Title: Promoting skin and soft tissue infection care and preventing AA-amyloidosis renal failure among people who inject drugs in the United Kingdom: A mixed methods multi-phase study.
Funder: Department of Health and Social Care

Abstract: Background Skin and soft tissue infections (SSTI) are a significant cause of morbidity and mortality among people who inject drugs (PWID) in the UK. Complications associated with SSTI include sepsis, gangrene, endocarditis and AA-amyloidosis; these can lead to limb amputation, renal failure and death. Up to 60% of PWID in the UK report symptoms of recent or current SSTI, with 10% reporting SSTI-related hospital admissions per year. The majority of hospitalisations are avoidable, and are due to delays in primary care access. Despite the high individual and societal burden of injecting-related SSTI, it is a poorly understood and under-researched condition in the UK. AA-amyloidosis is a serious sequela of chronic SSTI among PWID. Left untreated it can lead to renal failure and premature mortality. Inequalities in outcome are pronouced: PWID median survival rate is 19 months compared to 52 months for all patients with AA-amyloidosis on haemodialysis in the UK. Symptoms of AA-amyloidosis can be subtle; renal failure and death can occur prior to detection. This is a preventable and potentially reversible condition. Disease progression can be arrested with prompt and effective SSTI treatment alongside injecting cessation. AA-amyloidosis screening involves simple urinalysis, yet this has not been implemented in any UK drug treatment services. Aim To improve SSTI prevention, care and treatment interventions for PWID, including through assessing the feasibility of screening, diagnosis and treatment referral for AA-amyloidosis in UK drug treatment services. Plan of investigationThis program of work employs a mixed-methods multi-phase design, comprising five interlinked phases in four sites (Camden South and North, Turning Point Croydon and Medway): Phase1) Determining the evidence base through systematic literature review of SSTI interventions for PWID. Phase2) Assessing the feasibility of AA-amyloidosis screening, diagnostic and treatment referral in drug treatment services through: patient and provider workshops (n=8); provider-administered SSTI survey and protenuira urinalysis with PWID clients; referral to specialist services; peer accompaniment to daignostic appointment. Phase3) Delineating the barriers and facilitators to the AA-amyloidosis care pathway through qualitative longitudinal study (n=~15 at baseline) using in-depth interviews and observations before, at the time of, and 3-4 months after, specialist referral. Phase4) Exploring the factors that inform SSTI protection and risk through a qualitative case-control study using in-depth interviews with an age and injecting-history matched sample of PWID with, and without SSTI (n=45-50). Phase 5) Collaboratively developing information resources and educational videos through workshops with PWID (n=4). Resources will be informed by data generated from phases 1-4 and evaluated through PWID focus groups (n=3). Patient and NHS benefits Outcomes include: the dissemination of educational resources developed in collaboration with the affected community; recommendations for the development and implementation of SSTI interventions; recognition of AA-amyloidosis as a health concern; the development of a national AA-amyloidosis screening study in collaboration with Public Health England (dependant on feasibility study outcomes). The project has cost saving implications. Injecting-related SSTI NHS costs are in the region of 77 million annually. Intensive care admission is common, due to delays in primary care access. Early intervention for AA-amyloidosis has the potential to save lives and reduce dialysis costs of 31,000 per-person annually. Benefits have transferability to other populations and conditions. Understanding barriers and facilitators to the AA-amyloidosis care pathway offers insight into enabling care for other SSTI complications. Improved SSTI services provide a foundation to address addiction and other chronic health issues, such as HCV and HIV. The promotion of non-injecting routes of drug administration can avert early mortality from AA-amyloidosis, but also overdose, viral infections and other SSTI complications. Information resources will include tailored information on antibiotic use; valuable for preventing antimicrobial resistance as well as treating SSTI.

Lay abstract: Background Skin and soft tissue infections (SSTIs) are a significant, yet under-researched, cause of illness and death among people who inject drugs (PWID) in the UK. Approximately 10% (~20,000) of PWID in the UK are hospitalised each year for SSTI-related problems. The majority of these hospitalisations are avoidable; due to delays in primary care access. SSTI care for PWID costs the NHS around 77 million per year. Delayed care for SSTIs can result in serious complications, with consequences such as limb amputation, renal failure and death. One poorly understood SSTI complication is AA-amyloidosis. This is a serious multi-organ condition, caused by persistent inflammation and predominantly affecting the kidneys. PWID in the UK are generally referred for assessment late, by which time they have renal failure. Dialysis or kidney transplantation are then the only treatment options. PWID can experience difficulty adhering to dialysis treatment and, in the UK, their medium survival rate is 19 months from diagnosis. This compares to 52 months for other populations. AA-amyloidosis is a preventable condition: early risk screening, regular wound-care and injecting cessation can prevent and reverse disease progression. The extent of AA-amyloidosis among PWID in the UK is unknown and no UK drug treatment services provide routine AA-amyloidosis risk screening or early intervention. Screening is simple involving a dip-stick urine test for protein and a confirmatory laboratory test. Early intervention involves information and supports for PWID to access SSTI care and stop injecting. Despite the high societal and individual burden of SSTI among PWID, no research has investigated the barriers and facilitators to SSTI health care access among PWID in the UK or the feasibility and acceptability of AA-amyloidosis screening and treatment referral. This study will fill that gap. Aim This study aims to improve SSTI prevention, care and treatment interventions for PWID, including through assessing the feasibility of screening, diagnosis and treatment referral for AA-amyloidosis in UK drug treatment services. Study sites Participants will be recruited from four drug treatment services: Camden North and South Drug Services and Turning Point Croydon and Medway. Together, the sites serve a large and diverse PWID client base. Design and methods The project involves five linked phases. Phase1. Determining the evidence: A systematic review of the UK and international literature will assess SSTI prevention and care interventions for PWID. Phase2. Screening and referral feasibility: Eight workshops with service users and providers will explore views on SSTIs and the proposed AA-amyloidosis screening intervention, also collaboratively developing patient screening information pamphlets. A urine test and risk factor survey will then be offered to all PWID at four Drug Treatment Services over a six month period (approximately 400 PWID). Those with SSTI history and high protein urine levels will be referred to the National Amyloidosis Centre for diagnostic assessment. Peer support for the day long assessment appointment will be provided. Participants will be asked if they are interested in interview follow-up. Phase3. Barriers and facilitators to care: Approximately 15 participants referred to the NAC will be followed through the care pathway. This will involve in-depth interviews: before, during and 3-4 months after diagnostic assessment. Observations of the assessment process will take place. This approach enables exploration of the barriers and facilitators to diagnostic and treatment access in context. Phase4. SSTI prevention and risk management: 45-50 PWID with, and without, SSTI will be interviewed to explore how they look after their injecting health and the factors informing SSTI risk. Insight into successful self-care practices is crucial for informing community acceptable interventions. Phase5. Resource production: This phase draws on data generated in phases 1-4 and involves workshops with PWID. Four workshops will be held (one at each site) in which study findings will be discussed and the content for SSTI and AA-amyloidosis awareness resources (one booklet and two videos) collaboratively developed. Resources will be evaluated in focus groups with service users. SignificanceThis study is innovative and holds great potential for patient benefit. It is the first in the UK to investigate the barriers and facilitators to SSTI care among PWID, and the first globally to explore the potential of urine screening in drug treatment settings for preventing SSTI-related kidney failure. The proposal has been developed in collaboration with the homelessness charity Groundswell; the National Amyloidosis Centre; Camden Drug Services; Turning Point charity and UK service user representatives. Outcomes that will benefit patients and providers include (but are not limited to): the development of SSTI and AA-amyloidosis awareness resources, indicators of AA-amyloidosis prevalence among UK PWID and intervention recommendations.

Research activity codes: 4.3 INFLUENCES AND IMPACT
Health categories: INFECTION