Therapist-guided internet treatment for alcohol use disorders

Background: Alcohol Use Disorders (AUD) are among the most common psychiatric disorders but the vast majority never receive treatment. Internet interventions have the potential to reach some of those who currently do not seek or receive treatment. Such interventions for alcohol problems of varying forms have been shown to be effective, generally rendering small effect sizes, and some studies suggest that adding therapist guidance to these interventions can augment their effects. Aims: The general aim of this thesis was to develop and evaluate therapist-guided internetbased treatment for AUD. Specifically, we aimed to investigate the added effect of therapist guidance to a previously evaluated internet treatment (study I), test feasibility and preliminary effects of a newly developed high-intensity internet treatment (study II), evaluate effects of high- as compared to low-intensity internet treatment and a wait-list control group (study III) and investigate predictors of adherence and low-risk drinking in the internet treatments in study III (study IV). Methods: In Study I, we conducted a randomized controlled trial (RCT) where all groups received access to the same internet treatment, with one group receiving therapist guidance via messages, one group receiving therapist guidance via messages or chat (choice) and one group not receiving any therapist guidance (n=80). In Study II, a newly developed highintensity therapist-guided internet treatment was tested in a pilot study among participants to investigate feasibility and preliminary effects (n=13). Study III was a second RCT where the high-intensity internet treatment from study II was tested against a low-intensity internet treatment and a wait list control group (n=166). In Study IV, we used data from study III to investigate predictors of 1) treatment adherence and 2) low-risk drinking at post-treatment and three-month follow-up. Results: The results from study I showed that the groups that received therapist guidance reduced their number of standard drinks to a significantly higher degree than the group receiving no guidance. Study II showed that the newly developed high-intensity treatment was feasible and acceptable, and was associated with a significant reduction in number of standard drinks among participants. Study III showed that the high-intensity group reduced the number of standard drinks and heavy drinking days significantly more than the wait-list control-group, and reduced their number of heavy drinking days significantly more than the low-intensity group at post-treatment but not at three-month follow-up. Study IV showed that participants’ rating of treatment credibility was predictive of treatment adherence, and that pre-treatment abstinence, male gender and two personality variables (a high degree of alexithymia and a low degree of antagonism) were predictive of low-risk drinking. Conclusion: The results in this thesis, provide support for the feasibility and efficacy of internet treatment for AUD, and offer interesting findings on predictors of outcome that should be investigated further. Overall, participants were satisfied with the treatments, and few negative effects were reported

What do we know about alcohol internet interventions aimed at employees?—A scoping review

BackgroundInternet interventions are a promising avenue for delivering alcohol prevention to employees. The objective of this scoping review was to map all research on alcohol internet interventions aimed at employees regardless of design, to gain an overview of current evidence and identify potential knowledge gaps.MethodsWe conducted a literature search in three data bases (PsycInfo, PubMed, and Web of Science). Eligibility criteria were that (1) the study targeted employees age ≥18 years; (2) the intervention was delivered predominantly online; (3) the study focused specifically or in part on alcohol use; and (4) the study was published in English in a peer-reviewed academic journal. Two reviewers independently screened, reviewed, and extracted data.ResultsTwenty studies were included, of which 10 were randomized controlled trials, five were secondary analyses, three were feasibility trials, one was a cohort study and one described the rationale and development of an intervention. No qualitative studies were found. Randomized trials tended to show effects when interventions were compared to waitlists but not when more intensive interventions were compared to less intensive ones. We identified two design-related aspects where studies differed; (1) whether all applicants were included regardless of alcohol use level and (2) whether the intervention was explicitly framed as alcohol-focused or not. Significant recruitment problems were noted in several studies.ConclusionsAlcohol internet interventions hold promise in delivering alcohol prevention to employees, but heterogeneity in study design and difficulties in recruitment complicate interpretation of findings.Systematic review registrationhttps://osf.io/25x7e/, Open Science Framework

Transcriptome sequencing reveals high isoform diversity in the ant Formica exsecta

Transcriptome resources for social insects have the potential to provide new insight into polyphenism, i.e., how divergent phenotypes arise from the same genome. Here we present a transcriptome based on paired-end RNA sequencing data for the ant Formica exsecta (Formicidae, Hymenoptera). The RNA sequencing libraries were constructed from samples of several life stages of both sexes and female castes of queens and workers, in order to maximize representation of expressed genes. We first compare the performance of common assembly and scaffolding software (Trinity, Velvet-Oases, and SOAPdenovo-trans), in producing de novo assemblies. Second, we annotate the resulting expressed contigs to the currently published genomes of ants, and other insects, including the honeybee, to filter genes that have annotation evidence of being true genes. Our pipeline resulted in a final assembly of altogether 39,262 mRNA transcripts, with an average coverage of >300X, belonging to 17,496 unique genes with annotation in the related ant species. From these genes, 536 genes were unique to one caste or sex only, highlighting the importance of comprehensive sampling. Our final assembly also showed expression of several splice variants in 6,975 genes, and we show that accounting for splice variants affects the outcome of downstream analyses such as gene ontologies. Our transcriptome provides an outstanding resource for future genetic studies on F. exsecta and other ant species, and the presented transcriptome assembly can be adapted to any non-model species that has genomic resources available from a related taxon.Peer reviewe

Optimizing internet-delivered cognitive behaviour therapy for alcohol misuse—a randomized factorial trial examining effects of a pre-treatment assessment interview and guidance

Background: Internet-delivered cognitive behavioral therapy (ICBT) for alcohol misuse has potential to radically improve access to evidence-based care, and there is a need to investigate ways to optimize its delivery in clinical settings. Guidance from a clinician has previously been shown to improve drinking outcomes in ICBT, and some studies suggest that pre-treatment assessments may contribute in initiating early change. The objective of this study was to investigate the added and combined effects of a pre-treatment assessment interview and guidance on the outcomes of ICBT for alcohol misuse delivered in an online therapy clinic. Methods: A 2X2 factorial randomized controlled trial was conducted where participants received access to an 8-week ICBT program, and either a pre-treatment assessment interview (Factor 1), guidance (Factor 2), a combination of these, or neither of these. Participants were 270 individuals (66.8% female, mean age = 46.5) scoring 8 or more on the Alcohol Use Disorders Identification Test and consuming 14 standard drinks or more in the preceding week. Primary outcomes were number of drinks consumed and number of heavy drinking days during the preceding week, 3 months post-treatment. Results: Large within-group effects were found in terms of alcohol reductions (dw ≥ 0.82, p < 0.001), but neither of the factors significantly improved drinking outcomes. Guidance was associated with greater adherence (i.e. completed modules). Conclusions: Neither a pre-treatment assessment interview nor guidance from a clinician appears to improve drinking outcomes resulting from internet-delivered cognitive behaviour therapy for alcohol misuse when delivered in a routine online therapy clinic. Trial registration: NCT03984786. Registered 13 June 2019, https://clinicaltrials.gov/ct2/show/NCT03984786. Keywords: Alcohol; Assessment reactivity; Cognitive behavior therapy; Guidance; Internet; Treatmen

What do we know about alcohol internet interventions aimed at employees?—A scoping review

Background: Internet interventions are a promising avenue for delivering alcohol prevention to employees. The objective of this scoping review was to map all research on alcohol internet interventions aimed at employees regardless of design, to gain an overview of current evidence and identify potential knowledge gaps. Methods: We conducted a literature search in three data bases (PsycInfo, PubMed, and Web of Science). Eligibility criteria were that (1) the study targeted employees age ≥18 years; (2) the intervention was delivered predominantly online; (3) the study focused specifically or in part on alcohol use; and (4) the study was published in English in a peer-reviewed academic journal. Two reviewers independently screened, reviewed, and extracted data. Results: Twenty studies were included, of which 10 were randomized controlled trials, five were secondary analyses, three were feasibility trials, one was a cohort study and one described the rationale and development of an intervention. No qualitative studies were found. Randomized trials tended to show effects when interventions were compared to waitlists but not when more intensive interventions were compared to less intensive ones. We identified two design-related aspects where studies differed; (1) whether all applicants were included regardless of alcohol use level and (2) whether the intervention was explicitly framed as alcohol-focused or not. Significant recruitment problems were noted in several studies. Conclusions: Alcohol internet interventions hold promise in delivering alcohol prevention to employees, but heterogeneity in study design and difficulties in recruitment complicate interpretation of findings. Systematic review registration: https://osf.io/25x7e/, Open Science Framework

Efficacy of a novel online integrated treatment for problem gambling and tobacco smoking: Results of a randomized controlled trial

Background and aimsProblem gambling and tobacco use are highly comorbid among adults. However, there are few treatment frameworks that target both gambling and tobacco use simultaneously (i.e., an integrated approach), while also being accessible and evidence-based. The aim of this two-arm open label RCT was to examine the efficacy of an integrated online treatment for problem gambling and tobacco use.MethodsA sample of 209 participants (M$_{age}$ = 37.66, SD = 13.81; 62.2% female) from North America were randomized into one of two treatment conditions (integrated [n = 91] or gambling only [n = 118]) that lasted for eight weeks and consisted of seven online modules. Participants completed assessments at baseline, after treatment completion, and at 24-week follow-up.ResultsWhile a priori planned generalized linear mixed models showed no condition differences on primary (gambling days, money spent, time spent) and secondary outcomes, both conditions did appear to significantly reduce problem gambling and smoking behaviours over time. Post hoc analyses showed that reductions in smoking and gambling craving were correlated with reductions in days spent gambling, as well as with gambling disorder symptoms. Relatively high (versus low) nicotine replacement therapy use was associated with greater reductions in gambling behaviours in the integrated treatment condition.Discussion and conclusionsWhile our open label RCT does not support a clear benefit of integrated treatment, findings suggest that changes in smoking and gambling were correlated over time, regardless of treatment condition, suggesting that more research on mechanisms of smoking outcomes in the context of gambling treatment may be relevant

Computer-Based Interventions for Problematic Alcohol Use:a Review of Systematic Reviews

PURPOSE: The aim of this review is to provide an overview of knowledge and knowledge gaps in the field of computer-based alcohol interventions by (1) collating evidence on the effectiveness of computer-based alcohol interventions in different populations and (2) exploring the impact of four specified moderators of effectiveness: therapeutic orientation, length of intervention, guidance and trial engagement.  METHODS: A review of systematic reviews of randomized trials reporting on effectiveness of computer-based alcohol interventions published between 2005 and 2015.  RESULTS: Fourteen reviews met the inclusion criteria. Across the included reviews, it was generally reported that computer-based alcohol interventions were effective in reducing alcohol consumption, with mostly small effect sizes. There were indications that longer, multisession interventions are more effective than shorter or single session interventions. Evidence on the association between therapeutic orientation of an intervention, guidance or trial engagement and reductions in alcohol consumption is limited, as the number of reviews addressing these themes is low. None of the included reviews addressed the association between therapeutic orientation, length of intervention or guidance and trial engagement.  CONCLUSIONS: This review of systematic reviews highlights the mostly positive evidence supporting computer-based alcohol interventions as well as reveals a number of knowledge gaps that could guide future research in this field

Key Intervention Characteristics in e-Health: Steps Towards Standardized Communication

PURPOSE: This paper reports expert opinion on e-health intervention characteristics that enable effective communication of characteristics across the diverse field of e-health interventions. The paper presents a visualization tool to support communication of the defining characteristics. METHODS: An initial list of e-health intervention characteristics was developed through an iterative process of item generation and discussion among the 12 authors. The list was distributed to 123 experts in the field, who were emailed an invitation to assess and rank the items. Participants were asked to evaluate these characteristics in three separate ways. RESULTS: A total of 50 responses were received for a response rate of 40.7%. Six respondents who reported having little or no expertise in e-health research were removed from the dataset. Our results suggest that 10 specific intervention characteristics were consistently supported as of central importance by the panel of 44 e-intervention experts. The weight and perceived relevance of individual items differed between experts; oftentimes, this difference is a result of the individual theoretical perspective and/or behavioral target of interest. CONCLUSIONS: The first iteration of the visualization of salient characteristics represents an ambitious effort to develop a tool that will support communication of the defining characteristics for e-health interventions aimed to assist e-health developers and researchers to communicate the key characteristics of their interventions in a standardized manner that facilitates dialog

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

The cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal cancer

Background: Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. Methods: The toxicity of aspirin and aspirin derivatives to OC and a colorectal cancer (CRC) cell line were investigated in the presence and absence of platins. Results: The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 CRC cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. Conclusion: These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins