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IntroductionThe COVID 19 pandemic presented a challenge to UK hepatology services to devise new strategies to provide safe and effective outpatient care.1 Most patients could be managed remotely via virtual clinics but a cohort of patients with advanced liver disease need more direct monitoring and assessment.1 We describe a new hepatology ambulatory care unit set up during Covid-19 in a tertiary liver unit and demonstrate its outcomes.MethodThe Hepatology Ambulatory Unit (HAU) was managed by two clinical registrars assessing patients face to face (F2F) with daily consultant supervision, supported by a registered nurse and two medical student volunteers acting as health care assistants. F2F and virtual clinic reviews were offered. Patients were referred into the HAU from local GPs, consultant referrals, following ward discharge and via a direct patient hot line triaged by two clinical nurse specialists.ResultsData were collected from 23rd March to 23rd June 2020, comprising 136 patient encounters. 86 patient encounters were completed in the F2F, the remainder in the virtual clinic. 67% of patients were females and 56% had decompensated cirrhosis in the F2F clinic, with alcohol the most common aetiology (41%).The rest of the patients has a mixture of non- cirrhotic aetiology. 14 patients needed paracentesis and 4 patients had infusions (blood or iron). Of the patients with cirrhosis, 83% had Child – Pugh Score B (7–9) and 14% had Child Pugh C (10–15), 56% had a UKELD between 49–60. Majority of the patients were followed up in the consultant led virtual clinic (65%) and HAU virtual clinic (25%). One patient underwent a liver transplant and 2 patients were referred to other specialist clinics. 3 patients were discharged to the GP. There were 2 patients admitted directly to the hospital with variceal bleed and sepsis. None of the patients within the HAU clinic were infected with Covid-19, and there were no deaths.ConclusionOur study shows that patients with advanced liver disease can be safely managed as outpatients in a well-supported closely-monitored unit. Given reports of significantly increased Covid-19 related morbidity and mortality in patients with cirrhosis,1 we have demonstrated an alternative and effective ambulatory model of care, which can be retained to deliver safe care to this vulnerable patient group in the future.Conflicts of InterestThe authors have no conflicts of interest or competing interests to disclose.Referencehttps://www.journal-of-hepatology.eu/article/S0168-8278(20)30305-6/fulltext

BackgroundOn World AIDS Day 2021, the UK Government committed £20 million to expand opt-out HIV testing in EDs in extremely high HIV prevalence (>5/1000) areas as part of their commitment to achieve zero new HIV infections, AIDS and HIV-related deaths by 2030. 34 EDs in London, Brighton, Greater Manchester and Blackpool were included. The initiative started in April 2022 and expanded to include hepatitis C (HCV) and hepatitis B (HBV) testing in collaboration with the HCV Elimination programme.MethodsAll adults undergoing blood tests in EDs had BBV testing (4th generation HIV test, HBV surface antigen and HCV antibody with reflex RNA if HCV antibody positive) unless they opted out. An opt-out approach was taken, based on successful pilots, to maximise uptake and minimise impact on ED workload. Testing information was displayed using accessible and translated posters in EDs. HIV/Sexual Health and Hepatology managed all reactive/positive results.ResultsBy March 2023, 33 EDs had implemented HIV testing, 25 HCV and 19 HBV. From April 2022 through March 2023 there were 1,384,378 adult ED attendances with blood tests and 853,015 HIV, 346,041 HBV and 452,284 HCV tests were performed. Median test uptake increased from 51.1% (HIV), 16.3% (HBV), 23.7% (HCV) in April 2022 to 62% (HIV), 57% (HBV) and 62% (HCV) in March 2023.ED opt-out BBV testing identified 2002 people who were newly diagnosed (343 HIV, 1190 HBV, 484 HCV) and 473 who were previously diagnosed but not in care (HIV 209, HBV 156, HCV 108). Initial linkage to care was 339/552 (61%) for HIV (268/343 (78%) for new HIV diagnoses), 329/1346 (24%) for HBV and 292/592 (49%) for HCV.ConclusionsOpt-out BBV testing in EDs has proven extremely effective for making new BBV diagnoses and re-engaging those previously diagnosed but not in care. We found very high rates of HBV. Initial linkage to care is encouraging and is expected to increase over time.

Gene vectors to treat cystic fibrosis lung disease should be targeted to the conducting airways, as peripheral lung transduction does not offer therapeutic benefit. Viral transduction efficiency is directly related to the vector residence time. However, delivered fluids such as gene vectors naturally spread to the alveoli during inspiration, and therapeutic particles of any form are rapidly cleared via mucociliary transit. Extending gene vector residence time within the conducting airways is important, but hard to achieve. Gene vector conjugated magnetic particles that can be guided to the conducting airway surfaces could improve regional targeting. Due to the challenges of in-vivo visualisation, the behaviour of such small magnetic particles on the airway surface in the presence of an applied magnetic field is poorly understood. The aim of this study was to use synchrotron imaging to visualise the in-vivo motion of a range of magnetic particles in the trachea of anaesthetised rats to examine the dynamics and patterns of individual and bulk particle behaviour in-vivo. We also then assessed whether lentiviral-magnetic particle delivery in the presence of a magnetic field increases transduction efficiency in the rat trachea. Synchrotron X-ray imaging revealed the behaviour of magnetic particles in stationary and moving magnetic fields, both in-vitro and in-vivo. Particles could not easily be dragged along the live airway surface with the magnet, but during delivery deposition was focussed within the field of view where the magnetic field was the strongest. Transduction efficiency was also improved six-fold when the lentiviral-magnetic particles were delivered in the presence of a magnetic field. Together these results show that lentiviral-magnetic particles and magnetic fields may be a valuable approach for improving gene vector targeting and increasing transduction levels in the conducting airways in-vivo.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants younger than 6 months, resulting in an estimated 1·4 million hospital admissions each year worldwide. 1 A maternal bivalent RSV prefusion F protein-based (RSVpreF) vaccine was introduced to routine immunisation schedules from Aug 12, 2024, in Scotland, and Sept 1, 2024, in England. Public health agencies should aim to bolster this confidence with the timely release of results of vaccine safety data at a national scale. Future efforts in the UK should focus on streamlining access to the RSVPreF vaccination for pregnant women and raising awareness of both the vaccination and RSV disease in infants.

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

The National Health Service (NHS) Long Term Plan, published in 2019, committed to ensuring that every patient in England has the right to digital-first primary care by 2023-2024. The COVID-19 pandemic and infection prevention and control measures accelerated work by the NHS to enable and stimulate the use of online consultation (OC) systems across all practices for improved access to primary care. We aimed to explore general practice coding activity associated with the use of OC systems in terms of trends, COVID-19 effect, variation, and quality. With the approval of NHS England, the OpenSAFELY platform was used to query and analyze the in situ electronic health records of suppliers The Phoenix Partnership (TPP) and Egton Medical Information Systems, covering >53 million patients in >6400 practices, mainly in 2019-2020. Systematized Medical Nomenclature for Medicine-Clinical Terminology (SNOMED-CT) codes relevant to OC systems and written OCs were identified including eConsultation. Events were described by volumes and population rates, practice coverage, and trends before and after the COVID-19 pandemic. Variation was characterized among practices, by sociodemographics, and by clinical history of long-term conditions. Overall, 3,550,762 relevant coding events were found in practices using TPP, with the code eConsultation detected in 84.56% (2157/2551) of practices. Activity related to digital forms of interaction increased rapidly from March 2020, the onset of the pandemic; namely, in the second half of 2020, >9 monthly eConsultation coding events per 1000 registered population were registered compared to <1 a year prior. However, we found large variations among regions and practices: December 2020 saw the median practice have 0.9 coded instances per 1000 population compared to at least 36 for the highest decile of practices. On sociodemographics, the TPP cohort with OC instances, when compared (univariate analysis) to the cohort with general practitioner consultations, was more predominantly female (661,235/1,087,919, 60.78% vs 9,172,833/17,166,765, 53.43%), aged 18 to 40 years (349,162/1,080,589, 32.31% vs 4,295,711/17,000,942, 25.27%), White (730,389/1,087,919, 67.14% vs 10,887,858/17,166,765, 63.42%), and less deprived (167,889/1,068,887, 15.71% vs 3,376,403/16,867,074, 20.02%). Looking at the eConsultation code through multivariate analysis, it was more commonly recorded among patients with a history of asthma (adjusted odds ratio [aOR] 1.131, 95% CI 1.124-1.137), depression (aOR 1.144, 95% CI 1.138-1.151), or atrial fibrillation (aOR 1.119, 95% CI 1.099-1.139) when compared to other patients with general practitioner consultations, adjusted for long-term conditions, age, and gender. We successfully queried general practice coding activity relevant to the use of OC systems, showing increased adoption and key areas of variation during the pandemic at both sociodemographic and clinical levels. The work can be expanded to support monitoring of coding quality and underlying activity. This study suggests that large-scale impact evaluation studies can be implemented within the OpenSAFELY platform, namely looking at patient outcomes.