Development, acceptability and feasibility of a personalised, behavioural intervention to prevent bacterial skin and soft tissue infections among people who inject drugs: a mixed-methods Person-Based Approach study.

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.

Engineering CpG island DNA methylation in pluripotent cells through synthetic CpG-free ssDNA insertion.

Cellular differentiation requires global changes to DNA methylation (DNAme), where it functions to regulate transcription factor, chromatin remodeling activity, and genome interpretation. Here, we describe a simple DNAme engineering approach in pluripotent stem cells (PSCs) that stably extends DNAme across target CpG islands (CGIs). Integration of synthetic CpG-free single-stranded DNA (ssDNA) induces a target CpG island methylation response (CIMR) in multiple PSC lines, Nt2d1 embryonal carcinoma cells, and mouse PSCs but not in highly methylated CpG island hypermethylator phenotype (CIMP)+ cancer lines. MLH1 CIMR DNAme spanned the CGI, was precisely maintained through cellular differentiation, suppressed MLH1 expression, and sensitized derived cardiomyocytes and thymic epithelial cells to cisplatin. Guidelines for CIMR editing are provided, and initial CIMR DNAme is characterized at TP53 and ONECUT1 CGIs. Collectively, this resource facilitates CpG island DNAme engineering in pluripotency and the genesis of novel epigenetic models of development and disease.

Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): A qualitative study of experiences of COVID-19 among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour. METHODS: Telephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis. RESULTS: Concern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to 'stay home' led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources. CONCLUSION: This study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services.

Detachable low dead space syringes for the prevention of hepatitis C among people who inject drugs in Bristol, UK: an economic evaluation.

BACKGROUND AND AIMS: Traditional detachable syringes used by people who inject drugs (PWID) retain larger volumes of blood when the plunger is depressed than syringes with fixed needles-referred to as high (HDSS) and low dead space syringes (LDSS), respectively. Evidence suggests that using HDSS may result in greater hepatitis C virus (HCV) transmission risk than LDSS. We evaluated the cost-effectiveness of an intervention to introduce detachable LDSS in a needle and syringe programme (NSP). DESIGN: HCV transmission and disease progression model with cost-effectiveness analysis using a health-care perspective. Detachable LDSS are associated with increased costs (£0.008) per syringe, yearly staff training costs (£536) and an estimated decreased risk (by 47.5%) of HCV transmission compared with HDSS. The intervention was modelled for 10 years, with costs and health benefits (quality-adjusted life-years: QALYs) tracked over 50 years. SETTING: Bristol, UK. PARTICIPANTS AND CASES: PWID attending NSP. INTERVENTION AND COMPARATOR: Gradual replacement of HDSS at NSP, with 8, 58 and 95% of HDSS being replaced by detachable LDSS in 2016, 2017 and 2018, respectively. Comparator was continuing use of HDSS. MEASUREMENTS: Net monetary benefit. Benefits were measured in QALYs. FINDINGS: Introducing detachable LDSS was associated with a small increase in intervention costs (£21 717) compared with not introducing detachable LDSS, but considerable savings in HCV-related treatment and care costs (£4 138 118). Overall cost savings were £4 116 401 over 50 years and QALY gains were 1000, with an estimated 30% reduction in new infections over the 10-year intervention period. In all sensitivity analyses, detachable LDSS resulted in cost savings and additional QALYs. Threshold analyses suggested that detachable LDSS would need to reduce HCV transmission risk of HDSS by 0.26% to be cost-saving and 0.04% to be cost-effective. CONCLUSIONS: Replacing high dead space syringes with detachable low dead space syringes in needle and syringe programmes in the United Kingdom is likely to be a cost-saving approach for reducing hepatitis C virus transmission.

Co-design of harm reduction materials for people who inject drugs to implement research findings.

BACKGROUND: Equipment used by people who inject drugs (PWID) either has a needle which is fixed to the syringe or can be detached and replaced. Detachable low dead space syringes (LDSS) have been developed, with less space between the needle and plunger (referred to as dead space) than traditional detachable equipment. This equipment can help protect PWID from harm of infection as less blood is transferred if equipment is shared. Our previous research found that detachable LDSS are likely to be acceptable to PWID, and we produced recommendations for their introduction in needle and syringe programmes (NSP) in the United Kingdom (UK). We held a national stakeholder meeting to discuss how to accelerate the pace and scale of the rollout and uptake of detachable LDSS. This commentary reflects on the involvement of PWID as co-designers of harm reduction materials to implement these research findings in a way that supports the uptake of LDSS equipment by NSP and service users. We present the user-centred design process, peer reflections on the project, and lessons learnt by the team working with the peers. MAIN BODY: Peers and stakeholders translated the research into easy to understand messages following a consultation with NSP across the UK. Working with Linnell Publications over three workshops, peers selected their preferred design style and informed the language, messages, and overall look of the designs. The peers ensured the designs avoided images and language with negative connotations, humour, and unequivocal language. Peers said that they found the process enjoyable and informative-leading to increased awareness of harm reduction practices. The facilitators took steps to ensure the views of the peers were heard throughout. They reflected on the importance of involving PWID meaningfully throughout the project. Without the peers, the designs would be less effective and engaging to their target audience. CONCLUSION: We conclude that placing peers at the heart of this research implementation project was essential to ensure the materials are appropriate and engaging and do not stigmatise or alienate the intended audience unintentionally. We recommend that others planning similar work include peers within the entire project to support their meaningful contribution.