Alcohol assessment and feedback by email for university students: main findings from a randomised controlled trial.

BACKGROUND: Brief interventions can be efficacious in changing alcohol consumption and increasingly take advantage of the internet to reach high-risk populations such as students. AIMS: To evaluate the effectiveness of a brief online intervention, controlling for the possible effects of the research process. METHOD: A three-arm parallel groups design was used to explore the magnitude of the feedback and assessment component effects. The three groups were: alcohol assessment and feedback (group 1); alcohol assessment only without feedback (group 2); and no contact, and thus neither assessment nor feedback (group 3). Outcomes were evaluated after 3 months via an invitation to participate in a brief cross-sectional lifestyle survey. The study was undertaken in two universities randomising the email addresses of all 14 910 students (the AMADEUS-1 study, trial registration: ISRCTN28328154). RESULTS: Overall, 52% (n = 7809) of students completed follow-up, with small differences in attrition between the three groups. For each of the two primary outcomes, there was one statistically significant difference between groups, with group 1 having 3.7% fewer risky drinkers at follow-up than group 3 (P = 0.006) and group 2 scoring 0.16 points lower than group 3 on the three alcohol consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) (P = 0.039). CONCLUSIONS: This study provides some evidence of population-level benefit attained through intervening with individual students

Alcohol assessment & feedback by e-mail for university student hazardous and harmful drinkers: study protocol for the AMADEUS-2 randomised controlled trial.

BACKGROUND: Alcohol is responsible for a large and growing proportion of the global burden of disease, as well as being the cause of social problems. Brief interventions are one component of comprehensive policy measures necessary to reduce these harms. Brief interventions increasingly take advantage of the Internet to reach large numbers of high risk groups such as students. The research literature on the efficacy and effectiveness of online interventions is developing rapidly. Although many studies show benefits in the form of reduced consumption, other intervention studies show no effects, for reasons that are unclear. Sweden became the first country in the world to implement a national system in which all university students are offered a brief online intervention via an e-mail. METHODS/DESIGN: This randomized controlled trial (RCT) aims to evaluate the effectiveness of this national system comprising a brief online intervention among university students who are hazardous and harmful drinkers. This study employs a conventional RCT design in which screening to determine eligibility precedes random allocation to immediate or delayed access to online intervention. The online intervention evaluated comprises three main components; assessment, normative feedback and advice on reducing drinking. Screening is confined to a single question in order to minimise assessment reactivity and to prevent contamination. Outcomes will be evaluated after 2 months, with total weekly alcohol consumption being the primary outcome measure. Invitations to participate are provided by e-mail to approximately 55,000 students in 9 Swedish universities. DISCUSSION: This RCT evaluates routine service provision in Swedish universities via a delay in offer of intervention to the control group. It evaluates effects in the key population for whom this intervention has been designed. Study findings will inform the further development of the national service provision. TRIAL REGISTRATION: ISRCTN02335307

The effect of question order on outcomes in the ORBITAL core outcome set for alcohol brief interventions among online help-seekers (QOBCOS): findings from a randomised factorial trial

OBJECTIVE: A core outcome set (COS) has been developed in alcohol brief intervention (ABI) research through international consensus. This study aimed to estimate order effects among questions in the COS. METHODS: Individuals aged 18 or older who searched online for alcohol-related help were invited to complete the COS. The order of questions was randomised following a factorial design. Primary outcomes were order effects among the COS items and patterns of attrition. RESULTS: Between 21/10/2020 and 26/11/2020, we randomised 7334 participants, of which 5256 responded to at least one question and were available for analyses. Current non-drinkers were excluded. We found evidence of higher self-reported average consumption and odds of harmful and hazardous drinking was found among those who first answered questions on recent consumption and impact of alcohol use. Lower self-reported recent consumption was found among those first asked about average consumption. Quality of life (QoL) was reported lower among those who first responded to when questions on impact of alcohol use were asked first, which in turn was lower among those who first answered question on when average consumption and QoL were asked first. Attrition was lowest when average consumption was asked first, and highest when QoL or impact of alcohol use was asked first. Median completion time for the COS was 4.3 min. CONCLUSIONS: Question order affects outcomes and attrition. If the aim is to minimize attrition, consumption measures should be asked before QoL and impact of alcohol use; however, this order impacts self-reported alcohol consumption and so researchers should be guided by study priorities. At a minimum, all participants should be asked the same questions in the same order. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN17954645)

Effectiveness of a digital intervention versus alcohol information for online help-seekers in Sweden : a randomised controlled trial

BACKGROUND: The ubiquity of Internet connectivity, and widespread unmet needs, requires investigations of digital interventions for people seeking help with their drinking. The objective of this study was to test the effectiveness of a digital alcohol intervention compared to existing online resources for help seekers. METHODS: This parallel randomised controlled trial included 2129 risky drinkers with access to a mobile phone and aged 18 years or older. Randomised sub-studies investigated consent procedures and control group design. Simple computerised randomisation was used. Participants were aware of allocation after randomisation; research personnel were not. The digital intervention was designed around weekly monitoring of alcohol consumption followed by feedback and tools for behaviour change. Primary outcomes were total weekly consumption (TWC) and frequency of heavy episodic drinking (HED), measured 2 and 4 months post-randomisation. RESULTS: Between 25/04/2019 and 26/11/2020, 2129 participants were randomised (intervention: 1063, control: 1066). Negative binomial regression was used to contrast groups, with both Bayesian and maximum likelihood inference. The posterior median incidence rate ratio (IRR) of TWC was 0.89 (95% CI = 0.81;0.99, 98.2% probability of effect, P-value = 0.033) at 2 months among 1557 participants and 0.77 (95% CI = 0.69;0.86, > 99.9% probability of effect, P-value 99.9% probability of effect, P-value = 0.0009) at 2 months among 1548 participants and 0.71 (95% CI = 0.63;0.79, probability of effect > 99.9%, P-value < 0.0001) at 4 months among 1424 participants. Analyses with imputed data were not markedly different. CONCLUSIONS: A digital alcohol intervention produced self-reported behaviour change among online help seekers in the general population. The internal and external validity of this trial is strong, subject to carefully considered study limitations arguably inherent to trials of this nature. Limitations include higher than anticipated attrition to follow-up and lack of blinding. TRIAL REGISTRATION: The trial was prospectively registered ( ISRCTN48317451 )

Mediators of effects of a digital alcohol intervention for online help-seekers : Findings from an effectiveness trial

BACKGROUND: Digital alcohol interventions have been shown to exert effects in helping individuals reduce their drinking. However, little is known about the mechanisms which mediate such effects. The objective of this study was to estimate natural direct and indirect effects of a digital alcohol intervention. METHODS: This secondary analysis of mediated effects used data from a randomised controlled trial which included individuals with unhealthy alcohol use with access to a mobile phone aged 18 years or older in Sweden. The comparator was basic alcohol and health information. The digital intervention was centrally designed around weekly monitoring of consumption followed by feedback and tools to support behaviour change. Mediated effects were estimated using measures from 1-, 2-, and 4-months post-randomisation. Primary outcomes were total weekly consumption (TWC) and frequency of heavy episodic drinking (HED). A counterfactual framework was used to estimate three hypothesised mediators: importance, knowledge of how to change (know-how), and confidence. RESULTS: Between 25/04/2019 and 26/11/2020, 2129 participants were randomised. The intervention improved know-how and confidence, which in turn mediated the effects on TWC and HED at 2- and 4-months. Analyses with imputed data were not markedly different. CONCLUSIONS: A digital alcohol intervention was found to exert effects in reducing consumption by means of improving individuals' knowledge of how to reduce their consumption and confidence in their ability to reduce. The use of face-valid single item measures is a study limitation notwithstanding observed findings, as is attrition and lack of blinding of participants

Effects of a waiting list control design on alcohol consumption among online help-seekers : protocol for a randomised controlled trial

INTRODUCTION: Sparse attention has been given to the design of control conditions in trials, despite their important role as contrasts for novel treatments, and thus as a key determinant of effect sizes. This undermines valid inferences on effect estimates in trials, which are fundamentally comparative in nature. Such challenges to understanding also makes generalisation of effect estimates complex, for example, it may not be clear to what degree real-world alternatives to the novel treatments in pragmatic trials are similar to the control conditions studied. The present study aims to estimate the effects of being allocated to a waiting list control condition. METHODS AND ANALYSIS: Individuals searching online for help to reduce their drinking will be invited to take part in a study. Individuals aged 18 years or older, who in the past month consumed six or more drinks on one occasion, or consumed 10 or more drinks the past week, will be eligible to participate. Both groups will receive identical feedback and advice on behaviour change; however, one group will be informed that they have to wait 1 month for the intervention materials. One month postrandomisation, participants will receive an email with the follow-up questionnaire measuring the primary outcomes: (1) frequency of heavy episodic drinking (defined as at study entry) in the past month; and (2) overall past week alcohol consumption. Differences between groups will be analysed using negative binomial regression models estimated using Bayesian inference. Recruitment will begin in October 2021. A Bayesian group sequential design will be employed to determine when to end enrolment (expected to be between 500 and 1500 individuals). ETHICS AND DISSEMINATION: The study was approved by the Swedish Ethical Review Authority on 2021-01-25 (Dnr 2020-06267). Findings will be disseminated in open access peer-reviewed journals no later than 2023. TRIAL REGISTRATION TRIAL: ISRCTN14959594; Pre-results

Reactions to being allocated to a waiting list control group in a digital alcohol intervention trial

OBJECTIVE: To study reactions of control group participants allocated to two different presentations of basic health information in a digital alcohol intervention trial. METHOD: Control participants were randomised to wait with one of two different presentations of basic health information. Multiple choice questions and free-text comments assessed reactions, four months post randomisation. Effects of differential health information on responses were estimated, as were associations between responses, baseline characteristics and change in alcohol consumption. RESULT: Of 1066 control group participants, 572 (54%) responded to the questionnaire. Contrasting two different presentations of basic health information revealed no statistically significant differences. Responses revealed that 38% were interested sufficiently to look at the information while 42% felt frustration, irritation, or disappointment about having to wait. Approximately 55% responded that they decided to reduce their drinking whilst 17% stated that they continued to drink as usual, and 11% gave up on the idea of reducing their drinking. The two latter groups reported markedly higher alcohol consumption at follow-up in comparison to the former (probability of association >99.9%). CONCLUSION: Being made to wait may invite negative research participation effects. PRACTICE IMPLICATION: Comparator guidance should be updated to reflect the potentially negative consequences which are under researched

Alcohol email assessment and feedback study dismantling effectiveness for university students (AMADEUS-1): study protocol for a randomized controlled trial

BACKGROUND: Alcohol causes huge problems for population health and for society, which require interventions with individuals as well as populations to prevent and reduce harms. Brief interventions can be effective and increasingly take advantage of the internet to reach high-risk groups such as students. The research literature on the effectiveness of online interventions is developing rapidly and is confronted by methodological challenges common to other areas of e-health including attrition and assessment reactivity and in the design of control conditions. METHODS/DESIGN: The study aim is to evaluate the effectiveness of a brief online intervention, employing a randomized controlled trial (RCT) design that takes account of baseline assessment reactivity, and other possible effects of the research process. Outcomes will be evaluated after 3 months both among student populations as a whole including for a randomized no contact control group and among those who are risky drinkers randomized to brief assessment and feedback (routine practice) or to brief assessment only. A three-arm parallel groups trial will also allow exploration of the magnitude of the feedback and assessment component effects. The trial will be undertaken simultaneously in 2 universities randomizing approximately 15,300 students who will all be blinded to trial participation. All participants will be offered routine practice intervention at the end of the study. DISCUSSION: This trial informs the development of routine service delivery in Swedish universities and more broadly contributes a new approach to the study of the effectiveness of online interventions in student populations, with relevance to behaviors other than alcohol consumption. The use of blinding and deception in this study raise ethical issues that warrant further attention. TRIAL REGISTRATION: ISRCTN28328154

Comprehensive annotation of the Parastagonospora nodorum reference genome using next-generation genomics, transcriptomics and proteogenomics

Parastagonospora nodorum, the causal agent of Septoria nodorum blotch (SNB), is an economically important pathogen of wheat (Triticum spp.), and a model for the study of necrotrophic pathology and genome evolution. The reference P. nodorum strain SN15 was the first Dothideomycete with a published genome sequence, and has been used as the basis for comparison within and between species. Here we present an updated reference genome assembly with corrections of SNP and indel errors in the underlying genome assembly from deep resequencing data as well as extensive manual annotation of gene models using transcriptomic and proteomic sources of evidence (https://github.com/robsyme/Parastagonospora_nodorum_SN15). The updated assembly and annotation includes 8,366 genes with modified protein sequence and 866 new genes. This study shows the benefits of using a wide variety of experimental methods allied to expert curation to generate a reliable set of gene models