing or reducing substance use and fostering life skills; however, data from the final 18-month follow-up assessments will be more conclusive., Trial Registration: ISRCTN Registry ISRCTN41347061; https://doi.org/10.1186/ISRCTN41347061., (©Severin Haug, Raquel Paz Castro, Andreas Wenger, Michael Patrick Schaub. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 13.07.2021.)

Background and Aims: Buying-shopping disorder and its transferability to the online sector is controversial. This study investigates in-store and online shopping patterns by comparing data-based modeling to a diagnostic cut-off approach. Further aims were to test model equivalence for gender and identify socio-demographic risk factors., Methods: In a representative survey, the Bergen Shopping Addiction Scale (BSAS) was applied, using both an online and in-store version. Latent class analyses were followed by multinomial logistic regression analyses to investigate socio-demographic variables. Measurement invariance across genders was tested with multi-group comparisons., Results: With N = 1,012, 3-class solutions provided the best model fit for both in-store and online shopping. Most individuals (76, 86%) were grouped in non-addicted classes, followed by risky (21, 11%) and addicted classes (both 3%). Twenty-eight percent of individuals in the online addicted shopping class remained unidentified using the cut-off. For online shopping, only lower age and education differentiated classes significantly., Discussion: Results indicate a close link between online and in-store shopping, albeit with distinguishing features. The cut-off yielded findings discrepant from class probabilities. That buying-shopping disorder mainly affects younger women of lower educational level must be questioned, given the limited associations identified., Conclusions: It is important not only to consider different settings of pathological shopping, but also to focus on groups that may not have appeared at risk in previous investigations (e.g., men, older age). The BSAS cut-off warrants further research.

Background: E-mental health is an established mode of delivering treatment for common mental disorders in many high income countries. However, evidence of its effectiveness in lower income countries is lacking. This mixed methods study presents lessons learned and preliminary data on the feasibility of a minimally guided e-mental health intervention in Lebanon. The aim was to pilot test Step-by-Step, a WHO guided e-mental health intervention, and research methods prior to future, controlled testing., Methods: Participants were recruited using social media and advertisements in primary care clinics. Participants completed baseline and post-intervention questionnaires on depression symptoms (primary outcome, PHQ-8), anxiety symptoms, well-being, disability and self-perceived problem severity, and a client satisfaction questionnaire. In addition, seven completers, four drop-outs, 11 study staff, and four clinic managers were interviewed with responses thematically analyzed. Website analytics were used to understand participant behavior when using the website., Results: A total of 129 participants signed up via the Step-by-Step website. Seventy-four participants started session 1 after completing pre-test questionnaires and 26 completed both baseline and post-intervention data. Among those who completed post-assessments, depression symptoms improved (PHQ-8 scores (t=5.62, p < 0.001 two-tailed, df = 25). Wilcoxon signed ranks tests showed a significant difference between baseline and post-Step-by-Step scores on all secondary outcome measures. Client satisfaction data was positive. Interview responses suggested that the intervention could be made more appropriate for younger, single people, more motivating, and easier to use. Those who utilized the support element of the intervention were happy with their relationship with the non-specialist support person (e-helper), though some participants would have preferred specialist support. E-helpers would have liked more training on complex cases. Website analytics showed that many users dropped out before intervention start, and that some re-entered screening data having been excluded from the study., Conclusion: Step-by-Step skills and techniques, model of service integration, and its non-specialist support element are acceptable. Though the sample was small and non-controlled and drop-out was high, results suggest that it may be effective in reducing depression and anxiety symptoms and increasing well-being. Lessons learned will inform content revision, the development of an app version of Step-by-Step, and the research methodology of upcoming effectiveness studies., (Copyright © 2020 Harper Shehadeh, Abi Ramia, Cuijpers, El Chammay, Heim, Kheir, Saeed, van Ommeren, van’t Hof, Watts, Wenger, Zoghbi and Carswell.)

Background: In recent years, cocaine use has increased in many countries, but only a minority of users seek treatment. Cognitive behavioral therapy (CBT) is seen as first-choice face-to-face treatment. However, a web-based intervention might serve as an alternative., Aims: To test the efficacy of a web-based self-help intervention, with and without chat counseling, grounded in CBT, at reducing cocaine use in cocaine misusers not in treatment for a substance use disorder., Methods: Subjects were randomly assigned to (1) a self-help intervention with chat support, (2) a self-help intervention without chat support, or (3) a waiting list control group. The fully-automated self-help program consisted of eight modules based on motivational interviewing, self-control practices and CBT. The primary outcome was the quantity of cocaine use per week. Secondary outcomes included frequency of cocaine and other substance use and mental health symptoms. Linear regression analysis was performed to investigate changes in primary and secondary outcomes., Results: In total, 416 users registered online for the trial, of whom 311 completed the baseline assessment. Participants were predominantly male (73%) and averaged 33 years old (SD = 7.6). Despite considerable efforts on our part, only 47 of 311 (15.1%) subjects completed the 6-month follow-up assessment. Frequency of cocaine use and severity of cocaine dependence decreased only in the intervention groups. No significant difference in the primary outcome was observed between the study arms, but several differences in secondary outcomes were observed by complete case analyses., Conclusions: Many cocaine misusers from the general population and not otherwise in treatment could be reached and decreased their cocaine use utilizing a CBT-based online intervention. However, due to the high percentage of dropouts and serious difficulties reaching subjects for follow-up assessments, no conclusions can be drawn regarding study arm differences. Implications for future studies are discussed.

It is now widely accepted that nanometer sized bubbles, attached at a hydrophobic silica surface, can cause rupture of aqueous wetting films due to the so-called nucleation mechanism. But the knowledge of the existence of such nanobubbles does not give an answer to how the subprocesses of this rupture mechanism operate. The aim of this paper is to describe the steps of the rupture process in detail: (1) During drainage of the wetting film, the apex of the largest nanobubble comes to a distance from the wetting film surface, where surface forces are acting. (2) An aqueous "foam film" in nanoscale size is formed between the bubble and the wetting film surface; in this foam film different Derjaguin-Landau-Verwey-Overbeek (DLVO) forces are acting than in the surrounding wetting film. In the investigated system, hydrophobized silica/water/air, all DLVO forces in the wetting film are repulsive, whereas in the foam film the van der Waals force becomes attractive. (3) The surface forces over and around the apex of the nanobubble lead to a deformation of the film surfaces, which causes an additional capillary pressure in the foam film. An analysis of the pressure balance in the system shows that this additional capillary pressure can destabilize the foam film and leads to rupture of the foam film. (4) If the newly formed hole in the wetting film has a sufficient diameter, the whole wetting film is destabilized and the solid becomes dewetted. Experimental data of rupture thickness and lifetime of wetting films of pure electrolyte and surfactant solutions show that the stabilization of the foam film by surfactants has a crucial effect on the stability of the wetting film.