Increased risk of non-fatal overdose associated with non-prescribed benzodiazepine use in Scotland, UK.

BACKGROUND: Drug-related deaths (DRDs) in Scotland increased for seven years in a row between 2014 and 2020, consolidating Scotland's place at the top of the United Kingdom and European drug-related mortality charts. One of the defining features of this recent and rapid rise has been the role of benzodiazepines, which are now involved in the majority of all DRDs. These deaths are linked to use of non-prescribed, benzodiazepine-type novel psychoactive substances (NPS) which have been identified by the United Nations as a global threat to public health. This study aimed to estimate the prevalence and determinants of non-prescribed benzodiazepine use and its association with recent non-fatal overdose among a national sample of people who inject drugs (PWID). METHODS: Data from the 2019-20 Needle Exchange Surveillance Initiative (NESI) was analysed using logistic regression. NESI is a voluntary, anonymous, biennial, cross-sectional, bio-behavioural survey of PWID attending community-based services providing injecting equipment in mainland Scotland. RESULTS: Prevalence of non-prescribed benzodiazepine use in the past six months was 52% and significantly associated with age (aOR 0.97, 0.96-0.98), frequent incarceration (aOR 1.29, 1.07-1.57), recent public injecting (aOR 3.25, 2.33-4.55), a recent methadone prescription (aOR 1.87, 1.51-2.33), and a history of benzodiazepine prescription (aOR 1.92, 1.47-2.52). In addition, non-prescribed benzodiazepine use was significantly associated with non-fatal overdose in the past year among PWID (aOR 2.47, 1.90-3.21). CONCLUSION: This study found a high prevalence of non-prescribed benzodiazepine use among a national sample of PWID in Scotland. Prevalence was highest among populations known to be at increased risk of drug-related death and use was strongly associated with overdose. These novel findings highlight the scale of the non-prescribed benzodiazepine issue Scotland faces, and the urgency required to expand its harm reduction infrastructure to address this unique element of its overdose crisis.

MR elastography-based staging of liver fibrosis in Fontan procedure associated liver disease is confounded by effects of venous congestion.

AIM: To compare targeted and global liver stiffness measured by magnetic resonance elastography (MRE) with liver biopsy in patients who have undergone the Fontan procedure, and to assess the relationship between liver stiffness and fibrosis stage. MATERIALS AND METHODS: Targeted and global liver stiffness was compared with a quantification of liver fibrosis measured by percentage of Sirius Red (%SR) staining of biopsy samples. MRE values were compared with three other biopsy-scoring methods: Ishak, Scheuer/Ludwig-Batts/Metavir, and congestive hepatic fibrosis score (CHFS). Additionally, in patients who had two or more MRE studies, global liver stiffness was compared for longitudinal assessment. RESULTS: Thirty-four patients were included in the study, with a mean age of 16.2 years. There was no statistically significant correlation between MRE-derived liver stiffness and Ishak score, Metavir score, %SR staining, and CHFS score. Twenty patients had multiple MRE studies, with a mean age of 16.5 years, and these showed a statistically significant increase in mean liver stiffness from 3.72 to 4.68 (26% increase) within an average period of 24 months. CONCLUSIONS: The lack of correlation of liver stiffness with fibrosis stage observed in this study indicates that the effects of venous congestion in Fontan patients can confound the use of liver stiffness as a biomarker for fibrosis as assessed by percentage of SR staining, Ishak score, Metavir score, and CHFS score. These results provide motivation for further development of magnetic resonance imaging-based biomarkers to increase the specificity in the assessment of Fontan-associated liver disease. A steady increase in liver stiffness observed in these patients may be useful for longitudinal follow-up of liver health.

Liver function tests in primary care provide a key opportunity to diagnose and engage patients with hepatitis C.

Since the advent of direct-acting antiviral therapy, the elimination of hepatitis c virus (HCV) as a public health concern is now possible. However, identification of those who remain undiagnosed, and re-engagement of those who are diagnosed but remain untreated, will be essential to achieve this. We examined the extent of HCV infection among individuals undergoing liver function tests (LFT) in primary care. Residual biochemistry samples for 6007 patients, who had venous blood collected in primary care for LFT between July 2016 and January 2017, were tested for HCV antibody. Through data linkage to national and sentinel HCV surveillance databases, we also examined the extent of diagnosed infection, attendance at specialist service and HCV treatment for those found to be HCV positive. Overall HCV antibody prevalence was 4.0% and highest for males (5.0%), those aged 37-50 years (6.2%), and with an ALT result of 70 or greater (7.1%). Of those testing positive, 68.9% had been diagnosed with HCV in the past, 84.9% before the study period. Most (92.5%) of those diagnosed with chronic infection had attended specialist liver services and while 67.7% had ever been treated only 38% had successfully cleared infection. More than half of HCV-positive people required assessment, and potentially treatment, for their HCV infection but were not engaged with services during the study period. LFT in primary care are a key opportunity to diagnose, re-diagnose and re-engage patients with HCV infection and highlight the importance of GPs in efforts to eliminate HCV as a public health concern.

Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.

BACKGROUND: Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection. METHODS: We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses. RESULTS: We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans. CONCLUSIONS: Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.

National population prevalence of antibodies to SARS-CoV-2 among pregnant women in Scotland during the second wave of the COVID-19 pandemic: a prospective national serosurvey.

OBJECTIVES: This study aimed to determine SARS-CoV-2 seroprevalence among pregnant women in the Scottish population during the second wave of the COVID-19 pandemic. STUDY DESIGN: Prospective national serosurvey. METHODS: We tested 13,428 residual samples retrieved from pregnant women participating in the first trimester combined ultrasound and biochemical screening for fetal trisomy across Scotland for SARS-CoV-2 antibodies over a 6-month period from November 2020 to April 2021. Seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. RESULTS: Seroprevalence rates in the antenatal samples significantly increased from 5.5% (95% confidence interval [CI] 4.7%-6.5%) in the 5-week period up to and including International Organization for Standardization (ISO) Week 51 (w/b Monday 14 December 2020) to 11.3% (95% CI 10.1%-12.6%) in the 5-week period up to and including ISO Week 14 (w/b Monday 5 April 2021). Increasing seroprevalence trends across the second wave were observed among all age groups. CONCLUSIONS: By the end of the second wave of the COVID-19 pandemic, approximately one in 10 women tested around the end of the first trimester of pregnancy had antibodies to SARS-CoV-2, suggesting that the vast majority were still susceptible to COVID-19 as they progressed to the later stages of pregnancy, when risks from infection are elevated for both mother and baby.

National population prevalence of antibodies to SARS-CoV-2 in Scotland during the first and second waves of the COVID-19 pandemic.

OBJECTIVES: Studies that measure the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('seroprevalence') are essential to understand population exposure to SARS-CoV-2 among symptomatic and asymptomatic individuals. We aimed to measure seroprevalence in the Scottish population over the course of the COVID-19 pandemic - from before the first recorded case in Scotland through to the second pandemic wave. STUDY DESIGN: The study design of this study is serial cross sectional. METHODS: We tested 41,477 residual samples retrieved from primary and antenatal care settings across Scotland for SARS-CoV-2 antibodies over a 12-month period from December 2019-December 2020 (before rollout of COVID-19 vaccination). Five-weekly rolling seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Temporal trends in seroprevalence estimates and weekly SARS-CoV-2 notifications were compared. RESULTS: Five-weekly rolling seroprevalence rates were 0% until the end of March, when they increased contemporaneously with the first pandemic wave. Seroprevalence rates remained stable through the summer (range: 3%-5%) during a period of social restrictions, after which they increased concurrently with the second wave, reaching 9.6% (95% confidence interval [CI]: 8.4%-10.8%) in the week beginning 28th December in 2020. Seroprevalence rates were lower in rural vs. urban areas (adjusted odds ratio [AOR]: 0.70, 95% CI: 0.61-0.79) and among individuals aged 20-39 years and 60 years and older (AOR: 0.74, 95% CI: 0.64-0.86; AOR: 0.80, 95% CI: 0.69-0.91, respectively) relative to those aged 0-19 years. CONCLUSIONS: After two waves of the COVID-19 pandemic, less than one in ten individuals in the Scottish population had antibodies to SARS-CoV-2. Seroprevalence may underestimate the true population exposure as a result of waning antibodies among individuals who were infected early in the first wave.

Enhanced surveillance of COVID-19 in Scotland: population-based seroprevalence surveillance for SARS-CoV-2 during the first wave of the epidemic.

OBJECTIVES: The impact of the COVID-19 pandemic in Scotland has been amongst the most severe in Europe. Serological surveillance is critical to determine the overall extent of infection across populations and to inform the public health response. This study aimed to estimate the proportion of people who have antibodies to SARS-CoV-2 ('seroprevalence') in the general population of Scotland and to see if this changes over time. STUDY DESIGN/METHODS: Between International Organization for Standardization (ISO) week 17 (i.e. week commencing 20th April) and ISO week 25 (week commencing 15 June), 4751 residual blood samples were obtained from regional biochemistry laboratories in six participating regional health authority areas covering approximately 75% of the Scottish population. Samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies using the LIAISON®SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Italy). Seroprevalence rates were adjusted for the sensitivity and specificity of the assay using Bayesian methods. RESULTS: The combined adjusted seroprevalence across the study period was 4.3% (95% confidence interval: 4.2%-4.5%). The proportion varied each week between 1.9% and 6.8% with no difference in antibody positivity by age, sex or geographical area. CONCLUSIONS: At the end of the first wave of the COVID-19 pandemic, only a small fraction of the Scottish population had antibodies to SARS-CoV-2. Control of COVID-19 requires the ability to detect asymptomatic and mild infections that would otherwise remain undetected through existing surveillance systems. This is important to determine the true number of infections within the general population which, in turn, can help to understand transmission, inform control measures and provide a denominator for the estimation of severity measures such as the proportion of infected people who have been hospitalised and/or have died.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

Late diagnosis of chronic liver disease in a community cohort (UK biobank): determinants and impact on subsequent survival.

BACKGROUND: Chronic liver disease (CLD) is frequently diagnosed at a late stage when prognosis is poor. We aimed to determine the patient factors associated with a late CLD diagnosis and its subsequent impact on survival to support early diagnosis initiatives. METHODS: We identified participants of UK biobank (UKB) study who developed first-time advanced CLD within 5 years. We identified the factors associated with late diagnosis via logistic regression and used survival analysis to measure the association between late CLD diagnosis and mortality risk. RESULTS: A total of 725 UKB participants developed first-time advanced CLD event within 5 years. In total, 83% of cases were diagnosed late. Late diagnosis was associated with aetiology; the odds of late diagnosis were 12 times higher for an individual with alcohol-related liver disease (ArLD) vs viral hepatitis (aOR:12.01; P < 0.001). Cumulative mortality 5 years after incident advanced CLD was 43.4% (95% CI:39.6-47.0). Late diagnosis was associated with a higher risk of postadvanced CLD mortality for patients with non-alcoholic fatty liver disease (aHR:2.18; 95% CI:0.86-5.51; P = 0.10), but not for other aetiologies. CONCLUSIONS: Late CLD diagnosis varies according to aetiology and is highest for patients with ArLD and non-alcoholic fatty liver disease. The association between late diagnosis and postadvanced CLD mortality may also vary by aetiology.

Monitoring response to hepatitis B and C in EU/EEA: testing policies, availability of data on care cascade and chronic viral hepatitis-related mortality - results from two surveys (2016).

OBJECTIVES: The World Health Organization (WHO) developed a European Regional Action Plan (EAP) to fast-track action towards the goal of eliminating viral hepatitis. Robust monitoring is essential to assess national programme performance. The purpose of this study was to assess the availability of selected monitoring data sources in European Union/European Economic Area (EU/EEA) Member States (MS). METHODS: Availability of data sources at EU/EEA level was assessed using two surveys distributed to 31 EU/EEA MS in 2016. The two surveys covered (A) availability of policy documents on testing; testing practices and monitoring; monitoring of diagnosis and treatment initiation, and; (B) availability of data on mortality attributable to chronic viral hepatitis. RESULTS: Just over two-thirds of EU/EEA MS responded to the surveys. 86% (18/21) reported national testing guidance covering HBV, and 81% (17/21) covering HCV; while 33% (7/21) and 38% (8/21) of countries, respectively, monitored the number of tests performed. 71% (15/21) of countries monitored the number of chronic HBV cases diagnosed and 33% (7/21) the number of people treated. Corresponding figures for HCV were 48% (10/21) and 57% (12/21). 27% (6/22) of countries reported availability of data on mortality attributable to chronic viral hepatitis. CONCLUSIONS: The results of this study suggest that sources of information in EU/EEA Member States to monitor the progress towards the EAP milestones and targets related to viral hepatitis diagnosis, cascade of care and attributable mortality are limited. Our analysis should raise awareness among EU/EEA policy makers and stimulate higher prioritisation of efforts to improve the monitoring of national viral hepatitis programmes.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Limited impact of awareness-raising campaigns on hepatitis C testing practices among general practitioners.

The global hepatitis strategy calls for increased effort to diagnose those infected, with a target of 90% diagnosed by 2030. Scotland's Action Plan on Hepatitis C included awareness-raising campaigns, undertaken during 2008-2011, to promote testing by general practitioners. We examined hepatitis C virus (HCV) testing practice among general practitioners before and following these campaigns. Scottish general practitioners were surveyed, using Dillman's method, in 2007 and 2013; response rates were 69% and 60%, respectively. Most respondents offer testing when presented with a risk history (86% in 2007, 88% in 2013) but only one-fifth actively sought out risk factors (19% in 2007, 21% in 2013). Testing was reportedly always/almost always/usually offered to people who inject drugs (84% in 2007, 87% in 2013). Significant improvements in the offer of testing were reported in patients with abnormal LFTs (41% in 2007, 65% in 2013, P<.001) and who had received medical/dental treatment in high prevalence countries (14% in 2007, 24% in 2013, P=.001). In 2013, 25% of respondents had undertaken HCV-related continued professional development. This group was significantly more likely to actively seek out risk factors (P=.009) but only significantly more likely to offer a test to patients who had received medical/dental treatment in high prevalence countries (P=.001). Our findings suggest that government-led awareness raising campaigns have limited impact on general practitioners' testing practices. If the majority of the HCV-infected population are to be diagnosed, practitioner-based or physician-centred interventions should be considered alongside educational initiatives targeted at professionals.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.

A matched comparison study of hepatitis C treatment outcomes in the prison and community setting, and an analysis of the impact of prison release or transfer during therapy.

Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison- and community-based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment-naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%-66%) and 63% (95% CI 60%-66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%-81%), 59% (95% CI 42%-75%) and 45% (95% CI 29%-62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment achieves similar outcomes to community-based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.

Matched population-based study examining the risk of type 2 diabetes in people with and without diagnosed hepatitis C virus infection.

Meta-analyses have found hepatitis C virus (HCV) infection to be associated with an increased risk of type 2 diabetes mellitus (T2DM). Here, we examine this association within a large population-based study, according to HCV RNA status. A data-linkage approach was used to examine the excess risk of diagnosed T2DM in people diagnosed with antibodies to HCV (anti-HCV) in Scotland (21 929 anti-HCV(+ves) ; involving 15 827 HCV RNA(+ves) , 3927 HCV RNA(-ves) and 2175 with unknown RNA-status) compared to that of a threefold larger general population sample matched for gender, age and postcode (65 074 anti-HCV(-ves) ). To investigate effects of ascertainment bias the following periods were studied: up to 1 year before (pre-HCV)/within 1 year of (peri-HCV)/more than 1 year post (post-HCV) the date of HCV-diagnosis. T2DM had been diagnosed in 2.9% of anti-HCV(+ves) (including 3.2% of HCV RNA(+ves) and 2.3% of HCV RNA(-ves) ) and 2.7% of anti-HCV(-ves) . A higher proportion of T2DM was diagnosed in the peri-HCV period (i.e. around the time of HCV-diagnosis) for the anti-HCV(+ves) (22%) compared to anti-HCV(-ves) (10%). In both the pre-HCV and post-HCV periods, only those anti-HCV(+ves) living in less deprived areas (13% of the cohort) were found to have a significant excess risk of T2DM compared to anti-HCV(-ves) (adjusted odds ratio in the pre-HCV period: 4.0 for females and 2.3 for males; adjusted hazard ratio in the post-HCV period: 1.5). These findings were similarly observed for both HCV RNA(+ves) (chronic) and HCV RNA(-ves) (resolved). In the largest study of T2DM among chronic HCV-infected individuals to date, there was no evidence to indicate that infection conveyed an appreciable excess risk of T2DM at the population level.

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.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.

Estimating the number of injecting drug users in Scotland's HCV-diagnosed population using capture-recapture methods.

In countries maintaining national hepatitis C virus (HCV) surveillance systems, a substantial proportion of individuals report no risk factors for infection. Our goal was to estimate the proportion of diagnosed HCV antibody-positive persons in Scotland (1991-2010) who probably acquired infection through injecting drug use (IDU), by combining data on IDU risk from four linked data sources using log-linear capture-recapture methods. Of 25,521 HCV-diagnosed individuals, 14,836 (58%) reported IDU risk with their HCV diagnosis. Log-linear modelling estimated a further 2484 HCV-diagnosed individuals with IDU risk, giving an estimated prevalence of 83. Stratified analyses indicated variation across birth cohort, with estimated prevalence as low as 49% in persons born before 1960 and greater than 90% for those born since 1960. These findings provide public-health professionals with a more complete profile of Scotland's HCV-infected population in terms of transmission route, which is essential for targeting educational, prevention and treatment interventions.

Pulmonary outflow tract obstruction in fetuses with complex congenital heart disease: predicting the need for neonatal intervention.

OBJECTIVE: To identify prenatal echocardiographic markers that could predict the need for neonatal intervention in fetuses with right ventricular outflow tract obstruction. METHODS: This was a retrospective study of 52 fetuses with right ventricular outflow tract obstruction. Echocardiograms were evaluated for fetuses with either two-ventricle anatomy with a large ventricular septal defect or single-ventricle anatomy. Fetuses with pulmonary atresia were excluded. Parameters were compared between groups that did and did not require an intervention at age < 30 days. RESULTS: Fifty-two fetuses were studied; 20 (38%) underwent neonatal intervention and 32 (62%) did not. The most common diagnosis was tetralogy of Fallot (n = 32). Fetuses with two ventricles that required an intervention had lower pulmonary valve diameter Z-score (PV-Z-score) (-4.8 ± 2.1 vs. -2.6 ± 1.1; P = 0.0002) and lower pulmonary valve to aortic valve annular diameter ratio (PV/AoV) (0.53 ± 0.15 vs. 0.66 ± 0.1; P = 0.003). Using a PV/AoV ratio of < 0.6 or a PV-Z-score of < -3 at final echocardiographic examination was highly sensitive (92%) but poorly specific (50%), whereas classifying direction of flow in the ductus arteriosus as either normal (all pulmonary-to-aorta) or abnormal (aorta-to-pulmonary or bidirectional) was both highly sensitive (100%) and specific (95%) for predicting the need for a neonatal intervention. Parameters for the single-ventricle cohort did not reach statistical significance. CONCLUSIONS: Analysis of the pulmonary outflow tract and ductus arteriosus flow in the fetus with complex congenital heart disease can aid in identifying those that will require a neonatal intervention to augment pulmonary blood flow. This has important implications for the planning of delivery strategies.

Identifying former injecting drug users infected with hepatitis C: an evaluation of a general practice-based case-finding intervention.

BACKGROUND: In Scotland, a general practice-based case-finding initiative, to diagnose and refer hepatitis C virus (HCV) chronically infected former injecting drug users (IDUs), was evaluated. METHODS: Testing was offered in eight Glasgow general practices in areas of high deprivation and high HCV and IDU prevalence to attendees aged 30-54 years with a history of IDU. Test uptake and diagnosis rates were compared with those in eight demographically similar control practices. RESULTS: Of 422 eligible intervention practice attendees, 218 (52%) were offered an HCV test and, of these, 121 (56%) accepted. Poor venous access in 13 individuals prevented testing. Of 105 tested, 70% (74/105) were antibody positive of which 58% (43/74) were RNA positive by PCR. Of 43 chronically infected individuals identified in intervention practices, 22 (51%) had attended specialist care within 30 months of the study, while 9 (21%) had defaulted. In control practices, 8 (22%) of 36 individuals tested were antibody positive. Test uptake and case yield were approximately 3 and 10 times higher in intervention compared with control practices, respectively. CONCLUSIONS: Targeted case-finding in primary care demonstrated higher test uptake and diagnosis rates; however, to optimize diagnosis and referral of chronically infected individuals, alternative means of testing (e.g. dried blood spots) and retention in specialist care (e.g. outreach services) must be explored.