The role of Type I interferons in the pathogenesis of foot-and-mouth disease virus in cattle: a mathematical modelling analysis

Type I interferons (IFN) are the first line of immune response against infection. In this study, we explore the interaction between Type I IFN and foot-and-mouth disease virus (FMDV), focusing on the effect of this interaction on epithelial cell death. While several mathematical models have explored the interaction between interferon and viruses at a systemic level, with most of the work undertaken on influenza and hepatitis C, these cannot investigate why a virus such as FMDV causes extensive cell death in some epithelial tissues leading to the development of lesions, while other infected epithelial tissues exhibit negligible cell death. Our study shows how a model that includes epithelial tissue structure can explain the development of lesions in some tissues and their absence in others. Furthermore, we show how the site of viral entry in an epithelial tissue, the viral replication rate, IFN production, suppression of viral replication by IFN and IFN release by live cells, all have a major impact on results

Cost-effectiveness analysis of maternal immunisation against group B Streptococcus (GBS) disease: A modelling study

Background There is a considerable global burden of invasive group B streptococcal (GBS) disease. Vaccines are being developed for use in pregnant women to offer protection to neonates. Objective To estimate the potential impact and cost-effectiveness of maternal immunisation against neonatal and maternal invasive GBS disease in the UK. Methods We developed a decision-tree model encompassing GBS-related events in infants and mothers, following a birth cohort with a time horizon equivalent to average life expectancy (81 years). We parameterised the model using contemporary data from disease surveillance and outcomes in GBS survivors. Costs were taken from NHS sources and research studies. Maternal immunisation in combination with risk-based intrapartum antibiotic prophylaxis (IAP) was compared to the current standard practice of risk-based IAP alone from an NHS and Personal Social Services (health-provider) perspective. We estimated the cases averted and cost per QALY gained through vaccination. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis were performed. Results An effective maternal immunisation programme could substantially reduce the burden of GBS disease. The deterministic analysis estimated the threshold cost-effective price for a GBS vaccine to be £54 per dose at £20,000/QALY (£71 per dose at £30,000/QALY). Results were most sensitive to assumptions on disease incidence, sequelae rate and vaccine efficacy. Probabilistic analysis showed 90.66% of iterations fell under the £30,000 threshold at a vaccine price of £55. Inclusion of modest prevention of stillbirths and/or, preterm births, carer health impacts, maternal GBS deaths and 1.5% discounting improved cost-effectiveness compared to the base case. Lowering vaccine strain coverage made the vaccine less cost-effective. A key limitation is that the properties of the final GBS vaccine are unknown. Conclusions Maternal GBS immunisation is expected to be cost-effective, even at a relatively high vaccine price

Potential cost-effectiveness of a maternal Group B streptococcal vaccine in The Gambia

Objective To estimate neonatal health benefits and healthcare provider costs of a theoretical Group B streptococcal (GBS) hexavalent maternal vaccination programme in The Gambia, a low-income setting in West Africa. Methods A static decision analytic cost-effectiveness model was developed from the healthcare provider perspective. Demographic data and acute care costs were available from studies in The Gambia undertaken in 2012–2015. Further model parameters were taken from United Nations and World Health Organisation sources, supplemented by data from a global systematic review of GBS and literature searches. As vaccine efficacy is not known, we simulated vaccine efficacy estimates of 50–90%. Costs are reported in US dollars. Cost-effectiveness thresholds of one (US$473, very cost effective) and three (US$1420, cost effective) times Gambian GDP were used. Results Vaccination with a hexavalent vaccine would avert 24 GBS disease cases (55%) and 768 disability adjusted life years compared to current standard of care (no interventions to prevent GBS disease). At vaccine efficacy of 70%, the programme is cost-effective at a maximum vaccine price per dose of 12 US$(2016 US$), and very cost-effective at a maximum of $3/dose. The total costs of vaccination at$12 is $1,056,962 for one annual cohort of Gambian pregnant women. One-way sensitivity analysis showed that GBS incidence was the most influential parameter on the cost effectiveness ratio. Conclusion The introduction of a hexavalent vaccine would considerably reduce the current burden of GBS disease in The Gambia but to be cost-effective, the vaccine price per dose would need to be$12/dose or less

A study protocol for a randomised feasibility study Comparing Urolift and Standard Transurethral resection of prostate Ahead of Radiotherapy in men with urinary symptoms secondary to prostate enlargement in Southwest London and North Cumbria (COSTAR)

Introduction Patients undergoing prostate radiotherapy with an enlarged prostate can have short and long term urinary complications. Currently, Transurethral resection of the prostate (TURP) is the mainstay surgical intervention for men with urinary symptoms due to an enlarged prostate prior to radiotherapy. UroLift (NeoTract Inc., Pleasanton, CA USA) is a recent minimally invasive alternative, widely used in benign disease but is untested in men with prostate cancer. Methods and Analysis A multi-centre, two-arm study designed in collaboration with a Patient Reference Group to assess the feasibility of randomising men with prostate cancer and co-existing urinary symptoms due to prostate enlargement to TURP or UroLift ahead of radiotherapy. 45 patients will be enrolled and randomised (1:1) using a computer-generated programme to TURP or UroLift. Recruitment and retention will be assessed over a 12-month period. Information on clinical outcomes, Adverse Events, and costs will be collected. Clinical outcomes and Patient Reported Outcome Measures (PROMs) will be measured at baseline, six-weeks post-intervention and three months following radiotherapy. A further 12 in-depth interviews will be conducted with a subset of patients to assess acceptability using the Theoretical Framework of Acceptability. Descriptive analysis on all outcomes will be performed using Stata (StataCorp 2021). Ethics and Dissemination The trial has been approved by the Research Ethics Committee (REC) NHS Health Research Authority (HRA) and Health and Care Research Wales (HCRW). The results will be published in peer-reviewed journals, presented at national meetings and disseminated to patients via social media, charity and hospital websites

Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-analyses.

BACKGROUND: Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease. METHODS: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis. RESULTS: We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%-38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%-22%) with moderate to severe NDI. CONCLUSIONS: GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities

Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management & Resource Implications

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015-31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade 2+ ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3-2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days-19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients

Data for: Cost-Effectiveness Analysis of Maternal Immunisation Against Group B Streptococcus (GBS) Disease: a Modelling Study.

Deterministic and probabilistic model code developed by Kyriaki Giorgakoudi for investigating the cost-effectiveness of group B streptococcus vaccination.Methodology described in paper:&apos;Cost-Effectiveness Analysis of Maternal Immunisation Against Group B Streptococcus (GBS) Disease: a Modelling Study&apos;[email protected] Institute of Environment, Health and Societies, Brunel University London, London, U

Data for: Cost-Effectiveness Analysis of Maternal Immunisation Against Group B Streptococcus (GBS) Disease: a Modelling Study.

Deterministic and probabilistic model code developed by Kyriaki Giorgakoudi for investigating the cost-effectiveness of group B streptococcus vaccination.Methodology described in paper:&apos;Cost-Effectiveness Analysis of Maternal Immunisation Against Group B Streptococcus (GBS) Disease: a Modelling Study&apos;[email protected] Institute of Environment, Health and Societies, Brunel University London, London, UKTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV