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Abstract Background Compared to the general population, people who inject drugs have poor health and wellbeing. Longitudinal studies can provide insight into factors driving these worse health outcomes but are subject to methodological challenges, such as cohort attrition. The aim of this study was to assess and characterise attrition in a prospective cohort of people who inject drugs in Victoria, Australia. Methods Using annually collected self-reported data from The Melbourne Injecting Drug User Cohort Study (SuperMIX) from September 2008 to January 2021, we estimated the incidence of participants being lost-to-follow-up (LTFU), with an episode of being LTFU defined as participants not undertaking a follow-up interview within two years of their last interview. We utilised a multiple event discrete-time survival analysis on participant period-observation data to estimate the associations between key factors and LTFU. Key areas of exposure measurement in analyses were sociodemographic, drug use and mental health. Results A total of n = 1328 SuperMIX participants completed a baseline interview, with n = 489 (36.8%) LTFU, i.e. not completing a follow-up interview in the following two years. Increased attrition was observed among SuperMIX participants who were: born outside Australia, younger than 30 years, reporting having completed fewer years of education, not residing in stable accommodation, not in stable employment and not on opioid agonist therapy (OAT). Conclusions The attrition rate of the SuperMIX cohort has largely been stable throughout the duration of the study. Higher attrition rates among individuals at greater sociodemographic disadvantage and not on OAT suggest that additional efforts are required to retain these participants. Findings also suggest that SuperMIX might not be capturing data on adverse health and wellbeing outcomes among subpopulations at high risk of harm.

Abstract Background Inclusion in public health research of young people from low-income households and those from minority ethnic groups remains low. It is recognised that there is a need to change the way in which research is conducted so that it becomes more inclusive. The aim of this work was to identify novel and innovative ways to maximise recruitment and inclusion of diverse participants when doing co-production within very short time frames for emergency responses. Method We conducted interviews with young people from low-income and minority ethnic backgrounds, and members or leaders of groups or organisations supporting or representing young people from underserved communities. Results A total of 42 participants took part in an interview. This included 30 young people from low income or minority ethnic backgrounds and 12 community leaders/service providers. Of the 30 young people, 26 participants identified as female and 12 participants identified as being from a minority ethnic background. Participants discussed a number of interrelated barriers to research involvement and identified ways in which barriers may be reduced. Prejudice and discrimination experienced by young people from underserved communities has led to substantial mistrust of educational and governmental establishments. Rigid and unfamiliar research practices further limit the involvement of young people. Four themes were identified as ways of supporting involvement, including: making opportunities available for young people, adaptations to research governance, understanding and acknowledging challenges faced by young people, and ensuring reciprocal benefits. Conclusion This research explored barriers to engagement in rapid public health co-production. Working with communities to co-produce rapid recruitment and research procedures to suit the needs and the context in which young people live is necessary.

Abstract This is a process evaluation of a large UK-based randomised controlled trial (RCT) (n = 5602) evaluating the effectiveness of recommending an alcohol reduction app, Drink Less, compared with usual digital care in reducing alcohol consumption in increasing and higher risk drinkers. The aim was to understand whether participants’ engagement (‘self-reported adherence’) and behavioural characteristics were mechanisms of action underpinning the effectiveness of Drink Less. Self-reported adherence with both digital tools was over 70% (Drink Less: 78.0%, 95% CI = 77.6–78.4; usual digital care: 71.5%, 95% CI = 71.0–71.9). Self-reported adherence to the intervention (average causal mediation effect [ACME] = −0.250, 95% CI = −0.42, −0.11) and self-monitoring behaviour (ACME = −0.235, 95% CI = −0.44, −0.03) both partially mediated the effect of the intervention (versus comparator) on alcohol reduction. Following the recommendation (self-reported adherence) and the tracking (self-monitoring behaviour) feature of the Drink Less app appear to be important mechanisms of action for alcohol reduction among increasing and higher risk drinkers.

Abstract Background Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥ 65y) as compared to younger adults (

Objective To illustrate an evidence-, theory- and person-based approach to codesign the COMMUNICATE films that support parental decision-making about the human papillomavirus (HPV) vaccine for their teenagers.Design Codesign study.Setting Localities covered by two immunisation teams in London and the south-west of England.Methods The intervention planning phase involved combining evidence from a literature review with qualitative interview data to identify barriers and facilitators to HPV vaccine uptake, as well as design features that should be incorporated within the COMMUNICATE films. The intervention development phase involved identifying guiding principles for the COMMUNICATE films, mapping behaviour change techniques onto the behaviour change wheel and codesigning the COMMUNICATE films. Feedback from users informed modifications to maximise acceptability and feasibility and to support behaviour change.Results The primary and secondary evidence highlighted important content to include within the COMMUNICATE films: emphasise the benefits of the HPV vaccine, provide transparent information about the safety profile and side effects and emphasise the universality and commonality of HPV infection. A series of scripts were used to guide 4 film shoots to create the content in multiple community languages with 16 participants, including vaccine-hesitant, ethnically diverse parents and professionals. Overall, participants were positive about the films. Potential messengers and ways the films could be distributed, identified by parents, include local social media networks or text messages from general practices. The need for information about the HPV vaccine to be shared by schools ahead of consent being sought was also raised.Conclusions By using an integrated approach to intervention development, this study has begun to address the need for an intervention to support vaccine-hesitant, ethnically diverse parents’ decision-making about the HPV vaccination programme. A future study to codesign, implement and evaluate a communication strategy for the COMMUNICATE films is planned.

BackgroundThe extent to which interventions are perceived as acceptable to users impacts engagement and efficacy. ObjectiveIn this study, we evaluated the acceptability of (1) the smartphone app Drink Less (intervention) and (2) the National Health Service (NHS) alcohol advice web page (usual digital care and comparator) among adult drinkers in the United Kingdom participating in a randomized controlled trial evaluating the effectiveness of the Drink Less app. MethodsA subsample of 26 increasing- and higher-risk drinkers (Alcohol Use Disorders Identification Test score≥8) assigned to the intervention group (Drink Less; n=14, 54%; female: n=10, 71%; age: 22-72 years; White: n=9, 64%) or usual digital care group (NHS alcohol advice web page; n=12, 46%; female: n=5, 42%; age: 23-68 years: White: n=9, 75%) took part in semistructured interviews. The interview questions were mapped on to the 7 facets of acceptability according to the Theoretical Framework of Acceptability: affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy. Alongside these constructs, we also included a question on perceived personal relevance, which previous research has linked to acceptability and engagement. Framework and thematic analysis of data was undertaken. ResultsThe Drink Less app was perceived as being ethical, easy, user-friendly, and effective for the period the app was used. Participants reported particularly liking the tracking and feedback sections of the app, which they reported increased personal relevance and which resulted in positive affect when achieving their goals. They reported no opportunity cost. Factors such as negative affect when not meeting goals and boredom led to disengagement in the longer term for some participants. The NHS alcohol advice web page was rated as being easy and user-friendly with no opportunity costs. However, the information presented was not perceived as being personally relevant or effective in changing drinking behavior. Most participants reported neutral or negative affect, most participants thought the alcohol advice web page was accessible, and some participants reported ethical concerns around the availability of suggested resources. Some participants reported that it had acted as a starting point or a signpost to other resources. Participants in both groups discussed motivation to change and contextual factors such as COVID-19 lockdowns, which influenced their perceived self-efficacy regardless of their assigned intervention. ConclusionsDrink Less appears to be an acceptable digital intervention among the recruited sample. The NHS alcohol advice web page was generally considered unacceptable as a stand-alone intervention among the recruited sample, although it may signpost and help people access other resources and interventions.

Abstract Background It is not yet fully understood to what extent in-flight transmission contributed to the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This study aimed to determine the occurrence and extent of SARS-CoV-2 transmission in-flight and assess factors associated with transmission risk to inform future control strategies. Methods Retrospective cohort study using data obtained from contact tracing of international flights arriving in England between 02/08/2021–15/10/2021. Transmission risk was estimated by calculating the secondary attack rate (SAR). Univariable and multivariable analyses of the SAR by specific risk factors was undertaken, including: number of in-flight index cases; number of symptomatic index cases; contact vaccination status; flight duration; proximity to the index case(s); contact age. Results 11,307 index cases linked to 667,849 contacts with 5,289 secondary cases reported. In-flight SAR was 0.79% (95% CI: 0.77–0.81). Increasing numbers of symptomatic cases (when > 4 index cases compared to one index case aOR 1.85; 95% CI: 1.40–2.44) and seating proximity to an index case (seated within compared to outside of two rows OR 1.82; 95% CI: 1.50–2.22) were associated with increased risk of secondary cases. Full vaccination history was protective (aOR 0.52; 95% CI: 0.47–0.57). Conclusions This study confirms that in-flight transmission of SARS-CoV-2 occurred. There are factors associated with increased risk of infection. Contact tracing identified exposed persons who subsequently developed infection. A targeted approach to contact tracing passengers with the highest exposure risk could be an effective use of limited public health resources.

Abstract Background The English schools-based human papillomavirus (HPV) vaccination programme has the potential to eliminate HPV-related cancers if high uptake is achieved. However, unmet information needs among some parents may contribute to persisting lower uptake among minority ethnic groups. Through this study we aimed to understand the information needs of vaccine-hesitant, ethnically diverse parents during decision-making about the HPV vaccine for their adolescent child, to inform the future development of tailored communication materials. Methods Recruitment was facilitated thorough healthcare and community organisations within London and the South West of England. Semi-structured interviews took place between April and August 2023. Thematic analysis was undertaken, assisted by NVivo software. Results Of the 29 parents interviewed, the majority were mothers (79%), belonged to a minority ethnic group (88%), and had an adolescent child unvaccinated against HPV (72%). Five of the interviews were undertaken in the participants’ primary language with translation support. Most parents interviewed had limited knowledge about the HPV vaccine and appeared conflicted as to whether vaccines could offer benefits to health. Misunderstanding around the potential of developing serious side-effects (e.g. fertility issues, developing cancer) were factors that could negatively impact decision-making by parents. Stigma associated with the sexual transmissibility of HPV did not always negatively impact decision-making. However, some parents chose not to vaccinate on the basis of perceptions of low risk and a preference to provide education about sexual behaviours to their adolescent child. Conclusions Tailoring communication materials to address misunderstandings could support informed decision-making by vaccine hesitant parents for their adolescent children to be vaccinated against HPV. Future communication materials about the HPV vaccine should highlight the benefits of protection against cancer to increase parents’ motivation for protect their adolescent child; provide accurate convincing information in relation to the excellent safety profile; and emphasise the importance of providing HPV vaccine at the recommended age, all alongside communicating the universality and commonality of HPV infection. Trial registration N/A.

Abstract Background The 2022-23 mpox epidemic is the first-time sustained community transmission had been reported in countries without epidemiological links to endemic areas. During that period, the outbreak almost exclusively affected sexual networks of gay, bisexual, or other men who have sex with men (GBMSM) and people living with HIV. In efforts to control transmission, multiple public health measures were implemented, including vaccination, contact tracing and isolation. This study examines knowledge, attitudes, and perceptions of mpox among a sample of GBMSM during the 2022-23 outbreak in the UK, including facilitators for and barriers to the uptake of public health measures. Methods Interviews were conducted with 44 GBMSM between May and December 2022. Data were analysed using reflexive thematic analysis. Positive and negative comments pertaining to public health measures were collated in a modified version of a ‘table of changes’ to inform optimisations to public health messages and guidance. Results Most interviewees were well informed about mpox transmission mechanisms and were either willing to or currently adhering to public health measures, despite low perceptions of mpox severity. Measures that aligned with existing sexual health practices and norms were considered most acceptable. Connections to GBMSM networks and social media channels were found to increase exposure to sexual health information and norms influencing protective behaviours. Those excluded or marginalized from these networks found some measures challenging to perform or adhere to. Although social media was a key mode of information sharing, there were preferences for timely information from official sources to dispel exaggerated or misleading information. Conclusions There are differential needs, preferences, and experiences of GBMSM that limit the acceptability of some mitigation and prevention measures. Future public health interventions and campaigns should be co-designed in consultation with key groups and communities to ensure greater acceptability and credibility in different contexts and communities.

Abstract Background During the early “containment” phase of the COVID-19 response in England (January-March 2020), contact tracing was managed by Public Health England (PHE). Adherence to self-isolation during this phase and how people were making those decisions has not previously been determined. The aim of this study was to gain a better understanding of decisions around adherence to self-isolation during the first phase of the COVID-19 response in England. Methods A mixed-methods cross sectional study was conducted, including an online survey and qualitative interviews. The overall pattern of adherence was described as never leaving home, leaving home for lower-contact reasons and leaving home for higher-contact reasons. Fisher’s exact test was used to test associations between adherence and potentially predictive binary factors. Factors showing evidence of association overall were then considered in relation to the three aspects of adherence individually. Qualitative data were analysed using inductive thematic analysis. Results Of 250 respondents who were advised to self-isolate, 63% reported not leaving home at all during their isolation period, 20% reported leaving only for lower-contact activities (dog walking or exercise) and 16% reported leaving for higher-contact, and therefore higher-risk, reasons. Factors associated with adherence to never going out included: the belief that following isolation advice would save lives, experiencing COVID-19 symptoms, being advised to stay in their room, having help from outside and having regular contact by text message from PHE. Factors associated with non-adherence included being angry about the advice to isolate, being unable to get groceries delivered and concerns about losing touch with friends and family. Interviews highlighted that a sense of duty motivated people to adhere to isolation guidance and where people did leave their homes, these decisions were based on rational calculations of the risk of transmission – people would only leave their homes when they thought they were unlikely to come into contact with others. Conclusions Understanding adherence to isolation and associated reasoning during the early stages of the pandemic is essential to pandemic preparedness for future emerging infectious disease outbreaks. Individuals make complex decisions around adherence by calibrating transmission risks, therefore treating adherence as binary should be avoided.

Abstract Background Skin and soft tissue infections (SSTI) among people who inject drugs (PWID) are a public health concern. This study aimed to co-produce and assess the acceptability and feasibility of a behavioural intervention to prevent SSTI. Methods The Person-Based Approach (PBA) was followed which involves: (i) collating and analysing evidence; (ii) developing guiding principles; (iii) a behavioural analysis; (iv) logic model development; and (v) designing and refining intervention materials. Co-production activities with target group representatives and key collaborators obtained feedback on the intervention which was used to refine its design and content. The intervention, harm reduction advice cards to support conversation between service provider and PWID and resources to support safer injecting practice, was piloted with 13 PWID by four service providers in Bristol and evaluated using a mixed-methods approach. Semi-structured interviews were conducted with 11 PWID and four service providers. Questionnaires completed by all PWID recorded demographic characteristics, SSTI, drug use and treatment history. Interviews were analysed thematically and questionnaires were analysed descriptively. Results Published literature highlighted structural barriers to safer injecting practices, such as access to hygienic injecting environments and injecting practices associated with SSTI included: limited handwashing/injection-site swabbing and use of too much acidifier to dissolve drugs. Co-production activities and the literature indicated vein care and minimisation of pain as PWID priorities. The importance of service provider–client relationships and non-stigmatising delivery was highlighted through the co-production work. Providing practical resources was identified as important to address environmental constraints to safer injecting practices. Most participants receiving the intervention were White British, male, had a history of SSTI and on average were 43.6 years old and had injected for 22.7 years. The intervention was well-received by PWID and service providers. Intervention content and materials given out to support harm reduction were viewed positively. The intervention appeared to support reflections on and intentions to change injecting behaviours, though barriers to safer injecting practice remained prominent. Conclusions The PBA ensured the intervention aligned to the priorities of PWID. It was viewed as acceptable and mostly feasible to PWID and service providers and has transferability promise. Further implementation alongside broader harm reduction interventions is needed.

Abstract Background Hepatitis B virus (HBV) epidemiology in Europe differs by region and population risk group, and data are often incomplete. We estimated chronic HBV prevalence as measured by surface antigen (HBsAg) among general and key population groups for each country in the European Union, European Economic Area and the United Kingdom (EU/EEA/UK), including where data are currently unavailable. Methods We combined data from a 2018 systematic review (updated in 2021), data gathered directly by the European Centre for Disease Control (ECDC) from EU/EEA countries and the UK and further country-level data. We included data on adults from the general population, pregnant women, first time blood donors (FTBD), men who have sex with men (MSM), prisoners, people who inject drugs (PWID), and migrants from 2001 to 2021, with three exceptions made for pre-2001 estimates. Finite Mixture Models (FMM) and Beta regression were used to predict country and population group HBsAg prevalence. A separate multiplier method was used to estimate HBsAg prevalence among the migrant populations within each country, due to biases in the data available. Results There were 595 included studies from 31 countries (N = 41,955,969 people): 66 were among the general population (mean prevalence ( $$\stackrel{-}{p}$$ ) 1.3% [range: 0.0-7.6%]), 52 among pregnant women ( $$\stackrel{-}{p}=$$ 1.1% [0.1–5.3%]), 315 among FTBD ( $$\stackrel{-}{p}=$$ 0.3% [0.0-6.2%]), 20 among MSM ( $$\stackrel{-}{p}=$$ 1.7% [0.0-11.2%]), 34 among PWID ( $$\stackrel{-}{p}=$$ 3.9% [0.0-16.9%]), 24 among prisoners ( $$\stackrel{-}{p}=$$ 2.9% [0.0-10.7%]), and 84 among migrants ( $$\stackrel{-}{p}=$$ 7.0% [0.2–37.3%]). The FMM grouped countries into 3 classes. We estimated HBsAg prevalence among the general population to be 1% for most countries. Portugal had the highest estimated prevalence of HBsAg among migrants (5.0%), with the other highest prevalences mostly seen in Southern Europe. Conclusions We estimated HBV prevalence for each population group within each EU/EAA country and the UK, with general population HBV prevalence to be

BackgroundRandomized controlled trials (RCTs) with no in-person contact (ie, remote) between researchers and participants offer savings in terms of cost and time but present unique challenges. ObjectiveThe goal of this study is to examine the differences between different forms of remote recruitment (eg, National Health Service [NHS] website, social media, and radio advertising) in the proportion of participants recruited, demographic diversity, follow-up rates, and cost. We also examine the cost per participant of sequential methods of follow-up (emails, phone calls, postal surveys, and postcards). Finally, our experience with broader issues around study advertising and participant deception is discussed. MethodsWe conducted a descriptive analysis of 5602 increasing-and-higher-risk drinkers (Alcohol Use Disorders Identification Test score ≥8), taking part in a 2-arm, parallel group, remote RCT with a 1:1 allocation, comparing the intervention (Drink Less app) with usual digital care (NHS alcohol advice web page). Participants were recruited between July 2020 and March 2022 and compensated with gift vouchers of up to £36 (a currency exchange rate of £1=US $1.26988 is applicable) for completing follow-up surveys, with 4 stages of follow-up: email reminders, phone calls, postal survey, and postcard. ResultsThe three main recruitment methods were advertisements on (1) social media (2483/5602, 44.32%), (2) the NHS website (1961/5602, 35.01%), and (3) radio and newspapers (745/5602, 13.3%), with the remaining methods of recruitment accounting 7.37% (413/5602) of the sample. The overall recruitment cost per participant varied from £0 to £11.01. Costs were greater when recruiting participants who were men (£0-£28.85), from an ethnic minority group (£0-£303.81), and more disadvantaged (£0-£49.12). Targeted approaches were useful for recruiting more men but less useful in achieving diversity in ethnicity and socioeconomic status. Follow-up at 6 months was 79.58% (4458/5602). Of those who responded, 92.4% (4119/4458) responded by email. Each additional stage of follow-up resulted in an additional 2-3 percentage points of the overall sample being followed up, although phone calls, postal surveys, and postcards were more resource intensive than email reminders. ConclusionsFor remote RCTs, researchers could benefit from using a range of recruitment methods and cost-targeted approaches to achieve demographic diversity. Automated emails with substantial financial incentives for prompt completion can achieve good follow-up rates, and sequential, offline follow-up options, such as phone calls and postal surveys, can further increase follow-up rates but are comparatively expensive. We also make broader recommendations focused on striking the right balance when designing remote RCTs. Careful planning, ongoing maintenance, and dynamic decision-making are required throughout a trial to balance the competing demands of participation among those eligible, deceptive participation among those who are not eligible, and ensuring no postrandomization bias is introduced by data-checking protocols.

Background: The English schools-based human papillomavirus (HPV) vaccination programme is routinely offered to all young people aged 12–13 years. The EDUCATE lesson was developed to overcome barriers to uptake related to unmet information needs by providing young people with information and answering questions they may have about the HPV vaccine. The resource comprises a PowerPoint presentation, interspersed with five short films and a guidance document for professionals delivering the lesson. Adopting public health research into practice is challenging and few papers describe the process. This paper reports the initial use of the EDUCATE resource in schools and the process involved in supporting wider implementation. Study design: Implementation and knowledge mobilisation. Methods: Five secondary schools supported implementation of the EDUCATE resource. Delivery took place during April and December 2022 and was observed in four schools, with feedback obtained from two school staff members and 15 young people. Alongside this, meetings were held with over 80 stakeholders with the aim of identifying possible policy levers to encourage use of the EDUCATE resource, and to enhance understanding of how wider scale and sustained impact can be achieved. Results: Overall, the resource was positively received by school staff and young people engaged well during the lesson. As a result of the stakeholder networking activities, the research team worked with the Personal, Social, Health and Economic (PSHE) Association to adapt the materials to meet their Quality Assessment and incorporate elements, such as more interactive activities, requested during the implementation study. Conclusion: The EDUCATE resource has the potential to change practice by enhancing information provision about the HPV vaccine in schools and supporting young people nationally to make informed decisions. Key learnings from the project include the importance of integrating input from target users at all stages of the research process, pragmatism in relation to evaluation research designs, and incentivising researchers to undertake translation activities through further funding and a greater focus on impact. Together, these can help facilitate the availability of public health resources and their adoption into ‘real-world’ practice.

Objective In September 2020, 15 861 SARS-CoV-2 case records failed to upload from the Second Generation Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, delaying the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on population health outcomes: transmission events, hospitalisations and mortality. Previously, a modelling study suggested a substantial impact.Design Observational study.Setting England.Population Individuals testing positive for SARS-CoV-2 and their reported contacts.Main outcome measures Secondary attack rates (SARs), hospitalisations and deaths among primary and secondary contacts were calculated, compared with all other concurrent, unaffected cases. Affected SGSS records were matched to CTAS records. Successive contacts and cases were identified and matched to hospital episode and mortality outcomes.Results Initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared with the control group (3 days). This was associated with lower completion of contact tracing: 80% (95% CI: 79% to 81%) in delay group and 83% (95% CI: 83% to 84%) in control group. There was some evidence to suggest increased transmission to non-household contacts among those affected by the delay. The SAR for non-household contacts was higher among secondary contacts in the delay group than the control group (delay group: 7.9%, 95% CI: 6.5% to 9.2%; control group: 5.9%, 95% CI: 5.3% to 6.6%). There did not appear to be a significant difference between the delay and control groups in the odds of hospitalisation (crude OR: 1.1 (95% CI: 0.9 to 1.2)) or death (crude OR: 0.7 (95% CI: 0.1 to 4.0)) among secondary contacts.Conclusions Our analysis suggests that the delay in contact tracing had a limited impact on population health outcomes; however, contact tracing was not completed for all individuals, so some transmission events might not be captured.

Abstract Background Hepatitis C Virus (HCV) is a public health threat which contributes substantially to the global burden of liver disease. There is much debate about effective approaches to scaling up diagnosis of HCV among risk groups. Tayside, a region in the East of Scotland, developed low-threshold community pathways for HCV to lay the foundations of an elimination strategy. In this retrospective study, we sought to: quantify the contribution of community pathways to increasing HCV diagnosis; understand if shifting diagnosis to community settings led to a higher proportion of individuals tested for HCV being actively infected; and describe functional characteristics of the care pathways. Methods Descriptive statistics were used to for analysis of routinely-collected HCV testing data from 1999 to 2017, and a review of the development of the care pathways was undertaken. Community-based testing was offered through general practices (GP); nurse outreach clinics; prisons; drug treatment services; needle and syringe provision (NSP) sites; community pharmacies; and mosques. Results Anti-HCV screening was undertaken on 109,430 samples, of which 5176 (4.7%) were reactive. Of all samples, 77,885 (71.2%) were taken in secondary care; 25,044 (22.9%) in GPs; 2970 (2.7%) in prisons; 2415 (2.2%) in drug services; 753 (0.7%) in NSPs; 193 (0.2%) pharmacies; and 170 (0.1%) in mosques. The highest prevalence of HCV infection among those tested was in NSP sites (26%), prisons (14%), and drug treatment centres (12%). Conclusions Decentralised care pathways, particularly in harm reduction and other drug service settings, were key to increasing diagnosis of HCV in the region, but primary and secondary care remain central to elimination efforts.

Abstract Background The national shielding programme was introduced by UK Government at the beginning of the COVID-19 pandemic, with individuals identified as clinically extremely vulnerable (CEV) offered advice and support to stay at home and avoid all non-essential contact. This study aimed to explore the impact and responses of “shielding” on the health and wellbeing of CEV individuals in Southwest England during the first COVID-19 lockdown. Methods A two-stage mixed methods study, including a structured survey (7 August—23 October 2020) and semi-structured telephone interviews (26 August—30 September 2020) with a sample of individuals who had been identified as CEV and advised to “shield” by Bristol, North Somerset & South Gloucestershire (BNSSG) Clinical Commissioning Group (CCG). Results The survey was completed by 203 people (57% female, 54% > 69 years, 94% White British, 64% retired) in Southwest England identified as CEV by BNSSG CCG. Thirteen survey respondents participated in follow-up interviews (53% female, 40% > 69 years, 100% White British, 61% retired). Receipt of ‘official’ communication from NHS England or General Practitioner (GP) was considered by participants as the legitimate start of shielding. 80% of survey responders felt they received all relevant advice needed to shield, yet interviewees criticised the timing of advice and often sought supplementary information. Shielding behaviours were nuanced, adapted to suit personal circumstances, and waned over time. Few interviewees received community support, although food boxes and informal social support were obtained by some. Worrying about COVID-19 was common for survey responders (90%). Since shielding had begun, physical and mental health reportedly worsened for 35% and 42% of survey responders respectively. 21% of survey responders scored ≥ 10 on the PHQ-9 questionnaire indicating possible depression and 15% scored ≥ 10 on the GAD-7 questionnaire indicating possible anxiety. Conclusions This research highlights the difficulties in providing generic messaging that is applicable and appropriate given the diversity of individuals identified as CEV and the importance of sharing tailored and timely advice to inform shielding decisions. Providing messages that reinforce self-determined action and assistance from support services could reduce the negative impact of shielding on mental health and feelings of social isolation.

In recent years, a range of academic disciplines have emphasized the potential benefits of prioritizing meaningful engagement with individuals and communities who have lived and have living experience with the topics, phenomena and problems researchers seek to study. In March 2022, we were asked to produce a paper to inform a university workshop and training materials to help students and faculty engage with participatory methods. In turn, we conducted a rapid scoping review of reviews to document key recommendations relating to methodology, logistics and ethics within the various modes of participatory research. Searches were conducted in Web of Science, SCOPUS, ProQuest, Pub Med, OVID (including Medline, PschyInfo/EMBASE, APAPsych) to identify published academic reviews (e.g., systematic, scoping, literature reviews and evidence gap maps), for best practices relating to participatory research. This approach drew out aggregated best practices and lessons learned across many primary studies and increased the speed of the review. From 276 studies imported for screening, 43 full-text studies were assessed for eligibility and 28 were deemed relevant for full inclusion. Results are presented as: 1) participatory research recommendations for researchers; and 2) participatory research recommendations for academic institutions. Three sub-themes emerged within the context of suggestions for researchers engaging with participatory methods: 1) early-stage considerations for study design and planning; 2) conducting the research; and 3) dissemination and knowledge exchange. This rapid scoping review highlights key recommendations for researchers interested in using participatory approaches in their own research, and for academic and institutional stakeholders who aim to support these practices.

Background: The SARS-CoV-2 pandemic has highlighted the risk of infection in long-term care facilities (LTCF) and the vulnerability of residents to severe outcomes. Environmental surveillance may help detect pathogens early and inform Infection Prevention and Control (IPC) measures in these settings. Methods: Upon notification of SARS-CoV-2 outbreaks, LTCF within a local authority in South West England were approached to take part in this pilot study. Investigators visited to swab common touch-points and elevated ‘non-touch’ surfaces (>1.5m above ground level) and samples were analysed for presence of SARS-CoV-2 genetic material (RNA). Data were collected regarding LTCF infrastructure, staff behaviours, clinical and epidemiological risk factors for infection (staff and residents), and IPC measures. Criteria for success were: recruitment of three LTCF; detection of SARS-COV-2 RNA; variation in proportion of SARS-CoV-2 positive surfaces by sampling zone; and collection of clinical and epidemiological data for context. Results: Three LTCFs were recruited, ranging in size and resident demographics. Outbreaks lasted 63, 50 and 30 days with resident attack rates of 53%, 40% and 8%, respectively. The proportion of sample sites on which SARS-CoV-2 was detected was highest in rooms occupied by infected residents and varied elsewhere in the LTCF, with low levels in a facility implementing enhanced IPC measures. The heterogeneity of settings and difficulty obtaining data made it unfeasible to assess association between environmental contamination and infection. A greater proportion of elevated surfaces tested positive for SARS-CoV-2 RNA than common touch-points. Conclusions: SARS-CoV-2 RNA can be detected in a variety of LTCF outbreak settings, both on common-touch items and in elevated sites out of reach. This suggests that further work is justified, to assess feasibility and utility of environmental sampling for infection surveillance in LTCF.

A lesson identified from the COVID-19 pandemic is that we need to extend existing best practice for intervention development. In particular, we need to integrate (a) state-of-the-art methods of rapidly coproducing public health interventions and messaging to support all population groups to protect themselves and their communities with (b) methods of rapidly evaluating co-produced interventions to determine which are acceptable and effective. This paper describes the Agile Co-production and Evaluation (ACE) framework, which is intended to provide a focus for investigating new ways of rapidly developing effective interventions and messaging by combining co-production methods with large-scale testing and/or real-world evaluation. We briefly review some of the participatory, qualitative and quantitative methods that could potentially be combined and propose a research agenda to further develop, refine and validate packages of methods in a variety of public health contexts to determine which combinations are feasible, cost-effective and achieve the goal of improving health and reducing health inequalities.

IntroductionPlace-based public health evaluations are increasingly making use of natural experiments. This scoping review aimed to provide an overview of the design and use of natural experiment evaluations (NEEs), and an assessment of the plausibility of the as-if randomization assumption.MethodsA systematic search of three bibliographic databases (Pubmed, Web of Science and Ovid-Medline) was conducted in January 2020 to capture publications that reported a natural experiment of a place-based public health intervention or outcome. For each, study design elements were extracted. An additional evaluation of as-if randomization was conducted by 12 of this paper's authors who evaluated the same set of 20 randomly selected studies and assessed ‘as-if ' randomization for each.Results366 NEE studies of place-based public health interventions were identified. The most commonly used NEE approach was a Difference-in-Differences study design (25%), followed by before-after studies (23%) and regression analysis studies. 42% of NEEs had likely or probable as-if randomization of exposure (the intervention), while for 25% this was implausible. An inter-rater agreement exercise indicated poor reliability of as-if randomization assignment. Only about half of NEEs reported some form of sensitivity or falsification analysis to support inferences.ConclusionNEEs are conducted using many different designs and statistical methods and encompass various definitions of a natural experiment, while it is questionable whether all evaluations reported as natural experiments should be considered as such. The likelihood of as-if randomization should be specifically reported, and primary analyses should be supported by sensitivity analyses and/or falsification tests. Transparent reporting of NEE designs and evaluation methods will contribute to the optimum use of place-based NEEs.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex. Methods Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed “routine clinical measures”. Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1. Results The “routine clinical measures” model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The “routine clinical measures” model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents’ assumption, was the “routine clinical measures” model. However, the net benefit was marginal (0.0054 [0.0034–0.0075]). Conclusion In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level.

Abstract Background Engagement in multiple substance use risk behaviours such as tobacco smoking, alcohol and drug use during adolescence can result in adverse health and social outcomes. The impact of interventions that address multiple substance use risk behaviours, and the differential impact of universal versus targeted approaches, is unclear given findings from systematic reviews have been mixed. Our objective was to assess effects of interventions targeting multiple substance use behaviours in adolescents. Methods Eight databases were searched to October 2019. Individual and cluster randomised controlled trials were included if they addressed two or more substance use behaviours in individuals aged 8-25 years. Data were pooled in random-effects meta-analyses, reported by intervention and setting. Quality of evidence was assessed using GRADE. Heterogeneity was assessed using between-study variance, τ2 and Ι 2, and the p-value of between-study heterogeneity statistic Q. Sensitivity analyses were undertaken using the highest and lowest intra-cluster correlation coefficient (ICC). Results Of 66 included studies, most were universal (n=52) and school-based (n=41). We found moderate quality evidence that universal school-based interventions are likely to have little or no short-term benefit (up to 12 months) in relation to alcohol use (OR 0.94, 95% CI: 0.84, 1.04), tobacco use (OR 0.98, 95% CI: 0.83, 1.15), cannabis use (OR 1.06, 95% CI: 0.86, 1.31) and other illicit drug use (OR 1.09, 95% CI: 0.85, 1.39). For targeted school-level interventions, there was low quality evidence of no or a small short-term benefit: alcohol use (OR 0.90, 95% CI: 0.74-1.09), tobacco use (OR 0.86, 95% CI: 0.66, 1.11), cannabis use (OR 0.84, 95% CI: 0.66-1.07) and other illicit drug use (OR 0.79, 95% CI 0.62-1.02). There were too few family-level (n=4), individual-level (n=2) and combination level (n=5) studies to draw confident conclusions. Sensitivity analyses of ICC did not change results. Conclusions There is low to moderate quality evidence that universal and targeted school-level interventions have no or a small beneficial effect for preventing substance use multiple risk behaviours in adolescents. Higher quality trials and study reporting would allow better evidence syntheses, which is needed given small benefit of universal interventions can have high public health benefit. Trial registration Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD011374. DOI: 10.1002/14651858.CD011374.

Introduction Non-alcoholic fatty liver disease is the most common chronic liver disease worldwide affecting 20%–25% in the USA and Europe with a 60%–80% lifetime prevalence for people with type 2 diabetes (T2D). Fibrosis has repeatedly been demonstrated to be the major determinant of liver disease morbidity and mortality and there is currently no routine screening for liver fibrosis in at-risk T2D population.Methods and analysis This 12-month prospective cohort study of automated fibrosis testing uses the fibrosis-4 score (FIB-4) in patients with T2D linked to the investigation of hospital-based versus community-based second-tier transient elastography (TE) testing. We plan to include >5000 participants across 10 General Practitioner (GP) practices in East London and Bristol. This will determine the rate of undiagnosed significant liver fibrosis in a T2D population, the feasibility of two-tier liver fibrosis screening using FIB-4 at the diabetes annual review and subsequent TE delivered either in the community or secondary care settings. This will include an intention-to-treat analysis for all those invited to attend for diabetes annual review. A qualitative substudy regarding the acceptability of the fibrosis screening pathway will comprise semistructured interviews/focus groups with primary care staff (GPs and practice nurses), and patients taking part in the wider study.Ethics and dissemination This study received a favourable opinion from the Cambridge East research ethics committee. The results of this study will be disseminated in peer-reviewed scientific journals, conference presentations and local diabetes lay panel meetings.Trial registration number ISRCTN14585543.

Abstract Background Glassware can be an effective vehicle to recruit customers, revive brands, build profits and increase alcohol consumption by capitalising on the immediacy of glassware to the point of consumption. The design of glassware can also contribute to harm reduction by slowing and reducing consumption. Nucleated bases have been added to lager glasses in recent years which allow carbon dioxide (CO2) to be more rapidly released and ascend through the solution. The aim of these studies was to investigate the effect of nucleated glasses on the likeability and drinking rate of lager in alcohol drinkers. Methods In Study 1, participants (n = 116) were asked to taste two glasses of lager (280 millilitres (ml) each) in separate 5-min taste tests and fill out a likeability questionnaire after each glass in a within-subjects design with one factor of glass (nucleated, non-nucleated). The primary outcome was the likeability of lager and the secondary outcome was volume consumption during taste tests. In Study 2, participants (n = 160) were asked to consume a pint of lager (568 ml) and fill out a likeability questionnaire in a between-subjects design with one factor of glass (nucleated, non-nucleated). The primary outcome was time taken to consume a pint of lager and secondary outcomes were the likeability of lager, mood and alcohol craving. Results There was no clear evidence that likeability of lager differed between nucleated and non-nucleated glasses in either study. In Study 1, a paired-samples t test found strong evidence that lager in nucleated glasses was more visually appealing (single item from likeability measure) than lager in non-nucleated glasses (mean difference (MD) = 10.2, 95% confidence interval (CI) 6.1, 14.2, p

Plain English summary In England, young people are offered the human papillomavirus (HPV) vaccine in schools at age 12–13 years to prevent some types of cancer. Some young people have unanswered questions which may stop them getting vaccinated. We report how we developed a lesson about the HPV vaccine jointly with young people and professionals to improve how information about the HPV vaccine is given. First, we reviewed research studies and HPV vaccine information materials designed for young people. Then, we carried out interviews and workshops to ask about the best way to give a lesson and the most important information to include. We worked with creative designers to produce films and animations. Finally, we asked young people and professionals for feedback on the lesson materials. The lesson includes a PowerPoint presentation with five films and guidance for people leading the session. Key topics about the HPV vaccine to be covered were identified by young people. These included information about how vaccines work and ways to improve young people’s experience of having the HPV vaccine at school. We made changes to the information in the lesson to ensure that it was relevant to young people. We are now carrying out a study to find out how well the lesson is given and whether it can help more young people get the HPV vaccine if they want it.

Abstract Background The aim of this work was to explore barriers and facilitators to uptake of COVID-19 vaccines and to explore views and reactions to efforts to improve vaccine uptake among vaccine hesitant individuals. Methods Semi-structured interviews were conducted with people between the age of 18–29 years who had not had a COVID-19 vaccine, and those between 30 and 49 years who had not had a second dose of a COVID-19 vaccine. Results A total of 70 participants took part in the study, 35 participants had received one dose, and 35 had not been vaccinated. Participants described a willingness to be vaccinated to keep themselves and those around them safe and to avoid restrictions. Barriers to uptake included: (1) perceived lack of need for COVID-19 vaccinations, (2) concerns about the efficacy of vaccinations, (3) concerns about safety, and (4) access issues. Uptake appeared to be influenced by age and health status, trust in government, and knowledge and understanding of science. Introduction of vaccine passes may provide a motive for having a vaccine but may be viewed as coercive. Conclusion Participants were hesitant, rather than opposed, and had questions about their need for, and the safety and efficacy of the vaccine. Young people did not consider themselves to be at risk of becoming ill from COVID-19, did not think the vaccination was effective in preventing transmission, and did not think sufficient research had been conducted regarding possible long-term side-effects. Concerns were exacerbated by a lack of trust in government, and misunderstanding of science. To promote uptake, public health campaigns should focus on the provision of information from trusted sources that explains the benefits of vaccination and addresses safety concerns more effectively. To overcome inertia in people with low levels of motivation to be vaccinated, appointments must be easily accessible.

IntroductionAntibiotic resistance (ABR) has substantial global public health concerns. This systematic review aimed to synthesise recent evidence estimating the economic burden of ABR, characterised by study perspectives, healthcare settings, study design, and income of the countries.MethodsThis systematic review included peer-reviewed articles from PubMed, Medline, and Scopus databases, and grey literature on the topic of the economic burden of ABR, published between January 2016 and December 2021. The study was reported in line with 'Preferred Reporting Items for Systematic Review and Meta-Analysis' (PRISMA). Two reviewers independently screened papers for inclusion first by title, then abstract, and then the full text. Study quality was assessed using appropriate quality assessment tools. Narrative synthesis and meta-analyses of the included studies were conducted.ResultsA total of 29 studies were included in this review. Out of these studies, 69% (20/29) were conducted in high-income economies and the remainder were conducted in upper-and-middle income economies. Most of the studies were conducted from a healthcare or hospital perspective (89.6%, 26/29) and 44.8% (13/29) studies were conducted in tertiary care settings. The available evidence indicates that the attributable cost of resistant infection ranges from -US$2,371.4 to +US$29,289.1 (adjusted for 2020 price) per patient episode; the mean excess length of stay (LoS) is 7.4 days (95% CI: 3.4-11.4), the odds ratios of mortality for resistant infection is 1.844 (95% CI: 1.187-2.865) and readmission is 1.492 (95% CI: 1.231-1.807).ConclusionRecent publications show that the burden of ABR is substantial. There is still a lack of studies on the economic burden of ABR from low-income economies, and lower-middle-income economies, from a societal perspective, and in relation to primary care. The findings of this review may be of value to researchers, policymakers, clinicians, and those who are working in the field of ABR and health promotion.Systematic review registrationCRD42020193886.

Abstract Background Adolescent multiple risk behaviour (MRB) is associated with negative outcomes such as police arrests, unemployment and premature mortality and morbidity. What is unknown is whether MRB is associated with socioeconomic status (SES) in adulthood. We test whether adolescent MRB is associated with socioeconomic status (SES) in young adulthood and whether it is moderated by early life SES variables. Methods Prospective cohort studies; British Cohort Study 1970 (BCS70) and Avon Longitudinal Study of Parents and Children (ALSPAC), born in 1991–1992, were used and two comparable MRB variables were derived. Logistic regression was used to determine the association between MRB and young adult SES. The moderating effect of three early life SES variables was assessed using logistic regression models with and without interaction parameters. Evidence to support the presence of moderation was determined by likelihood ratio tests ≤p = 0.05. Multiple imputation was used to account for missing data. Results Adolescents had a median of two risk behaviours in BCS70 and three in ALSPAC. Adolescent MRB was negatively associated with young adult SES (university degree attainment) in BCS70 (OR 0.81, 95% CI: 0.76, 0.86) and ALSPAC (OR 0.85, 95% CI: 0.82, 0.88). There was a dose response relationship, with each additional risk behaviour resulting in reduced odds of university degree attainment. MRB was associated occupational status at age 34 in BCS70 (OR 0.86 95% CI: 0.82, 0.90). In BCS70, there was evidence that maternal education (p = 0.03), parental occupational status (p = 0.009) and household income (p = 0.03) moderated the effect of adolescent MRB on young adult SES in that the negative effect of MRB is stronger for those with low socioeconomic backgrounds. No evidence of moderation was found in the ALSPAC cohort. Conclusions Adolescence appears to be a critical time in the life course to address risk behaviours, due to the likelihood that behaviours established here may have effects in adulthood. Intervening on adolescent MRB could improve later SES outcomes and thus affect health outcomes later in life. Evidence for a moderation effect in the BCS70 but not ALSPAC suggests that more detailed measures should be investigated to capture the nuance of contemporary young adult SES.

Objectives There are critical periods of mortality risk at onset and cessation of opioid agonist treatment. We aim to determine whether non-fatal overdose followed the same pattern as fatal overdose, comparing the first 4 weeks of treatment and treatment cessation and the remainder time off treatment, with the remainder treatment time, to determine intervention markers. Approach Retrospective cohort study of people with a history of opioid agonist treatment using linked New South Wales data. The incidence of non-fatal overdose hospitalization; emergency department presentation; and fatal overdose from national death records were compared. Rates were calculated using generalized estimating equations adjusting for demographics, year, and recent health and incarceration events. Results The rate of an emergency department drug overdose presentation was highest. It was more than three-fold the rate of opioid non-fatal overdose hospitalisation and 14 times higher than fatal opioid overdose. It was also twice the rate of non-opioid non-fatal overdose hospitalisation. Fatal overdose was lowest while in treatment. This differed from the measures of non-fatal overdose, the overdose rate was elevated in the first four weeks in treatment as well as the first four weeks post treatment. Conclusions Retention on opioid agonist treatment is protective against drug related overdose. There is elevated risk of non-fatal overdose at treatment initiation that is not evident for fatal overdose, however the first month of treatment cessation is a critical period for both non-fatal and fatal overdose. These findings emphasize the importance of treatment retention and interventions for polysubstance overdose at cessation.

Background Injecting-related bacterial and fungal infections are associated with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. Methods and findings Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants’ index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. Conclusions Following hospitalizations with injection drug use–associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder. Thomas Brothers and co-workers study health outcomes in people with injection drug use-associated infections receiving opioid agonist treatment. Author summary Why was this study done? Injecting-related bacterial and fungal infections are an increasingly common cause of pain, disability, and death among people who inject drugs (PWID). Treatment of injecting-related infections has tended to focus on antimicrobial therapy and/or surgery, without addressing underlying substance use-related needs. Opioid agonist treatment (OAT; including methadone and buprenorphine) has been associated with decreased risks of other injecting-related health harms (including HIV infection, hepatitis C virus infection, and overdose death) and may be associated with reduced risks of recurrence after injecting-related infections. What did the researchers do and find? We identified 8,943 people with opioid use disorder who were admitted to hospital with injecting-related infections in New South Wales, Australia, between 2001 and 2018. We found that use of OAT after hospital discharge was associated with both lower risks of death and of rehospitalization with injecting-related infections. Death and rehospitalization with injecting-related infections were common, even among study participants using OAT. What do these findings mean? OAT should be considered as part of a multicomponent treatment strategy for injecting-related infections, aiming to reduce death and reinfection.

Poor quality urban environments substantially increase non-communicable disease. Responsibility for associated decision-making is dispersed across multiple agents and systems: fast growing urban authorities are the primary gatekeepers of new development and change in the UK, yet the driving forces are remote private sector interests supported by a political economy focused on short-termism and consumption-based growth. Economic valuation of externalities is widely thought to be fundamental, yet evidence on how to value and integrate it into urban development decision-making is limited, and it forms only a part of the decision-making landscape. Researchers must find new ways of integrating socio-environmental costs at numerous key leverage points across multiple complex systems. This mixed-methods study comprises of six highly integrated work packages. It aims to develop and test a multi-action intervention in two urban areas: one on large-scale mixed-use development, the other on major transport. The core intervention is the co-production with key stakeholders through interviews, workshops, and participatory action research, of three areas of evidence: economic valuations of changed health outcomes; community-led media on health inequalities; and routes to potential impact mapped through co-production with key decision-makers, advisors and the lay public. This will be achieved by: mapping system of actors and processes involved in each case study; developing, testing and refining the combined intervention; evaluating the extent to which policy and practice changes amongst our target users, and the likelihood of impact on non-communicable diseases (NCDs) downstream. The integration of such diverse disciplines and sectors presents multiple practical/operational issues. The programme is testing new approaches to research, notably with regards practitioner-researcher integration and transdisciplinary research co-leadership. Other critical risks relate to urban development timescales, uncertainties in upstream-downstream causality, and the demonstration of impact.

Abstract Background An estimated 40% of cancer cases in the UK in 2015 were attributable to cancer risk behaviours. Tobacco smoking, alcohol consumption, obesity, and unprotected sexual intercourse are known causes of cancer and there is strong evidence that physical inactivity is associated with cancer. These cancer risk behaviours co-occur however little is known about how they pattern longitudinally across adolescence and early adulthood. Using data from ALSPAC, a prospective population-based UK birth cohort study, we explored patterns of adolescent cancer risk behaviours and their associations with cancer risk behaviours in early adulthood. Methods Six thousand three hundred fifty-one people (46.0% of ALSPAC participants) provided data on all cancer risk behaviours at one time during adolescence, 1951 provided data on all cancer risk behaviours at all time points. Our exposure measure was quartiles of a continuous score summarising cumulative exposure to cancer risk behaviours and longitudinal latent classes summarising distinct categories of adolescents exhibiting similar patterns of behaviours, between age 11 and 18 years. Using both exposure measures, odds of harmful drinking (Alcohol Use Disorders Identification Test-C ≥ 8),daily tobacco smoking, nicotine dependence (Fagerström test ≥4), obesity (BMI ≥30), high waist circumference (females: ≥80 cm and males: ≥94 cm, and high waist-hip ratio (females: ≥0.85 and males: ≥1.00) at age 24 were estimated using logistic regression analysis. Results We found distinct groups of adolescents characterised by consistently high and consistently low engagement in cancer risk behaviours. After adjustment, adolescents in the top quartile had greater odds of all outcomes in early adulthood: nicotine dependency (odds ratio, OR = 5.37, 95% confidence interval, CI = 3.64–7.93); daily smoking (OR = 5.10, 95% CI =3.19–8.17); obesity (OR = 4.84, 95% CI = 3.33–7.03); high waist circumference (OR = 2.48, 95% CI = 1.94–3.16); harmful drinking (OR = 2.04, 95% CI = 1.57–2.65); and high waist-hip ratio (OR = 1.88, 95% CI = 1.30–2.71), compared to the bottom quartile. In latent class analysis, adolescents characterised by consistently high-risk behaviours throughout adolescence were at higher risk of all cancer risk behaviours at age 24, except harmful drinking. Conclusions Exposure to adolescent cancer risk behaviours greatly increased the odds of cancer risk behaviours in early adulthood. Interventions to reduce these behaviours should target multiple rather than single risk behaviours and should focus on adolescence.

Abstract Background Natural or quasi experiments are appealing for public health research because they enable the evaluation of events or interventions that are difficult or impossible to manipulate experimentally, such as many policy and health system reforms. However, there remains ambiguity in the literature about their definition and how they differ from randomized controlled experiments and from other observational designs. We conceptualise natural experiments in the context of public health evaluations and align the study design to the Target Trial Framework. Methods A literature search was conducted, and key methodological papers were used to develop this work. Peer-reviewed papers were supplemented by grey literature. Results Natural experiment studies (NES) combine features of experiments and non-experiments. They differ from planned experiments, such as randomized controlled trials, in that exposure allocation is not controlled by researchers. They differ from other observational designs in that they evaluate the impact of events or process that leads to differences in exposure. As a result they are, in theory, less susceptible to bias than other observational study designs. Importantly, causal inference relies heavily on the assumption that exposure allocation can be considered ‘as-if randomized’. The target trial framework provides a systematic basis for evaluating this assumption and the other design elements that underpin the causal claims that can be made from NES. Conclusions NES should be considered a type of study design rather than a set of tools for analyses of non-randomized interventions. Alignment of NES to the Target Trial framework will clarify the strength of evidence underpinning claims about the effectiveness of public health interventions.

Introduction Persistent infection with HPV can result in cancers affecting men and, especially, women. Lower uptake exists by area and different population groups. Increasing parental confidence about, and adolescent access to, the universal HPV vaccination programme may help reduce inequalities in uptake. However, the evidence-base for interventions to address uptake for schools-based HPV vaccination programmes is currently lacking. This study protocol outlines how a multicomponent intervention to address this evidence gap will be codesigned with parents.Methods and analysis The proposed research will be undertaken in localities covered by two immunisation teams in London and the south-west of England. The ‘person-based approach’ to intervention development will be followed. In the first phase, an exploratory qualitative study will be undertaken with key stakeholders (n=8) and parents (n=40) who did not provide consent for their adolescent child to be vaccinated. During the interviews, parents’ views on ways to improve parental confidence about, and adolescents’ access to, HPV vaccination will be sought. The findings will be used to inform the co-design of a preliminary plan for a targeted, multicomponent intervention. In the second phase, at least two parent working groups (n=8) will be convened and will work with creative designers to co-design communication materials aimed at increasing parents’ confidence in vaccination. At least two workshops with each parent group will be organised to obtain feedback on the intervention plan and communication materials to ensure they are fit for purpose. These findings will inform a protocol for a future study to test the effectiveness of the intervention at increasing HPV vaccination uptake.Ethics and dissemination The National Health Services Research Ethics Service and London School of Hygiene & Tropical Medicine Observational / Interventions Research Ethics Committee provided approvals for the study (reference 22/SW/0003 & 26902, respectively). We will work with parent advisory groups to inform our dissemination strategy and co-present our findings (eg, at community events or through social media). We will disseminate our findings with academics and healthcare professionals through webinars and academic conferences, as well as peer-reviewed publications.

Abstract Background We need to monitor patterns of antibiotic prescribing in order to develop and evaluate antibiotic stewardship interventions in rural China. As part of a multidisciplinary study of antibiotic use in Anhui Province we assessed the validity of electronic records (e-records) as a source of surveillance data. Methods One township healthcare centre and one village clinic were selected in each of three different counties. Patients with symptoms of Upper Respiratory Tract Infection (URTI), exacerbation of Chronic Obstructive Pulmonary Disease (COPD) or Urinary Tract Infection (UTI) were recruited consecutively. Researchers observed and documented clinic consultations and interviewed each of the study participants. E-records were compared to clinic observations and patient interviews. Results A total of 1030 patients were observed in clinic. Antibiotics were prescribed in 917 (89%) of consultations. E-records were created only for individuals with health insurance, with considerable between-site variation in completeness (0 to 98.7% of clinic consultations) and in the timing of documentation (within-consultation up to weeks afterwards). E-record accuracy was better in relation to antibiotics (82.8% of e-records accurately recorded what was prescribed in clinic) than for diagnosis and symptoms (45.0 and 1.1% accuracy). Only 31 participants (3.0%) presented with UTI symptoms. Conclusions We have confirmed very high rates of outpatient antibiotic prescribing in rural Anhui province. E-records could provide useful information to inform stewardship interventions, however they may be inaccurate and/or biased. Public Health authorities should focus on improving technical infrastructure and record-keeping culture in outpatient settings. Further research is needed into community treatment of UTIs.

Abstract Background Experimentation with new behaviours during adolescence is normal. However, engagement in two or more risk behaviours, termed multiple risk behaviours is associated with socioeconomic disadvantage and poor health and social outcomes. Evidence of how adolescents cluster based on their risk behaviours is mixed. Methods Latent Class Analysis was used to study patterns of engagement in 10 self-reported risk behaviours (including substance use, self-harm and sexual health) from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort at ages 15–16 years. Data was available for 6556 adolescents. Associations between risk profile and sex were explored. Results A 3-class model for both females and males was deemed to have acceptable fit. Whilst we found evidence of a sex difference in the risk behaviours reported within each class, the sex-specific results were very similar in many respects. For instance, the prevalence of membership of the high-risk class was 8.5% for males and 8.7% for females and both groups had an average of 5.9 behaviours. However, the classes were both statistically dubious, with class separation (entropy) being poor as well as conceptually problematic, because the resulting classes did not provide distinct profiles and varied only by quantity of risk-behaviours. Conclusion Clusters of adolescents were not characterised by distinct risk behaviour profiles, and provide no additional insight for intervention strategies. Given this is a more complicated, software-specific method, we conclude that an equally effective, but more readily replicable approach is to use a count of the number of risk behaviours.

Abstract Background Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders. Methods cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively. Discussion The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

Summary: Background: In many countries, the average age of people who use illicit opioids, such as heroin, is increasing. This has been suggested to be a reason for increasing numbers of opioid-related deaths seen in surveillance data. We aimed to describe causes of death among people who use illicit opioids in England, how causes of death have changed over time, and how they change with age. Methods: In this matched cohort study, we studied patients in the Clinical Practice Research Datalink with recorded illicit opioid use (defined as aged 18–64 years, with prescriptions or clinical observations that indicate use of illicit opioids) in England between Jan 1, 2001, and Oct 30, 2018. We also included a comparison group, matched (1:3) for age, sex, and general practice with no records of illicit opioid use before cohort entry. Dates and causes of death were obtained from the UK Office for National Statistics. The cohort exit date was the earliest of date of death or Oct 30, 2018. We described rates of death and calculated cause-specific standardised mortality ratios. We used Poisson regression to estimate associations between age, calendar year, and cause-specific death. Findings: We collected data for 106 789 participants with a history of illicit opioid use, with a median follow-up of 8·7 years (IQR 4·3–13·5), and 320 367 matched controls with a median follow-up of 9·5 years (5·0–14·4). 13 209 (12·4%) of 106 789 participants in the exposed cohort had died, with a standardised mortality ratio of 7·72 (95% CI 7·47–7·97). The most common causes of death were drug poisoning (4375 [33·1%] of 13 209), liver disease (1272 [9·6%]), chronic obstructive pulmonary disease (COPD; 681 [5·2%]), and suicide (645 [4·9%]). Participants with a history of illicit opioid use had higher mortality rates than the comparison group for all causes of death analysed, with highest standardised mortality ratios being seen for viral hepatitis (103·5 [95% CI 61·7–242·6]), HIV (16·7 [9·5–34·9]), and COPD (14·8 [12·6–17·6]). In the exposed cohort, at age 20 years, the rate of fatal drug poisonings was 271 (95% CI 230–313) per 100 000 person-years, accounting for 59·9% of deaths at this age, whereas the mortality rate due to non-communicable diseases was 31 (16–45) per 100 000 person-years, accounting for 6·8% of deaths at this age. Deaths due to non-communicable diseases increased more rapidly with age (1155 [95% CI 880–1431] deaths per 100 000 person-years at age 50 years; accounting for 52·0% of deaths at this age) than did deaths due to drug poisoning (507 (95% CI 452–562) per 100 000 person-years at age 50 years; accounting for 22·8% of deaths at this age). Mirroring national surveillance data, the rate of fatal drug poisonings in the exposed cohort increased from 345 (95% CI 299–391) deaths per 100 000 person-years in 2010–12 to 534 (468–600) per 100 000 person-years in 2016–18; an increase of 55%, a trend that was not explained by ageing of participants. Interpretation: People who use illicit opioids have excess risk of death across all major causes of death we analysed. Our findings suggest that population ageing is unlikely to explain the increasing number of fatal drug poisonings seen in surveillance data, but is associated with many more deaths due to non-communicable diseases. Funding: National Institute for Health Research.

Summary: Background: A considerable proportion of people who inject drugs are unstably housed. Although unstable housing is associated with HIV and HCV infection among people who inject drugs, its contribution to transmission is unknown. We estimated the global and national proportions of incident HIV and HCV infections among people who inject drugs attributed to housing instability from 2020 to 2029. Methods: In this modelling study, we developed country-level models of unstable housing and HIV and HCV transmission among people who inject drugs in 58 countries globally, calibrated to country-specific data on the prevalences of HIV and HCV and unstable housing. Based on a recently published systematic review, unstably housed people who inject drugs were assumed to have a 39% (95% CI 6–84) increased risk of HIV transmission and a 64% (95% CI 43–89%) increased risk of HCV transmission. We used pooled country-level estimates from systematic reviews on HCV and HIV prevalence in people who inject drugs. Our models estimated the transmission population attributable fraction (tPAF) of unstable housing to HIV and HCV transmission among people who inject drugs, defined as the percentage of infections prevented from 2020 to 2029 if the additional risk due to unstable housing was removed. Findings: Our models were produced for 58 countries with sufficient data (accounting for >66% of the global people who inject drugs population). Globally, we project unstable housing contributes 7·9% (95% credibility interval [CrI] 2·3–15·7) of new HIV infections and 11·2% (7·7–15·5) of new HCV infections among people who inject drugs from 2020 to 2029. Country-level tPAFs were strongly associated with the prevalence of unstable housing. tPAFs were greater in high-income countries (HIV 17·2% [95% CrI 5·1–30·0]; HCV 19·4% [95% CrI 13·8–26·0]) than in low-income or middle-income countries (HIV 6·6% [95% CrI 1·8–13·1]; HCV 8·3% [95% CrI 5·5–11·7]). tPAFs for HIV and HCV were highest in Afghanistan, Czech Republic, India, USA, England, and Wales where unstable housing contributed more than 20% of new HIV and HCV infections. Interpretation: Unstable housing is an important modifiable risk factor for HIV and HCV transmission among people who inject drugs in many countries. The study emphasises the importance of implementing initiatives to mitigate these risks and reduce housing instability. Funding: National Institute for Health Research and National Institute of Allergy and Infectious Diseases and National Institute for Drug Abuse.

Background and aimsThis qualitative study aimed to explore how the development of tolerance to both the psychoactive and respiratory depressant effects of heroin on re-exposure are experienced by people who use heroin.MethodsSemi-structured one-to-one interviews were conducted with 20 adults who currently or previously used heroin (for at least 6 months), with any type of administration (injected, smoked) and experience of abstinence (at least 2 weeks) and relapse. Topic guides explored the participants understanding of tolerance, their experience of developing tolerance to heroin and of tolerance following relapse. Interviews were audio-recorded and transcribed. Thematic analysis was used to generate salient themes.ResultsThe analysis produced three broad themes: lay understanding of tolerance; tolerating tolerance; and rapid tolerance development following relapse. Tolerance was defined as the body adapting to regular drug use, so that the drug no longer produced the same level of effect. Tolerance was experienced as interacting and co-developing with physical dependence and the symptoms of withdrawal. Indeed, several participants did not differentiate between tolerance and dependence. Most participants did not notice tolerance to respiratory depression. Tolerance levels fluctuated-increasing over periods of regular use and reducing when abstinent. Using more drug was the most common response to increasing tolerance to the desired effects. On re-use following abstinence, tolerance was experienced as developing more quickly in the most recent relapse compared to the first. Tolerance was also perceived to return more quickly with each abstinence-relapse cycle.ConclusionsQualitative accounts of tolerance report that tolerance returns more quickly with each relapse episode. By elucidating the mechanism(s) involved and potentially discovering how they could be switched on prior to relapse occurring we might be able to develop a beneficial harm reduction treatment for people in abstinence that would protect against overdose occurring on subsequent relapse.

Background: Digital interventions have the potential to reduce alcohol consumption, although evidence on the effectiveness of apps is lacking. Drink Less is a popular, evidence-informed app with good usability, putting it in a strong position to be improved upon prior to conducting a confirmatory evaluation. This paper describes the process of refining Drink Less to improve its usability and likely effectiveness. Methods: The refinement consisted of three phases and involved qualitative and quantitative (mixed) methods: i) identifying changes to app content, based on findings from an initial evaluation of Drink Less, an updated review of digital alcohol interventions and a content analysis of user feedback; ii) designing new app modules with public input and a consultation with app developers and researchers; and iii) improving the app’s usability through user testing. Results: As a result of the updated review of digital alcohol interventions and user feedback analysis in Phase 1, three new modules: ‘Behaviour Substitution’, ‘Information about Antecedents’ and ‘Insights’, were added to the app. One existing module – ‘Identity Change’ – was removed based on the initial evaluation of Drink Less. Phases 2 and 3 resulted in changes to existing features, such as improving the navigational structure and onboarding process, and clarifying how to edit drinks and goals. Conclusions: A mixed methods approach was used to refine the content and design of Drink Less, providing insights into how to improve its usability and likely effectiveness. Drink Less is now ready for a confirmatory evaluation.

Objectives: Young people are considered at lower risk from coronavirus disease-19 (COVID-19). However, measures to limit the population health impact of the current COVID-19 pandemic have caused significant disruptions to their lives. The objective of this study was to explore the experiences of young people predominantly living in the south-west of England during the COVID-19 pandemic. Study design: Rapid qualitative study. Methods: Following advertisement on social media, a purposive sample of young people by age and gender who had expressed an interest were invited to participate. In June 2020, 21 young people (12–17 years) took part in 18 semi-structured interviews, either through a digital platform or by telephone. Interviews were recorded digitally and transcribed verbatim. Thematic analysis was undertaken, assisted by NVvivo Software. Results: Young people felt the greatest impacts of the pandemic have been disruption to how they learned because of school closures and limited face-to-face interaction with their social networks. There was variation in terms of how satisfied young people were with self-directed learning at home, and some anxieties in relation to its effectiveness outside the school environment. Most young people reported maintaining social relationships remotely, but some young people appeared to have little social interaction outside their household. High levels of adherence to social distancing and handwashing were reported, which could lead to a sense of injustice resulting from visibility of other people breaching social distancing guidance. Young people were willing to be vaccinated against COVID-19 if a vaccine became available, with the greatest motivator being to protect others above themselves. Conclusions: Young people have experienced significant disruption to their education and social networks during the COVID-19 pandemic. During lockdown, high levels of compliance to government public health guidelines to reduce transmission of COVID-19 were reported by young people. If an effective vaccine is developed, a schools-based vaccination programme could be an efficient method to interrupt transmission to more at-risk populations and prevent further disruptions to young people's education.

Objectives To test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new policy providing additional opportunities to consent.Setting Two local authorities in the south-west of England.Participants Young women (n=7129) routinely eligible for HPV vaccination aged 12–13 years during the intervention period (2017/2018 to 2018/2019 programme years).Interventions Local policy change that included additional opportunities to provide consent (parental verbal consent and adolescent self-consent).Outcomes Secondary analyses of cross-sectional intervention data were undertaken to examine uptake by: (1) receipt of parental written consent forms and; (2) percentage of unvaccinated young women by stage of implementation.Results During the intervention period, 6341 (89.0%) eligible young women initiated the HPV vaccination series. Parental written consent forms were less likely to be returned where young women attended alternative education provider settings (p

Summary: A need exists to accurately estimate overdose risk and improve understanding of how to deliver treatments and interventions in people with opioid use disorder in a way that reduces such risk. We consider opportunities for predictive analytics and routinely collected administrative data to evaluate how overdose could be reduced among people with opioid use disorder. Specifically, we summarise global trends in opioid use and overdoses; describe the use of big data in research into opioid overdose; consider the potential for predictive modelling, including machine learning, for prevention and monitoring of opioid overdoses; and outline the challenges and risks relating to the use of big data and machine learning in reducing harms that are related to opioid use. Future research for improving the coverage and provision of existing interventions, treatments, and resources for opioid use disorder requires collaboration of multiple agencies. Predictive modelling could transport the concept of stratified medicine to public health through novel methods, such as predictive modelling and emulated trials for evaluating diagnoses and prognoses of opioid use disorder, predicting treatment response, and providing targeted treatment recommendations.

Background: SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy. Methods: In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices. Findings: We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19TM device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations (“spectrum effects”), but the extent of this varied by device. Interpretation: The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives. Funding: Public Health England.

Background: Digital interventions have the potential to reduce alcohol consumption, although evidence on the effectiveness of apps is lacking. Drink Less is a popular, evidence-informed app with good usability, putting it in a strong position to be improved upon prior to conducting a confirmatory evaluation. This paper describes the process of refining Drink Less to improve its usability and likely effectiveness. Methods: The refinement consisted of three phases and involved qualitative and quantitative (mixed) methods: i) identifying changes to app content, based on findings from an initial evaluation of Drink Less, an updated review of digital alcohol interventions and a content analysis of user feedback; ii) designing new app modules with public input and a consultation with app developers and researchers; and iii) improving the app’s usability through user testing. Results: As a result of the updated review of digital alcohol interventions and user feedback analysis in Phase 1, three new modules: ‘Behaviour Substitution’, ‘Information about Antecedents’ and ‘Insights’, were added to the app. One existing module – ‘Identity Change’ – was removed based on the initial evaluation of Drink Less. Phases 2 and 3 resulted in changes to existing features, such as improving the navigational structure and onboarding process, and clarifying how to edit drinks and goals. Conclusions: A mixed methods approach was used to refine the content and design of Drink Less, providing insights into how to improve its usability and likely effectiveness. Drink Less is now ready for a confirmatory evaluation.