Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance, often treated via electrical cardioversion. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs, suggesting that defects in contractility occur in AFib and are revealed upon restoration of rhythm. This project aims to define the contractile remodeling that occurs in AFib. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. Atrial cardiomyocytes showed reduced force of contraction, decreased resting tension, and increased calcium sensitivity in skinned single cardiomyocyte studies. These alterations correlated with degradation of myofilament proteins including myosin heavy chain altering force of contraction, titin altering resting tension, and TnI altering calcium sensitivity. We measured degradation of other myofilament proteins including cMyBP-C and actininshowing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. These results provide an understanding of the contractile remodeling that occurs in AFib and provide insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.

The nexus of immigration regulation and health governance: a scoping review of the extent to which right to access healthcare by migrants, refugees and asylum seekers was upheld in the United Kingdom during COVID-19.

OBJECTIVES: Complementing the well-established evidence base on health inequalities experienced by migrants, refugees and asylum seekers in the UK; we examined the extent to which their right to equal non-discriminatory access to health services (promotive, preventive, curative) was upheld during the COVID-19 pandemic. STUDY DESIGN: Arksey and O'Malley's scoping review framework. METHODS: A comprehensive search was conducted on Medline, PubMed, and CINAHL using detailed MESH terms, for literature published between 01 January 2020 and 01 January 2024. The process was supported by a ten-page Google search and hand searching of reference lists. 42 records meeting the inclusion criteria were charted, coded inductively and analysed thematically in an integrated team-based approach. RESULTS: Dissonance between immigration regulation and health governance is illustrated in four themes: Health systems leveraged to (re)enforce the hostile environment; Dissonance between health rights on paper and in practice; Structural failures to overcome communication and digital exclusion; and COVID-19 vaccine (in)equity exacerbated fear, mistrust and exclusion. Migrants, refugees and asylum seekers encountered substantial individual, structural and policy-level barriers to accessing healthcare in the UK during COVID-19. Insecure immigration status, institutional mistrust, data-sharing and charging fears, communication challenges and digital exclusion impacted heavily on their ability to access healthcare in an equitable non-discriminatory manner. CONCLUSIONS: An inclusive and innovative health equity and rights-based responses reaching all migrants, refugees and asylum seekers are warranted if the National Health Service is to live up to its promise of 'leaving no one behind' in post-pandemic and future responses.

Has the HCV cascade of care changed among people who inject drugs in England since the introduction of direct-acting antivirals?

BACKGROUND: In England, over 80 % of those with hepatitis C virus (HCV) infection have injected drugs. We quantified the HCV cascade of care (CoC) among people who inject drugs (PWID) in England and determined whether this improved after direct-acting antivirals (DAAs) were introduced. METHODS: We analysed data from nine rounds of national annual cross-sectional surveys of PWID recruited from drug services (2011-2019; N = 12,320). Study rounds were grouped as: 'Pre-DAAs' (2011-2014), 'Prioritised DAAs' (2015-2016) and 'Unrestricted DAAs' (2017-2019). Participants were anonymously tested for HCV antibodies and RNA and completed a short survey. We assessed the proportion of PWID recently (current/previous year) tested for HCV. For participants ever HCV treatment eligible (past chronic infection with history of treatment or current chronic infection), we assessed the CoC as: HCV testing (ever), received a positive test result, seen a specialist nurse/doctor, and ever treated. We used logistic regression to determine if individuals progressed through the CoC differently depending on time-period, whether time-period was associated with recent testing (all participants) and lifetime HCV treatment (ever eligible participants), and predictors of HCV testing and treatment in the Unrestricted DAAs period. RESULTS: The proportion of ever HCV treatment eligible PWID reporting lifetime HCV treatment increased from 12.5 % in the Pre-DAAs period to 25.6 % in the Unrestricted DAAs period (aOR:2.40, 95 %CI:1.95-2.96). There were also increases in seeing a specialist nurse/doctor. The largest loss in the CoC was at treatment for all time periods. During the Unrestricted DAAs period, recent (past year) homelessness (vs never, aOR:0.66, 95 %CI:0.45-0.97), duration of injecting (≤3 years vs >3 years; aOR:0.26, 95 %CI:0.12-0.60), never (vs current, aOR:0.31, 95 %CI:0.13-0.75) or previously being prescribed OAT (vs current, aOR:0.67, 95 %CI:0.47-0.95), and never using a NSP (vs past year, aOR:0.27, 95 %CI:0.08-0.89) were negatively associated with lifetime HCV treatment. The proportion of PWID reporting recent HCV testing was higher during Unrestricted DAAs (56 %) compared to Pre-DAAs (48 %; aOR:1.28, 95 %CI:1.06-1.54). CONCLUSION: COC stages from seeing a specialist onwards improved after DAAs became widely available. Further improvements in HCV testing are needed to eliminate HCV in England.

Fine tuning contractility: atrial sarcomere function in health and disease.

The molecular mechanisms of sarcomere proteins underlie the contractile function of the heart. Although our understanding of the sarcomere has grown tremendously, the focus has been on ventricular sarcomere isoforms due to the critical role of the ventricle in health and disease. However, atrial-specific or -enriched myofilament protein isoforms, as well as isoforms that become expressed in disease, provide insight into ways this complex molecular machine is fine-tuned. Here, we explore how atrial-enriched sarcomere protein composition modulates contractile function to fulfill the physiological requirements of atrial function. We review how atrial dysfunction negatively affects the ventricle and the many cardiovascular diseases that have atrial dysfunction as a comorbidity. We also cover the pathophysiology of mutations in atrial-enriched contractile proteins and how they can cause primary atrial myopathies. Finally, we explore what is known about contractile function in various forms of atrial fibrillation. The differences in atrial function in health and disease underscore the importance of better studying atrial contractility, especially as therapeutics currently in development to modulate cardiac contractility may have different effects on atrial sarcomere function.

Myosin-binding protein H-like regulates myosin-binding protein distribution and function in atrial cardiomyocytes.

Mutations in atrial-enriched genes can cause a primary atrial myopathy that can contribute to overall cardiovascular dysfunction. MYBPHL encodes myosin-binding protein H-like (MyBP-HL), an atrial sarcomere protein that shares domain homology with the carboxy-terminus of cardiac myosin-binding protein-C (cMyBP-C). The function of MyBP-HL and the relationship between MyBP-HL and cMyBP-C is unknown. To decipher the roles of MyBP-HL, we used structured illumination microscopy, immuno-electron microscopy, and mass spectrometry to establish the localization and stoichiometry of MyBP-HL. We found levels of cMyBP-C, a major regulator of myosin function, were half as abundant compared to levels in the ventricle. In genetic mouse models, loss of MyBP-HL doubled cMyBP-C abundance in the atria, and loss of cMyBP-C doubled MyBP-HL abundance in the atria. Structured illumination microscopy showed that both proteins colocalize in the C-zone of the A-band, with MyBP-HL enriched closer to the M-line. Immuno-electron microscopy of mouse atria showed MyBP-HL strongly localized 161 nm from the M-line, consistent with localization to the third 43 nm repeat of myosin heads. Both cMyBP-C and MyBP-HL had less-defined sarcomere localization in the atria compared to ventricle, yet areas with the expected 43 nm repeat distance were observed for both proteins. Isometric force measurements taken from control and Mybphl null single atrial myofibrils revealed that loss of Mybphl accelerated the linear phase of relaxation. These findings support a mechanism where MyBP-HL regulates cMyBP-C abundance to alter the kinetics of sarcomere relaxation in atrial sarcomeres.

Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.

Aims: Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance. Treatment of AFib involves restoration of the atrial electrical rhythm. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs that involves decreased blood flow velocity and reduced atrial contractility. This suggests that defects in contractility occur in AFib and are revealed upon restoration of rhythm. The aim of this project is to define the contractile remodeling that occurs in AFib. Methods and Results: To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. Atrial cardiomyocytes showed reduced force of contraction in skinned single cardiomyocyte calcium-force studies. There were no significant differences in myosin heavy chain isoform expression. Resting tension is decreased in the AFib samples correlating with reduced full-length titin in the sarcomere. We measured degradation of other myofilament proteins including cMyBP-C, actinin, and cTnI, showing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. Skinned cardiomyocytes from AFib atria showed decreased troponin I phosphorylation, consistent with the increased calcium sensitivity that was found within these cardiomyocytes. Conclusions: With these results it can be concluded that AFib causes alterations in contraction that can be explained by both molecular changes occurring in myofilament proteins and overall myofilament protein degradation. These results provide an understanding of the contractile remodeling that occurs in AFib and provides insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.

Adverse health outcomes among people who inject drugs who engaged in recent sex work: findings from a national survey.

OBJECTIVES: This study explores trends in sex work among people who inject drugs (PWID) by gender and the relationship between sex work and adverse health outcomes including overdose, injection-site, and blood-borne virus (BBV) infections. STUDY DESIGN: The Unlinked Anonymous Monitoring Survey of PWID is an annual cross-sectional survey that monitors BBV prevalence and behaviours, including transactional sex, among PWID recruited through specialist services in England, Wales, and Northern Ireland. METHODS: Trends in sex work among PWID (2011-2021) were described. Data were analysed to assess differences between PWID who engaged in sex work in the past year (sex workers [SWs]) and those who did not (non-SWs) by gender (Pearson Chi2 tests) (2018-2021). Associations between sex work in the past year and adverse health outcomes were investigated using logistic regression. RESULTS: Between 2011 and 2021, sex work among PWID remained stable, with 31% of women and 6.3% of men who inject, reporting having ever engaged in sex work, and 14% of women and 2.2% of men engaging in sex work in the past year. Between 2018 and 2021, SWs had greater odds of reporting symptoms of an injection-site infection (adjusted odds ratio (aOR): 1.68 [95% confidence interval {CI}: 1.31-2.16], P < 0.001) and reporting overdose (aOR: 2.21 [CI: 1.74-2.80], P < 0.001) than non-SWs had in the past year. Among men, SWs had 243% greater odds of having HIV than non-SWs (aOR: 3.43 [CI: 1.03-11.33], P = 0.043). CONCLUSIONS: Our findings highlight disproportionate vulnerability and intersection of overlapping risk factors experienced by PWID SWs and a need for tailored interventions which are inclusive and low-threshold.

Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney.

Chronic kidney disease (CKD), characterized by sustained inflammation and progressive fibrosis, is highly prevalent and can eventually progress to end-stage kidney disease. However, current treatments to slow CKD progression are limited. Sphingosine 1-phosphate (S1P), a product of sphingolipid catabolism, is a pleiotropic mediator involved in many cellular functions, and drugs targeting S1P signaling have previously been studied particularly for autoimmune diseases. The primary mechanism of most of these drugs is functional antagonism of S1P receptor-1 (S1P1) expressed on lymphocytes and the resultant immunosuppressive effect. Here, we documented the role of local S1P signaling in perivascular cells in the progression of kidney fibrosis using primary kidney perivascular cells and several conditional mouse models. S1P was predominantly produced by sphingosine kinase 2 in kidney perivascular cells and exported via spinster homolog 2 (Spns2). It bound to S1P1 expressed in perivascular cells to enhance production of proinflammatory cytokines/chemokines upon injury, leading to immune cell infiltration and subsequent fibrosis. A small-molecule Spns2 inhibitor blocked S1P transport, resulting in suppression of inflammatory signaling in human and mouse kidney perivascular cells in vitro and amelioration of kidney fibrosis in mice. Our study provides insight into the regulation of inflammation and fibrosis by S1P and demonstrates the potential of Spns2 inhibition as a treatment for CKD and potentially other inflammatory and fibrotic diseases that avoids the adverse events associated with systemic modulation of S1P receptors.

Preliminary indications of the burden of COVID-19 among people who inject drugs in England and Northern Ireland and the impact on access to health and harm reduction services.

OBJECTIVE: The aim of the study was to describe the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on people who inject drugs (PWID) in England, Wales and Northern Ireland. STUDY DESIGN: This is a cross-sectional Unlinked Anonymous Monitoring (UAM) Survey of PWID. METHODS: People who had ever injected psychoactive drugs were recruited to the UAM Survey by specialist drug/alcohol services in England, Wales and Northern Ireland. From June 2020, in addition to providing a dried blood spot sample and completing the UAM behavioural questionnaire, participants were asked to complete an enhanced coronavirus disease 2019 (COVID-19) questionnaire. Preliminary data are presented to the end of October and were compared with data from the 2019 UAM Survey, where possible. RESULTS: Between June and October, 288 PWID were recruited from England and Northern Ireland. One in nine (11%; 29/260) PWID reported testing positive for SARS-CoV-2 or experiencing COVID-19 symptoms. Fifteen percent (26/169) reported injecting more frequently in 2020 than in 2019; cocaine injection in the preceding four weeks increased from 17% (242/1456) to 25% (33/130). One in five PWID (19%; 35/188) reported difficulties in accessing HIV and hepatitis testing, and one in four (26%; 47/179) reported difficulties in accessing equipment for safer injecting. CONCLUSIONS: Our preliminary findings suggest that PWID have experienced negative impacts on health, behaviours and access to essential harm reduction, testing and treatment services owing to the COVID-19 pandemic. Continued monitoring through surveillance and research is needed to understand the subsequent impact of COVID-19 on blood-borne virus transmission in this population and on health inequalities.

High prevalence of albuminuria amongst people who inject drugs: A cross-sectional study.

Albuminuria is a key biomarker for cardiovascular disease and chronic kidney disease. Our study aimed to describe the prevalence of albuminuria amongst people who inject drugs in London and to test any potential associations with demographic characteristics, past diagnoses, and drug preparation and administration practices. We carried out a cross-sectional survey amongst people who use drugs in London. The main outcome measure was any albuminuria including both microalbuminuria and macroalbuminuria. Three-hundred and sixteen samples were tested by local laboratory services. Our study initially employed point-of-care testing methods but this resulted in a high number of false positives. Our findings suggest the prevalence of albuminuria amongst PWID is twice that of the general population at 19% (95%CI 15.3-24.0%). Risk factors associated with albuminuria were HIV (aOR 4.11 [95% CI 1.37-12.38]); followed by overuse of acidifier for dissolving brown heroin prior to injection (aOR 2.10 [95% CI 1.04-4.22]). Albuminuria is high amongst people who inject drugs compared to the general population suggesting the presence of increased cardiovascular and renal pathologies. This is the first study to demonstrate an association with acidifier overuse. Dehydration may be common amongst this population and may affect the diagnostic accuracy of point-of-care testing for albuminuria.

Are there missed opportunities for vaccinating against hepatitis B among people who inject drugs in the UK?

Sustaining the impact of hepatitis B virus (HBV) vaccination on incidence and prevalence of HBV infection requires increasing and maintaining the uptake of vaccine among those at risk. In recent years, the level of vaccine uptake among people who inject drugs (PWID) in the UK has levelled-off. Data (2015-2016) from the national unlinked-anonymous monitoring survey of PWID, an annual survey that collects data from PWID across England, Wales and Northern Ireland, were used to examine HBV vaccine uptake. Data from participants who had injected drugs during the previous year were used to investigate sources of hepatitis B vaccine doses as well as factors associated with vaccine uptake. Among the 3175 anti-HBc-negative participants, 3138 (99%) reported their vaccination status; 23% (714) reported no vaccine uptake. Among those not vaccinated, 447 (63%) reported being sexually active and 116 (16%) reported sharing needles and syringes. Majority of those not vaccinated reported accessing services in the previous year that could have provided hepatitis B vaccine doses. These missed opportunities for vaccinating of PWID indicate a need for additional targeted interventions.

'Care and Prevent': rationale for investigating skin and soft tissue infections and AA amyloidosis among people who inject drugs in London.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID. METHODS: Care and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1-P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study. RESULTS: We are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening recommendations and intervention implementation. We aim to recruit 400 PWID from drug treatment services in London, UK. CONCLUSIONS: Care and Prevent is the first study to assess screening feasibility and the prevalence of positive proteinuria, as a marker for AA amyloidosis, among PWID accessing drug treatment services. AA amyloidosis is a serious, yet under-recognised condition for which early intervention is available but not employed.

Low levels of hepatitis C diagnosis and testing uptake among people who inject image and performance enhancing drugs in England and Wales, 2012-15.

INTRODUCTION: People injecting image and performance enhancing drugs (IPEDs) have traditionally not been perceived as being at high risk of hepatitis C virus (HCV) infection. However, recent studies indicate the HCV antibody (anti-HCV) prevalence in this group is 10-times that in the general population. HCV testing uptake and undiagnosed infections are examined using data from a voluntary unlinked-anonymous survey. METHOD: People injecting IPEDs across England and Wales completed a short bio-behavioural survey (2012-15). Anti-HCV status and self-reports of HCV testing were used in the analysis. RESULTS: The participants median age was 31 years, 98% were men, 14% had also injected psychoactive drugs and the anti-HCV prevalence was 4.8% (N=564). Among those who had never injected psychoactive drugs the anti-HCV prevalence was 1.4%; among those who had recently injected psychoactive drugs (preceding 12 months) prevalence was 39% and among those who had done this previously 14% (p<0.001). Overall, 37% had been tested for HCV: among those who had recently injected psychoactive drugs 78% had been tested, as had 56% of those who had injected psychoactive drugs previously; 33% of those never injecting psychoactive drugs were tested (p<0.001). Overall, 44% of those with anti-HCV were aware of this; however, only 14% of those who had never injected psychoactive drugs were aware. CONCLUSIONS: One-in-twenty people who inject IPEDs have anti-HCV. HCV infections among those who had never injected psychoactive drugs were mostly undiagnosed, though this group had a lower prevalence. Targeted HCV testing interventions are also needed for those injecting IPEDs.

Not in the vein: 'missed hits', subcutaneous and intramuscular injections and associated harms among people who inject psychoactive drugs in Bristol, United Kingdom.

BACKGROUND: The extent of intentional or accidental subcutaneous and intramuscular injections and the factors associated with these have rarely been studied among people who inject drugs, yet these may play an important role in the acquisition bacterial infections. This study describes the extent of these, and in particular the factors and harms associated with accidental subcutaneous and intramuscular injections (i.e. 'missed hits'). METHODS: People who inject drugs were recruited using respondent driven sampling. Weighted data was examined using bivariate analyses and logistic regression. RESULTS: The participants mean age was 33 years (31% aged under 30-years), 28% were women, and the mean time since first injection was 12 years (N=329). During the preceding three months, 97% had injected heroin, 71% crack-cocaine, and 16% amphetamines; 36% injected daily. Overall, 99% (325) reported that they aimed to inject intravenously; only three aimed to inject subcutaneously and one intramuscularly. Of those that aimed to inject intravenously, 56% (181) reported ever missing a vein (for 51 this occurred more than four times month on average). Factors associated with 'missed hits' suggested that these were the consequence of poor vascular access, injection technique and/or hygiene. 'Missed hits' were twice as common among those reporting sores/open wounds, abscesses, or redness, swelling and tenderness at injection sites. CONCLUSION: Intentional subcutaneous and intramuscular injections are rare in this sample. 'Missed hits' are common and appear to be associated with poor injection practice. Interventions are required to reduce risk through improving injecting practice and hygiene.

Going into the groin: Injection into the femoral vein among people who inject drugs in three urban areas of England.

BACKGROUND: There have been increasing concerns about injection into the femoral vein - groin injecting - among people who inject drugs in a number of countries, though most studies have been small. The extent, reasons and harms associated with groin injecting are examined. METHOD: Participants were recruited using respondent driven sampling (2006-2009). Weighted data was examined using bivariate analyses and logistic regression. RESULTS: The mean age was 32 years; 25% were women (N=855). During the preceding 28 days, 94% had injected heroin and 13% shared needles/syringes. Overall, 53% reported ever groin injecting, with 9.8% first doing so at the same age as starting to inject. Common reasons given for groin injecting included: "Can't get a vein elsewhere" (68%); "It is discreet" (18%); and "It is quicker" (14%). During the preceding 28 days, 41% had groin injected, for 77% this was the only body area used (for these "It is discreet" was more frequently given as a reason). In the multivariable analysis, groin injection was associated with: swabbing injection sites; saving filters for reuse; and receiving opiate substitution therapy. It was less common among those injecting into two body areas, and when other people (rather than services) were the main source of needles. Groin injection was more common among those with hepatitis C and reporting ever having deep vein thrombosis or septicaemia. CONCLUSIONS: Groin injection was common, often due to poor vascular access, but for some it was out of choice. Interventions are required to reduce injecting risk and this practice.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.

Factors associated with recently acquired hepatitis C virus infection in people who inject drugs in England, Wales and Northern Ireland: new findings from an unlinked anonymous monitoring survey.

Monitoring infections and risk in people who inject drugs (PWID) is important for informing public health responses. In 2011, a novel hepatitis C antibody (anti-HCV) avidity-testing algorithm to identify samples compatible with recent primary infection was introduced into a national surveillance survey. PWID are recruited annually, through >60 needle-and-syringe programmes and prescribing services. Of the 980 individuals that could have been at risk of HCV infection, there were 20 (2%) samples that were compatible with recent primary infection. These were more common among: those imprisoned ⩾5 times [8/213; adjusted odds ratio (aOR) 8·7, 95% confidence interval (CI) 2·04-37·03]; women (8/230; aOR 3·8, 95% CI 1·41-10·38); and those ever-infected with hepatitis B (5/56; aOR 6·25, 95% CI 2·12-18·43). This study is the first to apply this algorithm and to examine the risk factors associated with recently acquired HCV infection in a national sample of PWID in the UK. These findings highlight underlying risks and suggest targeted interventions are needed.

Injection site infections and injuries in men who inject image- and performance-enhancing drugs: prevalence, risks factors, and healthcare seeking.

People who inject drugs are vulnerable to infections and injuries at injection sites, but these have rarely been studied in those injecting image- and performance-enhancing drugs (IPEDs). This study examined the factors associated with reported symptoms of injection site infections and injuries in IPED injectors. Of the 366 male IPED injectors surveyed, 42% reported ever having redness, swelling and tenderness (36% in the preceding year), and 6·8% had ever had an abscess or open wound at an injection site. Having these symptoms was associated with a range of factors related to drug use and healthcare utilization. One sixth (17%) of those reporting redness, tenderness and swelling had ever sought treatment, as had the majority (76%) of those reporting an abscess, sore or open wound. Most common sources of advice were emergency clinics and General Practitioners. Interventions are needed to support access to appropriate injecting equipment and provide targeted harm reduction advice.

Healthcare seeking and hospital admissions by people who inject drugs in response to symptoms of injection site infections or injuries in three urban areas of England.

People who inject drugs (PWID) are vulnerable to infections and injuries at injection sites. The factors associated with reporting symptoms of these, seeking related advice, and hospital admission are examined. PWID were recruited in Birmingham, Bristol and Leeds using respondent-driven sampling (N = 855). During the preceding year, 48% reported having redness, swelling and tenderness (RST), 19% an abscess, and 10% an open wound at an injection site. Overall, 54% reported ⩾1 symptoms, with 45% of these seeking medical advice (main sources emergency departments and General Practitioners). Advice was often sought ⩾5 days after the symptom first appeared (44% of those seeking advice about an abscess, 45% about an open wound, and 35% for RST); the majority received antibiotics. Overall, 9·5% reported hospital admission during the preceding year. Ever being diagnosed with septicaemia and endocarditis were reported by 8·8% and 2·9%, respectively. Interventions are needed to reduce morbidity, healthcare burden and delays in accessing treatment.