Satisfaction with a digital support tool targeting alcohol consumption: perspectives from participants in a randomized control trial.

AIM: Intervention design may be improved through evaluating the feedback from those who have been exposed to such interventions. As such, here the perspectives of the intervention group from a recent randomized control trial investigating the effectiveness of a digital alcohol intervention, in terms of perceived suitability and usefulness of the support tool they engaged with, were investigated. METHODS: Respondents (N=475; 45% of the intervention group) answered five quantitative questions addressing user experience, completed the 10-item System Useability Scale, and were offered the opportunity to write free-text feedback. Quantitative measures were analysed using ordinal and linear regression with baseline characteristics as predictors, and free-text responses were evaluated using content analysis. RESULTS: Overall, respondents were positive towards the intervention in terms of it fitting their needs, the usefulness of the tools included, and the usefulness of text message content. The intervention was perceived as more helpful by respondents with lower total weekly alcohol consumption, higher self-reported confidence in their ability to reduce their drinking, and the perceived importance there of, at baseline. The free-text comments revealed the value of reminders as prompts to reflect on one's own drinking behaviour. Nonetheless, criticisms of the intervention were voiced, primarily highlighting the repetitive nature of the reminders and the lack of individuation in advice. Some also feltlike the intervention was impersonal and targeted only a specific drinking pattern. CONCLUSIONS: Experiences of the intervention group in this trial were generally positive, though there may be demand for more individualised, targeted intervention design.

Exploratory mixed methods analysis of self-authored content from participants in a digital alcohol intervention trial.

BACKGROUND: Digital interventions readily permit data capture of participant engagement with them. If future interventions are intended to be more interactive, tailored, or a useful resource offered to users, it may be valuable to examine such data. One module available in a digital alcohol intervention recently tested in a randomised control trial offered participants the opportunity to self-author prompts that were sent to them by a text message at a time of their choosing. This study thus aimed to evaluate these self-authored prompts to increase knowledge on how individuals negotiate behaviour change and assess whether intervention content can be improved in the future. METHODS: The self-authored prompts were evaluated qualitatively using a combination of content and thematic analysis. The identified themes and subcategories are exemplified using anonymized quotes, and the frequency that each identified theme was coded for among the prompts was calculated. Associations between baseline characteristics and the odds of authoring a prompt at all, as well as a prompt within each theme, were investigated using logistic regression. RESULTS: Five themes were identified (Encouragement Style, Level of Awareness, Reminders of reasons to reduce/quit, Strategies to reduce/quit, and Timescale), all with several subcategories. The prompts module was more likely to be used by women and older individuals, as well as those for whom reducing alcohol consumption was perceived as important, or who felt they had the know-how to do so. Participants who had immediate access to the support tool (intervention group) were more than twice as likely to author a prompt (OR = 2.36; probability of association > 99%) compared to those with 4-month delayed access (control group). CONCLUSIONS: Individuals who engaged with the prompts module showed evidence of using the information provided in the support tool in an active way, with several showing goal setting and making plans to change their drinking behaviour. Individuals also used this opportunity to remind themselves of personal and specific reasons they wanted to change their drinking, as well as to encourage themselves to do so.

Effects of a text messaging smoking cessation intervention amongst online help-seekers and primary health care visitors: findings from a randomised controlled trial.

BACKGROUND: Smoking continues to be a leading risk factor for several diseases globally. We hypothesised that an intervention delivered via text messages could help individuals who were looking to quit. METHODS: A two-arm, parallel-groups, randomised controlled trial was employed. Both groups received treatment as usual, with the intervention group also receiving a 12-week text messaging intervention. Participants were adult, weekly or more frequent smokers, recruited online and in primary health care centres. Research personnel were blinded, while participants were not. Primary outcomes were prolonged abstinence and point prevalence of abstinence, 3 and 6 months post-randomisation. All randomised participants were included in analyses. RESULTS: Between 18 September 2020 and 16 June 2022, we randomised 1012 participants (intervention: 505, control: 507). Outcome data was available for 67% (n = 682) of participants at 3 months and 64% (n = 643) at 6 months. At 3 months, the odds ratio (OR) of prolonged abstinence was 2.15 (95% compatibility interval [CoI] = 1.51; 3.06, probability of effect [POE] > 99.9%, p < 0.0001), and for point prevalence of abstinence, it was 1.70 (95% CoI = 1.18; 2.44, POE = 99.8%, p = 0.0034) in favour of the text messaging intervention. At 6 months, the OR of prolonged abstinence was 2.38 (95% CoI = 1.62; 3.57, POE > 99.9%, p = < 0.0001), and for point prevalence, it was 1.49 (95% CoI = 1.03; 2.14, POE = 98.3%, p = 0.0349) in favour of the text messaging intervention. Analyses with imputed data were not markedly different. CONCLUSIONS: Amongst general population help-seekers-who on average had smoked for 25 years-access to a 12-week text messaging intervention produced higher rates of self-reported smoking abstinence in comparison to treatment as usual only. The intervention could be part of the societal response to the burden which smoking causes; however, findings are limited by risk of bias due to attrition, self-reported outcomes, and lack of blinding. TRIAL REGISTRATION: The trial was preregistered in the ISRCTN registry on 27/07/2020 (ISRCTN13455271).

Digital multiple health behaviour change intervention targeting online help seekers: protocol for the COACH randomised factorial trial.

INTRODUCTION: Unhealthy lifestyle behaviours continue to be highly prevalent, including alcohol consumption, unhealthy diets, insufficient physical activity and smoking. There is a lack of effective interventions which have a large enough reach into the community to improve public health. Additionally, the common co-occurrence of multiple unhealthy behaviours demands investigation of efforts which address more than single behaviours. METHODS AND ANALYSIS: The effects of six components of a novel digital multiple health behaviour change intervention on alcohol consumption, diet, physical activity and smoking (coprimary outcomes) will be estimated in a factorial randomised trial. The components are designed to facilitate behaviour change, for example, through goal setting or increasing motivation, and are either present or absent depending on allocation (ie, six factors with two levels each). The study population will be those seeking help online, recruited through search engines, social media and lifestyle-related websites. Included will be those who are at least 18 years of age and have at least one unhealthy behaviour. An adaptive design will be used to periodically make decisions to continue or stop recruitment, with simulations suggesting a final sample size between 1500 and 2500 participants. Multilevel regression models will be used to analyse behavioural outcomes collected at 2 months and 4 months postrandomisation. ETHICS AND DISSEMINATION: Approved by the Swedish Ethical Review Authority on 2021-08-11 (Dnr 2021-02855). Since participation is likely motivated by gaining access to novel support, the main concern is demotivation and opportunity cost if the intervention is found to only exert small effects. Recruitment began on 19 October 2021, with an anticipated recruitment period of 12 months. TRIAL REGISTRATION NUMBER: ISRCTN16420548.

Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome.

We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.

Second generation γ-secretase modulators exhibit different modulation of Notch ß and Aß production.

The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-ß peptide (Aß) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aß formation and determines the pathogenic potential of Aß by generating the aggregation-prone Aß42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aß secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aß formation from producing the amyloid-prone Aß42 variant to shorter and less amyloidogenic Aß species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aß generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch ß and Aß production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aß and not Notch ß formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.