Impact of Hepatitis C Treatment as Prevention for People Who Inject Drugs is sensitive to contact network structure

Treatment as Prevention (TasP) using directly-acting antivirals has been advocated for Hepatitis C Virus (HCV) in people who inject drugs (PWID), but treatment is expensive and TasP’s effectiveness is uncertain. Previous modelling has assumed a homogeneously-mixed population or a static network lacking turnover in the population and injecting partnerships. We developed a transmission-dynamic model on a dynamic network of injecting partnerships using data from survey of injecting behaviour carried out in London, UK. We studied transmission on a novel exponential-clustered network, as well as on two simpler networks for comparison, an exponential unclustered and a random network, and found that TasP’s effectiveness differs markedly. With respect to an exponential-clustered network, the random network (and homogeneously-mixed population) overestimate TasP’s effectiveness, whereas the exponential-unclustered network underestimates it. For all network types TasP’s effectiveness depends on whether treated patients change risk behaviour, and on treatment coverage: higher coverage requires fewer total treatments for the same health gain. Whilst TasP can greatly reduce HCV prevalence, incidence of infection, and incidence of reinfection in PWID, assessment of TasP’s effectiveness needs to take account of the injecting-partnership network structure and post-treatment behaviour change, and further empirical study is required

Practising critical resilience as an advanced peer support worker in London: A qualitative evaluation of a peer-led hepatitis C intervention amongst people experiencing homelessness who inject drugs

Background: Peer support has been used as a mechanism to facilitate active engagement with healthcare amongst underserved populations. The HepCare project upskilled experienced peer support workers (PSWs) to become equal members of a service provider team, taking on advanced clinical roles normally carried out by medical or nursing specialists. Method: A participatory case study approach was taken to the study following the methodological guidance of Merriam (1998). The subject of the case in our study is the advanced peer support workers (APSWs) functioning in the HepCare project as service providers. The object of the case is an exploration of their transition to service provider in the HCV screening and treatment support service. Five peer led in-depth interviews with APSWs were supplemented by a survey of health professionals, interviews with service users, documentary evidence in the form of job descriptions, observational notes and a blog from the field. Thematic analysis of the data was conducted, refined and finalised in a workshop with the research team and APSW participants. Results Three themes were generated from the data that explore the peer support worker's transition to APSW in the programme: Transition to Integration, Retaining ‘Peerness’, and Practising Critical Resilience. The advocacy and support enacted by the APSWs through the HepCare project, offer purpose and meaning alongside integration into a new social group. This is buffered by the supportive context of the programme and facilitates a motivating sense of worth. Conclusion: The programme offers policy guidance for the structured career development of APSWs and a platform for enactment of critical resilience as they transition to their advanced role, in the healthcare provider team

Integrated Hepatitis C Care for People Who Inject Drugs (Heplink): Protocol for a Feasibility Study in Primary Care (Preprint)

Background: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and death. Drug use remains the significant cause of new infections in the European Union, with estimates of HCV antibody prevalence among people who inject drugs ranging from 5% to 90% in 29 European countries. In Ireland and the European Union, primary care is a key area to focus efforts to enhance HCV diagnosis and treatment among people who inject drugs. Objective: The Heplink study aims to improve HCV care outcomes among opiate substitution therapy (OST) patients in general practice by developing an integrated model of HCV care and evaluating its feasibility, acceptability, and likely efficacy. Methods: The integrated model of care comprises education of community practitioners, outreach of an HCV-trained nurse into general practitioner (GP) practices, and enhanced access of patients to community-based evaluation of their HCV disease (including a novel approach to diagnosis, that is, Echosens FibroScan Mini 430). A total of 24 OST-prescribing GP practices were recruited from the professional networks and databases of members of the research consortium. Patients were eligible if they are aged ≥18 years, on OST, and attend the practice for any reason during the recruitment period. Baseline data on HCV care processes and outcomes were extracted from the clinical records of participating patients. Results: This study is ongoing and has the potential to make an important impact on patient care and provide high-quality evidence to help GPs make important decisions on HCV testing and onward referral. Conclusions: A substantial proportion of HCV-positive patients on OST in general practice are not engaged with specialist hospital services but qualify for direct-acting antiviral drugs treatment. The Heplink model has the potential to reduce HCV-related morbidity and mortality. Registered Report Identifier: RR1-10.2196/904

Hepatitis B vaccination uptake in hard-to-reach populations in London: a cross-sectional study

BACKGROUND: In the UK, hepatitis B virus (HBV) incidence is associated with migrants from particular high-burden countries and population groups deemed 'hard-to-reach' by standard healthcare services: the homeless, people who inject drugs and ex-prisoners. Currently, there is a national targeted HBV vaccine policy for such at-risk groups, but there is limited recent evidence about 1) the levels of vaccine uptake, 2) the factors associated with incomplete vaccination, and 3) reasons for incomplete vaccination. METHODS: A questionnaire capturing social and medical history, demographic factors and information about HBV vaccination status was completed by individuals deemed hard-to-reach due to socio-structural factors that criminalise, isolate and stigmatise who consented to participate in a randomised controlled trial of a peer intervention to promote engagement with hepatitis C services. The questionnaire also captured the reasons for incomplete vaccination. Descriptive, univariable and multivariable regression analyses were undertaken. RESULTS: Three hundred fourty six participants completed the questionnaire. 1) 52.3% (n = 181) reported full HBV vaccination. 2) Within a multivariable model adjusting for sociodemographic variables, the presence of one or two or more socio-structural factors that are included in the national targeted vaccination policy was associated with protection against incomplete HBV vaccination (51.7% vaccine coverage in those with one factor, odds ratio 0.43 [95% confidence interval 0.20-0.92]); 70.1% coverage with two or more factors, 0.19 [0.09-0.39]; overall p-value < 0.001). Being female was also associated with lower vaccine uptake (2.37 [1.24-4.57], 0.01). Examining the socio-structural factors individually, intravenous drug use was associated with protection against incomplete HBV vaccination. 3) The most common reasons declared for incomplete vaccination were never being offered the vaccine or not returning for further doses. CONCLUSION: Within this study of HBV vaccination uptake among hard-to-reach population groups in London, UK, we document 52.3% coverage of the full vaccine course. Critically, although participants recommended for immunisation within national guidelines had an increased likelihood of receiving a complete vaccine course, we note surprisingly low coverage in the presence of the risk factors that are national indicators for vaccination. Public health bodies should make additional efforts to improve coverage in the hard-to-reach through improved vaccine delivery systems. TRIAL REGISTRATION: ISRCTN24707359 , Registered 19th October 2012

Humusqualität und Bodenstruktur: Was kontrolliert die Lachgas-Emissionen aus landwirtschaftlich genutzten Böden?

In den letzten Jahrzehnten wurde der globale N-Kreislauf nicht nur durch die Verbrennung fossiler Energieträger, sondern auch durch Anwendung von Düngemitteln drastisch verändert. Gefährdung des Grundwassers und Beitrag zur globalen Klimaentwicklung sind bekannte Folgewirkungen. In Böden ist die Denitrifikation hauptverantwortlich für die Rückführung des Stickstoffs in die Atmosphäre und gehört somit zu den Schlüsselprozessen im N-Kreislauf. Obwohl längst bekannt ist, dass denitrifizierende Bodenorganismen hierfür organische Bodensubstanz (OBS) sowohl als C-Substrat als auch als Elektronendonator nutzen, ist hierbei die Rolle funktioneller OBS-Fraktionen (Humusqualität) sowie deren räumliche und zeitliche Verfügbarkeit in unterschiedlichen Aggregatgrößenfraktionen weitestgehend unbekannt. Aus diesem Grund werden die Auswirkungen spezifischer funktioneller OBS-Fraktionen (gelöste und partikuläre OBS) auf den Beginn und das Ausmaß der Denitrifikation in definierten Inkubationsexperimenten untersucht. Insbesondere für die N2O-Bildung durch Denitrifikation scheinen anoxische „Mikrohabitate“ im Inneren der Aggregate relevant. Im Statischen Düngeversuch in Bad Lauchstädt untersuchen wir daher den Einfluss langfristiger Düngeranwendungen (Applikation von N-, NP- und organischem Dünger) auf die Akkumulation bestimmter funktioneller OBS-Fraktionen sowie auf die Aggregatstruktur und infolgedessen auf das Treibhausgasemissionspotential (neben N2O auch CO2 und CH4). Gasemissionsmessungen aus ungestörten Bodenproben sollen zeigen, inwieweit das Düngungsmanagement über die Kontrolle der Humusqualität und/oder des Aggregationsstatus die Treibhausgasemissionen aus landwirtschaftlich genutzten Böden steuert

Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study.

INTRODUCTION: An improved understanding of factors explaining tuberculosis (TB) treatment response is urgently needed to help clinicians optimise and personalise treatment and assist scientists undertaking novel treatment regimen trials. Promising outcome proxy measures, including sputum bacillary load and host immune response, are widely reported with variable results. However, they have not been studied together in combination with antibiotic exposure. The aim of this observational cohort study is to investigate which antibiotic exposures correlate with sputum bacillary load and which with the host immune response. Subsequently, we will explore if these correlations can be used to inform a candidate combined biomarker predicting cure. METHODS AND ANALYSIS: All patients aged ≥ 18, diagnosed with drug-sensitive pulmonary TB (culture or molecular test), eligible for standard anti-TB treatment, at selected London, UK TB Services, will be invited to participate in this observational cohort study (target sample size=210). Patients will be asked to give blood for host transcriptomics and antibiotic plasma exposure, in addition to standard of care sputum samples for bacillary load. Antibiotic plasma concentrations will be quantified using a validated liquid chromatograph triple quadrupole mass spectrometer (LC-MS/MS) assay and sputum bacillary load by mycobacterial growth incubator tube time to positivity. Expression from a total of 35 prespecified host blood genes will be quantified using NanoString®. Antibiotic exposure, sputum bacillary load and host blood transcriptomic time series data will be analysed using nonlinear mixed-effects models. Correlations between combinations of longitudinal biomarkers and microbiological cure at the end of treatment and remaining relapse free for 1 year thereafter will be analysed using logistic regression and Cox proportional hazard models. ETHICS AND DISSEMINATION: The observational cohort study has been approved by the UK's HRA REC (20/SW/0007). Written informed consent will be obtained. Results will be disseminated via publication, presentation and through engagement with institutes/companies developing novel anti-TB treatment combinations

Improving engagement with healthcare in hepatitis C: a randomised controlled trial of a peer support intervention

National Institute for Health Research Policy Research Programme (‘Effectiveness of testing for treatment of hard-to-reach groups for latent tuberculosis, hepatitis B virus and hepatitis C virus in England: The HALT Study’, 015/0306

HEPCARE EUROPE- A Case study of a Service Innovation Project Aiming at Improving the Elimination of HCV in Vulnerable Populations in Four European Cities

OBJECTIVES: Hepatitis C Virus (HCV) is an important cause of chronic liver disease. Among at-risk populations, access to diagnosis and treatment is challenging. We describe an integrated model of care, Hepcare Europe, developed to address this challenge. METHODS: Using a case-study approach, we describe the cascade of care outcomes at all sites. Costing analyses estimated the cost per person screened and linked to care. RESULTS: A total of 2608 participants were recruited across 218 clinical sites. HCV antibody test results were obtained for 2568(98.5%), 1074(41.8%) were antibody-positive, 687(60.5%) tested positive for HCV-RNA, 650(60.5%) were linked to care and 319(43.5%) started treatment. 196(61.4%) of treatment initiates achieved a Sustained Viral Response (SVR) at dataset closure, 108(33.9%) were still on treatment, 8(2.7%) defaulted from treatment, and 7(2.6%) had a virologic failure or died. The cost per person screened varied from Є194 to Є635, while cost per person linked to care varied from Є364 to Є2035. CONCLUSIONS: Hepcare enhanced access to HCV treatment and cure, costs were affordable in all settings, offering a framework for scale-up and reproducibility

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 )

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study.

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 )