Impact of the COVID-19 Pandemic on HIV Test Uptake Among People Who Inject Drugs in the Context of an HIV Outbreak.

Glasgow, Scotland's largest city, has been experiencing an HIV outbreak among people who inject drugs (PWID) since 2015. A key focus of the public health response has been to increase HIV testing among those at risk of infection. Our aim was to assess the impact of COVID-19 on HIV testing among PWID in Glasgow. HIV test uptake in the last 12 months was quantified among: (1) PWID recruited in six Needle Exchange Surveillance Initiative (NESI) surveys (n = 6110); linked laboratory data for (2) people prescribed opioid agonist therapy (OAT) (n = 14,527) and (3) people hospitalised for an injecting-related hospital admission (IRHA) (n = 12,621) across four time periods: pre-outbreak (2010-2014); early-outbreak (2015-2016); ongoing-outbreak (2017-2019); and COVID-19 (2020-June 21). From the pre to ongoing period, HIV testing increased: the highest among people recruited in NESI (from 28% to 56%) and on OAT (from 17% to 54%) while the lowest was among people with an IRHA (from 15% to 42%). From the ongoing to the COVID-19 period, HIV testing decreased markedly among people prescribed OAT, from 54% to 37% (aOR 0.50, 95% CI 0.48-0.53), but increased marginally among people with an IRHA from 42% to 47% (aOR 1.19, 95% CI 1.08-1.31). In conclusion, progress in increasing testing in response to the HIV outbreak has been eroded by COVID-19. Adoption of a linked data approach could be warranted in other settings to inform efforts to eliminate HIV transmission.

Prevalence of opioid dependence in Scotland 2015-2020: A multi-parameter estimation of prevalence (MPEP) study.

BACKGROUND AND AIMS: Drug-related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15-64 from 2014/15 to 2019/20. DESIGN: We fitted a Bayesian multi-parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid-related mortality and hospital admissions data. Estimates are stratified by age group, sex and year. SETTING: Scotland, 2014/15 to 2019/20. PARTICIPANTS: People with opioid dependence and potential to benefit from OAT, whether ever treated or not. Using data from the Scottish Public Health Drug Linkage Programme, we identified a baseline cohort of individuals who had received OAT within the last 5 years, and all opioid-related deaths and hospital admissions (whether among or outside of this cohort). MEASUREMENTS: Rates of each adverse event type and (unobserved) prevalence were jointly modelled. FINDINGS: The estimated number and prevalence of people with opioid dependence in Scotland in 2019/20 was 47 100 (95% Credible Interval [CrI] 45 700 to 48 600) and 1.32% (95% CrI 1.28% to 1.37%). Of these, 61% received OAT during 2019/20. Prevalence in Greater Glasgow and Clyde was estimated as 1.77% (95% CrI 1.69% to 1.85%). There was weak evidence that overall prevalence fell slightly from 2014/15 (change -0.07%, 95% CrI -0.14% to 0.00%). The population of people with opioid dependence is ageing, with the estimated number of people aged 15-34 reducing by 5100 (95% CrI 3800 to 6400) and number aged 50-64 increasing by 2800 (95% CrI 2100 to 3500) between 2014/15 and 2019/20. CONCLUSIONS: The prevalence of opioid dependence in Scotland remained high but was relatively stable, with only weak evidence of a small reduction, between 2014/15 and 2019/20. Increased numbers of opioid-related deaths can be attributed to increased risk among people with opioid dependence, rather than increasing prevalence.

SARS-CoV-2 vaccine uptake and risks of severe COVID-19 disease among people prescribed opioid agonist therapy in Scotland.

BACKGROUND: There is limited evidence quantifying the risk of severe COVID-19 disease among people with opioid dependence. We examined vaccine uptake and severe disease (admission to critical care or death with COVID-19) among individuals prescribed opioid agonist therapy (OAT). METHOD: A case-control design was used to examine vaccine uptake in those prescribed OAT compared with the general population, and the association between severe disease and OAT. In both analyses, 10 controls from the general population were matched (to each OAT recipient and COVID-19 case, respectively) according to socio-demographic factors. Conditional logistic regression was used to estimate rate ratios (RR) for severe disease. RESULTS: Vaccine uptake was markedly lower in the OAT cohort (dose 1: 67%, dose 2: 53% and dose 3: 31%) compared with matched controls (76%, 72% and 57%, respectively). Those prescribed OAT within the last 5 years, compared with those not prescribed, had increased risk of severe COVID-19 (RR 3.38, 95% CI 2.75 to 4.15), particularly in the fourth wave (RR 6.58, 95% CI 4.20 to 10.32); adjustment for comorbidity and vaccine status attenuated this risk (adjusted RR (aRR) 2.43, 95% CI 1.95 to 3.02; wave 4 aRR 3.78, 95% CI 2.30 to 6.20). Increased risk was also observed for those prescribed OAT previously (>3 months ago) compared with recently (aRR 1.74, 95% CI 1.11 to 2.71). CONCLUSIONS: The widening gap in vaccine coverage for those prescribed OAT, compared with the general population, is likely to have exacerbated the risk of severe COVID-19 in this population over the pandemic. However, continued OAT use may have provided protection from severe COVID-19 among those with opioid dependence.

A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: Self-controlled case-series analysis of national data.

BACKGROUND AND AIMS: Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs. DESIGN: This was a self-controlled case-series study. SETTING: Scotland, 1 January 2015-30 November 2020. PARTICIPANTS: The study population of non-cirrhotic, DAA-treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day-case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non-viral injecting related admission and drug-related mortality) were defined using ICD codes. MEASUREMENTS: Self-controlled case-series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90-day exposure risk periods thereafter. FINDINGS: A total of 6050 PWID were treated with DAAs in the sampling time-frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80-0.99; 0.89, 95% CI = 0.80-0.99; 0.86, 95% CI = 0.77-0.96; 0.88, 95% CI = 0.78-0.99, respectively]. For non-viral injecting-related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64-0.90; 0.75, 95% CI = 0.62-0.90; 0.79, 95% CI = 0.66-0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end. CONCLUSIONS: Among people who inject drugs in Scotland, direct-acting antiviral treatment appears to be associated with a small, non-durable reduction in the risk of drug-related hospital admission, but not drug-related mortality. Direct-acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug-related health harms.

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study.

OBJECTIVES: To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population. DESIGN: Population based cohort study. SETTING: British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only). PARTICIPANTS: 21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019. MAIN OUTCOME MEASURES: Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates. RESULTS: 1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates. CONCLUSION: Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.

Mortality among individuals prescribed opioid-agonist therapy in Scotland, UK, 2011-20: a national retrospective cohort study.

BACKGROUND: Drug-related death (DRD) rate in Scotland, UK, has increased rapidly to one of the highest in the world. Our aim was to examine the extent to which opioid-agonist therapy (OAT) in Scotland is protective against drug-related mortality and how this effect has varied over time. METHODS: We included individuals in Scotland with opioid use disorder who received at least one OAT prescription between Jan 1, 2011, and Dec 31, 2020. We calculated drug-related mortality rates and used Quasi-Poisson regression models to estimate trends over time and by OAT exposure, adjusting for potential confounding. FINDINGS: In a cohort of 46 453 individuals prescribed OAT with a total of 304 000 person-years of follow-up, DRD rates more than trebled from 6·36 per 1000 person-years (95% CI 5·73-7·01) in 2011-12 to 21·45 (20·31-22·63) in 2019-20. DRD rates were almost three and a half times higher (hazard ratio 3·37; 95% CI 1·74-6·53) for those off OAT compared with those on OAT after adjustment for confounders. However, confounder adjusted DRD risk increased over time for both people off and on OAT. INTERPRETATION: Drug-related mortality rates among people with opioid use disorders in Scotland increased between 2011 and 2020. OAT remains protective but is insufficient on its own to slow the increase in DRD risk for people who are opioid dependent in Scotland. FUNDING: Scottish Government Drug Deaths Taskforce, Public Health Scotland, and National Institute for Health and Care Research.

Geographical variation in hepatitis C-related severe liver disease and patient risk factors: a multicentre cross-sectional study.

Despite promising steps towards the elimination of hepatitis C virus (HCV) in the UK, several indicators provide a cause for concern for future disease burden. We aimed to improve understanding of geographical variation in HCV-related severe liver disease and historic risk factor prevalence among clinic attendees in England and Scotland. We used metadata from 3829 HCV-positive patients consecutively enrolled into HCV Research UK from 48 hospital centres in England and Scotland during 2012-2014. Employing mixed-effects statistical modelling, several independent risk factors were identified: age 46-59 y (ORadj 3.06) and ≥60 y (ORadj 5.64) relative to <46 y, male relative to female sex (ORadj 1.58), high BMI (ORadj 1.73) and obesity (ORadj 2.81) relative to normal BMI, diabetes relative to no diabetes (ORadj 2.75), infection with HCV genotype (GT)-3 relative to GT-1 (ORadj 1.75), route of infection through blood products relative to injecting drug use (ORadj 1.40), and lower odds were associated with black ethnicity (ORadj 0.31) relative to white ethnicity. A small proportion of unexplained variation was attributed to differences between hospital centres and local health authorities. Our study provides a baseline measure of historic risk factor prevalence and potential geographical variation in healthcare provision, to support ongoing monitoring of HCV-related disease burden and the design of risk prevention measures.

Improved health-related quality of life after hepatitis C viraemic clearance among people who inject drugs may not be durable.

BACKGROUND AND AIMS: Chronic infection with the hepatitis C virus (HCV) has a detrimental impact on health-related quality of life (QoL). Scale-up of HCV direct-acting antiviral (DAA) therapy among people who inject drugs (PWID) is underway in several countries since the introduction of interferon-free regimens. This study aimed to assess the impact of DAA treatment success on QoL for PWID. DESIGN: Cross-sectional study using two rounds of the Needle Exchange Surveillance Initiative, a national anonymous bio-behavioural survey and a longitudinal study involving PWID who underwent DAA therapy. SETTING: The setting for the cross-sectional study was Scotland (2017-2018, 2019-2020). The setting for the longitudinal study was the Tayside region of Scotland (2019-2021). PARTICIPANTS: In the cross-sectional study PWID were recruited from services providing injecting equipment (n = 4009). In the longitudinal study, participants were PWID on DAA therapy (n = 83). MEASUREMENTS: In the cross-sectional study, the association between QoL (measured using the EQ-5D-5L quality of life instrument) and HCV diagnosis and treatment was assessed using multilevel linear regression. In the longitudinal study, QoL was compared at four timepoints using multilevel regression, from treatment commencement until 12 months following commencement. FINDINGS: In the cross-sectional study, 41% (n = 1618) were ever chronically HCV infected, of whom 78% (n = 1262) were aware of their status and of whom 64% (n = 704) had undergone DAA therapy. There was no evidence for a marked QoL improvement associated with viral clearance among those treated for HCV (B = 0.03; 95% CI, -0.03 to 0.09). In the longitudinal study, improved QoL was observed at the sustained virologic response test timepoint (B = 0.18; 95% CI, 0.10-0.27), but this was not maintained at 12 months following start of treatment (B = 0.02; 95% CI, -0.05 to 0.10). CONCLUSIONS: Successful direct-acting antiviral therapy for hepatitis C infection may not lead to a durable improvement in quality of life among people who inject drugs, although there may be a transient improvement around the time of sustained virologic response. Economic models of the impact of scaling-up treatment may need to include more conservative quality of life benefits over and above reductions in mortality, disease progression and transmission of infection.

Laying the foundations for hepatitis C elimination: evaluating the development and contribution of community care pathways to diagnostic efforts.

BACKGROUND: Hepatitis C Virus (HCV) is a public health threat which contributes substantially to the global burden of liver disease. There is much debate about effective approaches to scaling up diagnosis of HCV among risk groups. Tayside, a region in the East of Scotland, developed low-threshold community pathways for HCV to lay the foundations of an elimination strategy. In this retrospective study, we sought to: quantify the contribution of community pathways to increasing HCV diagnosis; understand if shifting diagnosis to community settings led to a higher proportion of individuals tested for HCV being actively infected; and describe functional characteristics of the care pathways. METHODS: Descriptive statistics were used to for analysis of routinely-collected HCV testing data from 1999 to 2017, and a review of the development of the care pathways was undertaken. Community-based testing was offered through general practices (GP); nurse outreach clinics; prisons; drug treatment services; needle and syringe provision (NSP) sites; community pharmacies; and mosques. RESULTS: Anti-HCV screening was undertaken on 109,430 samples, of which 5176 (4.7%) were reactive. Of all samples, 77,885 (71.2%) were taken in secondary care; 25,044 (22.9%) in GPs; 2970 (2.7%) in prisons; 2415 (2.2%) in drug services; 753 (0.7%) in NSPs; 193 (0.2%) pharmacies; and 170 (0.1%) in mosques. The highest prevalence of HCV infection among those tested was in NSP sites (26%), prisons (14%), and drug treatment centres (12%). CONCLUSIONS: Decentralised care pathways, particularly in harm reduction and other drug service settings, were key to increasing diagnosis of HCV in the region, but primary and secondary care remain central to elimination efforts.

Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK.

BACKGROUND: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK. METHODS: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource. Data on (i) liver/abdominal US examinations, (ii) HCC diagnoses, and (iii) HCC curative treatment were obtained through record-linkage to national health registries. The rate of US uptake was calculated by dividing the number of US episodes by follow-up time. RESULTS: A total of 1908 cirrhosis patients from 31 liver centres were followed for 3.8 (IQR: 3.4-4.9) years. Overall, 10 396 liver/abdominal USs were identified. The proportion with biannual US was 19% in the first 3 years after SVR and 9% for all follow-up years. Higher uptake of biannual US was associated with attending a liver transplant centre; older age and cirrhosis decompensation. Funnel plot analysis indicated significant inter-centre variability in biannual US uptake, with 6/29 centres outside control limits. Incident HCC occurred in 133 patients, of which 49/133 (37%) were treated with curative intent. The number of US episodes in the two years prior to HCC diagnosis was significantly associated with higher odds of curative-intent treatment (aOR: 1.53; 95% CI: 1.12-2,09; p = .007). CONCLUSIONS: This study provides novel data on the cascade of care for HCC in the UK. Our findings suggest biannual US is poorly targeted, inefficient and is not being delivered equitably to all patients.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Interventions to prevent HIV and Hepatitis C among people who inject drugs: Latest evidence of effectiveness from a systematic review (2011 to 2020).

BACKGROUND: Hepatitis C virus (HCV) and HIV remain prevalent among people who inject drugs (PWID) and transmission is usually associated with injecting risk behaviour (IRB). We update a 2011 review of reviews (RoR) to assess the latest evidence on the effectiveness of harm reduction interventions - drug treatment (including opioid agonist therapy [OAT]), needle and syringe programmes (NSP) and other interventions - in the prevention of HCV and HIV transmission, and related measures of infection risk (IRB and injecting frequency [IF]), among PWID. METHODS: We undertook an initial search for systematic reviews (i.e. an Overview of Reviews [OoR]) and subsequent systematic searches for primary studies where required. Where there was sufficient evidence based on synthesis of multiple robust studies for an intervention effect in the 2011 RoR, new evidence was not sought. Medline, CINAHL, The Cochrane Library, EMBASE, PsycINFO and Web of Science were searched (2011-2020). Two reviewers screened papers, extracted data, and graded reviews/studies. We classified evidence as 'sufficient', 'tentative', 'insufficient', or 'no evidence'. RESULTS: We screened 8513 reviews and 7133 studies, with 27 and 61 identified as relevant, respectively. The level of evidence increased since the 2011 RoR and is now 'sufficient' for OAT (regarding all outcomes), NSP (for reducing HIV transmission and IRB), and combination OAT/NSP (for reducing HCV transmission). There is also now sufficient evidence for in-prison OAT, psychosocial interventions, pharmacy-based NSP and provision of sterile drug preparation equipment for reducing IRB. CONCLUSION: There is now a strong body of empirical evidence for the effectiveness of OAT and NSP, alone and in combination, in reducing IRB, and HCV and HIV transmission. However, there is still a relative lack of evidence for other interventions, including heroin-assisted treatment, pharmacological treatment for stimulant dependence, contingency management, technology-based interventions, low dead space syringes and drug consumption rooms on HCV or HIV risk.

Comparing Predicted Probability of Hepatocellular Carcinoma in Patients With Cirrhosis With the General Population: An Opportunity to Improve Risk Communication?

INTRODUCTION: Risk scores estimating a patient's probability of a hepatocellular carcinoma (HCC) diagnosis are abundant but are difficult to interpret in isolation. We compared the predicted HCC probability for individuals with cirrhosis and cured hepatitis C with the general population (GP). METHODS: All patients with cirrhosis achieving sustained viral response (SVR) in Scotland by April 2018 were included (N = 1,803). The predicted 3-year probability of HCC at time of SVR achievement was determined using the aMAP prognostic model. GP data on the total number of incident HCCs in Scotland, stratified by demographics, were obtained from Public Health Scotland. Predicted HCC risk of cirrhosis SVR patients was compared with GP incidence using 2 metrics: (i) incidence ratio: i.e., 3-year predicted probability for a given patient divided by the 3-year probability in GP for the equivalent demographic group and (ii) absolute risk difference: the 3-year predicted probability minus the 3-year probability in the GP. RESULTS: The mean predicted 3-year HCC probability among cirrhosis SVR patients was 3.64% (range: 0.012%-36.12%). Conversely, the 3-year HCC probability in the GP was much lower, ranging from <0.0001% to 0.25% depending on demographics. The mean incidence ratio was 410, ranging from 5 to >10,000. The mean absolute risk difference was 3.61%, ranging from 0.012% to 35.9%. An online HCC-GP comparison calculator for use by patients/clinicians is available at https://thrive-svr.shinyapps.io/RShiny/ . DISCUSSION: Comparing a patient's predicted HCC probability with the GP is feasible and may help clinicians communicate risk information and encourage screening uptake.

Supporting safe and gradual reduction of long-term benzodiazepine receptor agonist use: Development of the SAFEGUARDING-BZRAs toolkit using a codesign approach.

INTRODUCTION: Long-term benzodiazepine receptor agonist (BZRA) use persists in healthcare settings worldwide and poses risks of patient harm. OBJECTIVE: This study aimed to develop an intervention to support discontinuation of long-term BZRA use among willing individuals. METHODS: The intervention development process aligned with the UK Medical Research Council's complex intervention framework. This involved a previous systematic review of brief interventions targeting long-term BZRA use in primary care and qualitative interviews based on the Theoretical Domains Framework that explored barriers and facilitators to discontinuing long-term BZRA use. A codesign approach was used involving an active partnership between experts by experience, researchers and clinicians. Intervention content was specified in terms of behaviour change techniques (BCTs). RESULTS: The SAFEGUARDING-BZRAs (Supporting sAFE and GradUAl ReDuctIon of loNG-term BenZodiazepine Receptor Agonist uSe) toolkit comprises 24 BCTs and includes recommendations targeted at primary care-based clinicians for operationalizing each BCT to support individuals with BZRA discontinuation. CONCLUSION: The SAFEGUARDING-BZRAs toolkit has been developed using a systematic and theory-based approach that addresses identified limitations of previous research. Further research is needed to assess its usability and acceptability by service users and clinicians, as well as its potential to effectively support safe and gradual reduction of long-term BZRA use. PATIENT OR PUBLIC CONTRIBUTION: The qualitative interview phase included patients as participants. The codesign process included 'experts by experience' with either current or previous experience of long-term BZRA use as collaborators.

Vaccine efficacy against severe COVID-19 in relation to delta variant (B.1.617.2) and time since second dose in patients in Scotland (REACT-SCOT): a case-control study.

BACKGROUND: Reports have suggested that the efficacy of vaccines against COVID-19 might have fallen since the delta (B.1.617.2) SARS-CoV-2 variant replaced the alpha (B.1.1.7) variant as the predominant variant. We aimed to investigate, for the two main classes of vaccine, whether efficacy against severe COVID-19 has decreased since delta became the predominant variant and whether the efficacy of two doses of vaccine against severe COVID-19 wanes with time since second dose. METHODS: In the REACT-SCOT case-control study, vaccine efficacy was estimated using a matched case-control design that includes all diagnosed cases of COVID-19 in Scotland up to Sept 8, 2021. For every incident case of COVID-19 in the Scottish population, ten controls matched for age rounded to the nearest year, sex, and primary care practice, and alive on the day of presentation of the case that they were matched to were selected using the Community Health Index database. To minimise ascertainment bias we prespecified the primary outcome measure to assess vaccine efficacy as severe COVID-19, defined as diagnosed patients with entry to critical care within 21 days of first positive test, death within 28 days of first positive test, or any death for which COVID-19 was coded as underlying cause. Although the data extracted for this study included cases presenting up to Sept 22, 2021, the analyses reported here are restricted to cases and controls presenting from Dec 1, 2020, to Sept 8, 2021, ensuring follow-up for at least 14 days after presentation date to allow classification of hospitalisation and (for most cases) severity based on entry to critical care or fatal outcome. FINDINGS: During the study period, a total of 5645 severe cases of COVID-19 were recorded; these were matched to 50 096 controls. Of the severe cases, 4495 (80%) were not vaccinated, and of the controls, 36 879 (74%) were not vaccinated. Of the severe cases of COVID-19 who had been vaccinated, 389 had received an mRNA vaccine and 759 had received the ChAdOx1 vaccine. The efficacy of vaccination against severe COVID-19 decreased in May, 2021, coinciding with the replacement of the alpha SARS-CoV-2 variant by the delta variant in Scotland, but this decrease was reversed over the following month. In the most recent time window centred on July 29, 2021, the efficacy of two doses was 91% (95% CI 87-94) for the ChAdOx1 vaccine and 92% (88-95) for mRNA (Pfizer or Moderna) vaccines. The efficacy of the ChAdOx1 vaccine against severe COVID-19 declined with time since second dose to 69% (95% CI 52-80) at 20 weeks from second dose. The efficacy of mRNA vaccines declined in the first ten weeks from second dose but more slowly thereafter to 93% (88-96) at 20 weeks from second dose. INTERPRETATION: Our results are reassuring with respect to concerns that vaccine efficacy against severe COVID-19 might have fallen since the delta variant became predominant, or that efficacy of mRNA vaccines wanes within the first 5-6 months after second dose. However, the efficacy of the ChAdOx1 vaccine against severe COVID-19 wanes substantially by 20 weeks from second dose. Efficacy of mRNA vaccines after 20 weeks and against newer variants remains to be established. Our findings support the case for additional protective measures for those at risk of severe disease, including, but not limited to, booster doses, at times when transmission rates are high or expected to rise. FUNDING: None.

Examining the impact of the first wave of COVID-19 and associated control measures on interventions to prevent blood-borne viruses among people who inject drugs in Scotland: an interrupted time series study.

BACKGROUND: COVID-19 has likely affected the delivery of interventions to prevent blood-borne viruses (BBVs) among people who inject drugs (PWID). We examined the impact of the first wave of COVID-19 in Scotland on: 1) needle and syringe provision (NSP), 2) opioid agonist therapy (OAT) and 3) BBV testing. METHODS: An interrupted time series study design; 23rd March 2020 (date of the first 'lockdown') was chosen as the key date. RESULTS: The number of HIV tests and HCV tests in drug services/prisons, and the number of needles/syringes (N/S) distributed decreased by 94% (RR=0.062, 95% CI 0.041-0.094, p < 0.001), 95% (RR=0.049, 95% CI 0.034-0.069, p < 0.001) and 18% (RR = 0.816, 95% CI 0.750-0.887, p < 0.001), respectively, immediately after lockdown. Post-lockdown, an increasing trend was observed relating to the number of N/S distributed (0.6%; RR = 1.006, 95% CI 1.001-1.012, p = 0.015), HIV tests (12.1%; RR = 1.121, 95% CI 1.092-1.152, p < 0.001) and HCV tests (13.2%; RR = 1.132, 95 CI 1.106-1.158, p < 0.001). Trends relating to the total amount of methadone prescribed remained stable, but a decreasing trend in the number of prescriptions (2.4%; RR = 0.976, 95% CI 0.959-0.993, p = 0.006) and an increasing trend in the quantity prescribed per prescription (2.8%; RR = 1.028, 95% CI 1.013-1.042, p < 0.001) was observed post-lockdown. CONCLUSIONS: COVID-19 impacted the delivery of BBV prevention services for PWID in Scotland. While there is evidence of service recovery; further effort is likely required to return some intervention coverage to pre-pandemic levels in the context of subsequent waves of COVID-19.

Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis.

INTRODUCTION: Risk-stratifying patients with hepatitis C virus (HCV) cirrhosis according to medium-term prognosis will inform clinical decision-making. It is unclear which biomarkers/models are optimal for this purpose. We quantified the discriminative ability of 14 diverse biomarkers for prognosis prediction over a 4-year time. METHODS: We recruited 1196 patients with HCV cirrhosis from the United Kingdom for a prospective study. Genetic risk score, collagen (e.g., PROC3), comorbidity (e.g., CirCom), and validated biomarkers from routine data were measured at enrollment. Participants were linked to UK hospital admission, cancer, and mortality registries. Primary endpoints were (i) liver-related outcomes for patients with compensated cirrhosis and (ii) all-cause mortality for decompensated cirrhosis. The discriminative ability of all biomarkers was quantified individually and also by the fraction of new prognostic information provided. RESULTS: At enrollment, 289 (24%) and 907 (76%) had decompensated and compensated cirrhosis, respectively. Participants were followed for 3-4 years on average, with >70% of the follow-up time occurring post-HCV cure. Seventy-five deaths in the decompensated subgroup and 98 liver-related outcomes in the compensated subgroup were reported. The discriminative ability of the albumin-bilirubin-fibrosis-4 index (C-index: 0.71-0.72) was superior to collagen biomarkers (C-index = 0.58-0.67), genetic risk scores (C-index = 0.50-0.57), and comorbidity markers (0.53-0.60). Validated biomarkers showed the greatest prognostic improvement when combined with a comorbidity or a collagen biomarker (generally >30% of new prognostic information added). DISCUSSION: Inexpensive biomarkers such as the albumin-bilirubin-fibrosis-4 index predict medium-term cirrhosis prognosis moderately well and outperform collagen, genetic, and comorbidity biomarkers. Improvement of performance was greatest when a validated test was combined with comorbidity or collagen biomarker.