Examining the effectiveness of the Gateway conditional caution on health and well-being of young adults committing low-level offences: a randomised controlled trial.

BACKGROUND: Young adults who commit low-level offences commonly have a range of health and social needs and are significantly over-represented in the criminal justice system. These young adults may need to attend court and potentially receive penalties including imprisonment. Alternative routes exist, which can help address the underlying causes of offending. Some feel more should be done to help young adults entering the criminal justice system. The Gateway programme was a type of out-of-court disposal developed by Hampshire Constabulary, which aimed to address the complex needs of young adults who commit low-level crimes. This study aimed to evaluate the effectiveness and cost-effectiveness of the Gateway programme, issued as a conditional caution, compared with usual process. METHODS: The Gateway study was a pragmatic, parallel-group, superiority randomised controlled trial that recruited young adults who had committed a low-level offence from four sites covering Hampshire and Isle of Wight. The primary outcome was mental health and well-being measured using the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes were quality of life, alcohol and drug use, and recidivism. Outcomes were measured at 4, 16 and 52 weeks postrandomisation. RESULTS: Due to issues with retention of participants and low data collection rates, recruitment ended early, with 191 eligible participants randomised (Gateway 109; usual process 82). The primary outcome was obtained for 93 (48.7%) participants at 4 weeks, 93 (48.7%) at 16 weeks and 43 (22.5%) at 1 year. The high attrition rates meant that effectiveness could not be assessed as planned. CONCLUSIONS: Gateway is the first trial in a UK police setting to have a health-related primary outcome requiring individual data collection, rather than focusing solely on recidivism. We demonstrated that it is possible to recruit and randomise from the study population, however follow-up rates were low. Further work is needed to identify ways to facilitate engagement between researchers and vulnerable populations to collect data. TRIAL REGISTRATION NUMBER: ISRCTN11888938.

Lessons from the Gateway programme, aimed at improving health and life chances for young people committing low-level offences: a qualitative evaluation.

BACKGROUND: Young people who commit criminal offences are often affected by mental health issues, including drug and alcohol misuse, with many leading chaotic lifestyles. Gateway was a pioneering court-diversion programme aimed to reduce reoffending and improve the health and wellbeing of people aged 18-24 years who had been questioned for a low-level offence. The Gateway Study consisted of a pragmatic, parallel-group, superiority randomised controlled trial (RCT) of the programme's effectiveness, and its qualitative evaluation. We aimed to determine barriers and enablers for implementation of Gateway and recruitment into the RCT. METHODS: We evaluated the implementation of Gateway, a 16-week conditional caution designed by Hampshire Constabulary and delivered predominantly by third sector organisations. Following a needs assessment, young people received individual support from a Gateway navigator and attended self-development workshops. Recruitment into the RCT took place across four sites across Hampshire and Isle of Wight, UK. Semi-structured interviews were carried out with Gateway stakeholders over three time periods in 2018-22, with additional timepoints in the first time period. Purposive samples of Gateway clients and recruiters, as well as all of Gateway staff, were interviewed. Thematic analysis was applied, with an inductive and predominantly reflexive approach, for each group of participants in each time period. FINDINGS: Between Dec 19, 2018, and May 3, 2022, qualitative interviews were held with 28 Gateway clients, 17 Gateway project staff, and 13 police officers and civilian staff who acted as recruiters into the programme and RCT. Various themes related to engagement were identified, with multiple subthemes and unique insights. The core themes can be classified as follows (with examples of factors influencing engagement): (1) setup for Gateway delivery and RCT recruitment (eg, multi-agency partnerships, physical locations, training); (2) young people's lifestyles and needs (eg, personal circumstances, pre-existing expectations, attitude towards Gateway); (3) priorities and culture in the organisations (eg, workload priorities, job satisfaction, inter-stakeholder relationships). INTERPRETATION: The Gateway Study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. Engaging vulnerable young people and the police in research comes with its own, specific challenges. The insights shared as a result of this evaluation can inform the design of interventions and studies that target similarly vulnerable people or are based in similar settings. Awareness of the potential barriers and facilitators can help public health researchers and practitioners plan accordingly and prevent or mitigate some of the low-engagement issues. FUNDING: National Institute for Health and Care Research (NIHR).

Determining the Prevalence and Incidence of SARS-CoV-2 Infection in Prisons in England: Protocol for a Repeated Panel Survey and Enhanced Outbreak Study.

BACKGROUND: There are over 80,000 people imprisoned in England and Wales in 117 prisons. The management of the COVID-19 pandemic presents particular challenges in this setting where confined, crowded, and poorly ventilated conditions facilitate the rapid spread of infectious diseases. OBJECTIVE: The COVID-19 in Prison Study aims to examine the epidemiology of SARS-CoV-2 in prisons in England in order to inform public health policy and practice during the pandemic and recovery. The primary objective is to estimate the proportion of positive tests of SARS-CoV-2 infection among residents and staff within selected prisons. The secondary objectives include estimating the incidence rate of SARS-CoV-2 infection and examining how the proportion of positive tests and the incidence rate vary among individual, institutional, and system level factors. METHODS: Phase 1 comprises a repeated panel survey of prison residents and staff in a representative sample of 28 prisons across England. All residents and staff in the study prisons are eligible for inclusion. Participants will be tested for SARS-CoV-2 using a nasopharyngeal swab twice (6 weeks apart). Staff will also be tested for antibodies to SARS-CoV-2. Phase 2 focuses on SARS-CoV-2 infection in prisons with recognized COVID-19 outbreaks. Any prison in England will be eligible to participate if an outbreak is declared. In 3 outbreak prisons, all participating staff and residents will be tested for SARS-CoV-2 antigens at the following 3 timepoints: as soon as possible after the outbreak is declared (day 0), 7 days later (day 7), and at day 28. They will be swabbed twice (a nasal swab for lateral flow device testing and a nasopharyngeal swab for polymerase chain reaction testing). Testing will be done by external contractors. Data will also be collected on individual, prison level, and community factors. Data will be stored and handled at the University of Southampton and Public Health England. Summary statistics will summarize the prison and participant characteristics. For the primary objective, simple proportions of individuals testing positive for SARS-CoV-2 and incidence rates will be calculated. Linear regression will examine the individual, institutional, system, and community factors associated with SARS-CoV-2 infection within prisons. RESULTS: The UK Government's Department for Health and Social Care funds the study. Data collection started on July 20, 2020, and will end on May 31, 2021. As of May 2021, we had enrolled 4192 staff members and 6496 imprisoned people in the study. Data analysis has started, and we expect to publish the initial findings in summer/autumn 2021. The main ethical consideration is the inclusion of prisoners, who are vulnerable participants. CONCLUSIONS: This study will provide unique data to inform the public health management of SARS-CoV-2 in prisons. Its findings will be of relevance to health policy makers and practitioners working in prisons. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30749.

The Enhanced Liver Fibrosis test is associated with liver-related outcomes in postmenopausal women with risk factors for liver disease.

BACKGROUND: Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit life-saving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS). METHODS: In a cohort of 95,126 we performed a case-control study measuring ELF in blinded samples from 173 participants with self-reported high alcohol use and / or BMI ≥25 kg/m2 comprising all 58 cases who developed LRE and 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8.5 years. RESULTS: Using Cox regression at an ELF threshold of 10.51 hazard ratios (HR) for LRE were 4.88 (95% confidence interval (CI) 2.37-10.03) (unadjusted model) and 4.62 (95% CI 2.12-10.08) (adjusted for deprivation and self-reported hypertension, heart disease, hypercholesterolaemia and diabetes). At a threshold of 9.8 HR for LRE were 2.21 (95% CI 1.22-3.97) (unadjusted model) and 2.18 (95% CI 1.19-4.01) (adjusted). ELF was evaluated as a time dependent variable by generating time-dependent Cox models; HRs at an ELF threshold of 10.51 were 1.94 (95% CI 1.10-3.39) (unadjusted) and 2.05 (95% CI 1.16-3.64) (adjusted) and at a threshold of 9.8 HRs were 1.85 (95% CI 1.09-3.15) (unadjusted) and 1.80 (95% CI 1.04-3.13) (adjusted). Area under the receiver operating characteristic curve for recruitment ELF predicting LRE was 0.58 (95% CI 0.49-0.68), and for second subsequent ELF 0.61 (95% CI 0.52-0.71). CONCLUSION: This study demonstrates the association between ELF and CLD in postmenopausal women with risk factors for liver disease, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the potential of ELF as a prognostic tool in health checks in primary care. TRIAL REGISTRATION: This study is nested in UKCTOCS. UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Registered 06/04/2000.

The testing of people with any risk factor for hepatitis C in community pharmacies is cost-effective.

New antiviral drugs with high efficacy mean the hepatitis C virus (HCV) can now be eliminated. To achieve this, it is necessary to identify undiagnosed cases of HCV. However, the costs of testing should be considered when judging the overall cost-effectiveness of treatment. This study describes the cost-effectiveness of a community pharmacy testing service in a population of people at risk of HCV living on the Isle of Wight (United Kingdom). Dry blood spot testing was conducted in anyone with a known risk factor for HCV in 20 community pharmacies. The outcomes and costs were entered into a Markov model. Cost and health utilities from the model were used to calculate an incremental cost-effectiveness ratio (ICER). In 24 months, 186 tests were conducted, 13 were positive for HCV RNA and six of these (46%) received treatment during the follow-up period. All achieved a sustained virological response at 3 months. The overall cost of the testing and treatment intervention was £242 183, and the ICER for the service was £3689 per quality-adjusted life year (QALY) gained. If screening had been restricted to just people with a history of injecting drug use (PWID) the ICER would have been £4865 per QALY gained. The service was effective at identifying people with HCV infection, and despite the additional cost of targeted testing, its cost-effectiveness was below the commonly accepted thresholds. In this setting, restricting targeted testing to PWID would not improve the cost-effectiveness.

Cost-comparison analysis of FIB-4, ELF and fibroscan in community pathways for non-alcoholic fatty liver disease.

BACKGROUND: The identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies. METHODS: A probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected. RESULTS: Introduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively. The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline. CONCLUSION: Our analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.

Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease.

UNLABELLED: Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87. CONCLUSION: PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH.

Predicted effects of treatment for HCV infection vary among European countries.

BACKGROUND & AIMS: The dynamics of hepatitis C virus (HCV) infection, as well as screening practices and access to therapy, vary among European countries. It is important to determine the magnitude of the effects of such differences on incidence and mortality of infection. We compared the dynamics of infection and screening and treatment practices among Belgium, France, Germany, Italy, Spain, and the United Kingdom. We also assessed the effects of treatment with pegylated interferon and additional effects of triple therapy with protease inhibitors. METHODS: We created a country-specific Markov model of HCV progression based on published epidemiologic data (on HCV prevalence, screening, genotype, alcohol consumption among patients, and treatments) and reports of competitive and hepatocellular carcinoma mortality for the 6 countries. The model was used to predict the incidence of HCV-related cirrhosis and its mortality until 2021 for each country. RESULTS: From 2002 to 2011, antiviral therapy reduced the cumulative incidence of cirrhosis by 7.1% and deaths by 3.4% overall. Reductions in incidence and mortality values ranged from 4.0% and 1.9%, respectively, in Italy to 16.3% and 9.0%, respectively, in France. From 2012 to 2021, antiviral treatment of patients with HCV genotype 1 infection that includes protease inhibitor-based triple therapy will reduce the cumulative incidence of cirrhosis by 17.7% and mortality by 9.7% overall. The smallest reduction is predicted for Italy (incidence reduced by 10.1% and mortality by 5.4%) and the highest is for France (reductions of 34.3% and 20.7%, respectively). CONCLUSIONS: Although HCV infection is treated with the same therapies in different countries, the effects of the therapies on morbidity and mortality vary significantly. In addition to common guidelines that are based on virologic response-guided therapy, there is a need for public health policies based on population-guided therapy.

Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis.

BACKGROUND: FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminal propeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1). While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers. METHODS: In the present study, the ELF-test was analyzed retrospectively in patients with chronic liver disease, who received a liver biopsy, transient elastography (TE) and the FibroTest using histology as the reference method. Histology was classified according to METAVIR and the Ludwig's classification (F0-F4) for patients with chronic hepatitis C and B virus (HCV, HBV) infection and primary biliary cirrhosis (PBC), respectively. RESULTS: Seventy-four patients were analysed: 36 with HCV, 10 with HBV, and 28 with PBC. The accuracy (AUROC) for the diagnosis of significant fibrosis (F≥2) for ELF and FibroTest was 0.78 (95%CI:0.67-0.89) and 0.69 (95%-CI:0.57-0.82), respectively (difference not statistically significant, n.s.). The AUROC for the diagnosis of liver cirrhosis was 0.92 (95%CI:0.83-1,00), and 0.91 (95%CI:0.83-0.99), respectively (n.s.). For 66 patients with reliable TE measurements the AUROC for the diagnosis of significant fibrosis (cirrhosis) for TE, ELF and FT were 0.80 (0.94), 0.76 (0.92), and 0.67 (0.91), respectively (n.s.). CONCLUSION: FibroTest and ELF can be performed with comparable diagnostic accuracy for the non-invasive staging of liver fibrosis. Serum tests are informative in a higher proportion of patients than transient elastography.

Variation in hepatitis C services may lead to inequity of heath-care provision: a survey of the organisation and delivery of services in the United Kingdom.

BACKGROUND: Chronic hepatitis C infection (CHC) is a major healthcare problem. Effective anti-viral therapy is available. To maximise population effectiveness, co-ordinated services for detection and management of patients with CHC are required. There is a need to determine patterns of healthcare delivery to plan improvements. A study was conducted to determine workload, configuration and care processes of current UK services available to manage patients with CHC. METHODS: A cross-sectional questionnaire survey of consultant members of British Association for the Study of the Liver (n = 53), Infectious Disease consultants (n = 43), and a 1 in 5 sample of Genito-Urinary Medicine (n = 48) and gastroenterologists (n = 200). RESULTS: Response rate was 70%. 40% of respondents provided a comprehensive service (included treatment and follow-up): speciality of clinical leads identified as Hepatology (37%); Gastroenterology (47%); and Infectious Disease (16%). The estimated number of patients managed by respondents was about 23,000 with an upward trend over the previous 3 years. There was variation between comprehensive service providers, including unit size, eligibility criteria for treatment, and drug regimes. Key barriers to quality of care identified were staffing capacity, funding of treatment and patient non-attendance. Most English strategic health authorities had at least one comprehensive service provider. CONCLUSION: There was significant variation in all aspects of the patient pathway which may contribute to inequity of health care provision. Services need to be expanded to form geographical clinical networks, and properly resourced to ensure greater uptake and more equitable delivery of services if the future burden of chronic liver disease is to be reduced.