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BackgroundTo identify risk factors associated with increased risk of hospitalisation, intensive care unit (ICU) admission and mortality in inner North East London (NEL) during the first UK COVID-19 wave.MethodsMultivariate logistic regression analysis on linked primary and secondary care data from people aged 16 or older with confirmed COVID-19 infection between 01/02/2020-30/06/2020 determined odds ratios (OR), 95% confidence intervals (CI) and p-values for the association between demographic, deprivation and clinical factors with COVID-19 hospitalisation, ICU admission and mortality.ResultsOver the study period 1,781 people were diagnosed with COVID-19, of whom 1,195 (67%) were hospitalised, 152 (9%) admitted to ICU and 400 (23%) died. Results confirm previously identified risk factors: being male, or of Black or Asian ethnicity, or aged over 50. Obesity, type 2 diabetes and chronic kidney disease (CKD) increased the risk of hospitalisation. Obesity increased the risk of being admitted to ICU. Underlying CKD, stroke and dementia in-creased the risk of death. Having learning disabilities was strongly associated with increased risk of death (OR=4.75, 95%CI=(1.91,11.84), p=0.001). Having three or four co-morbidities increased the risk of hospitalisation (OR=2.34,95%CI=(1.55,3.54),pConclusionsWe confirm that age, sex, ethnicity, obesity, CKD and diabetes are important determinants of risk of COVID-19 hospitalisation or death. For the first time, we also identify people with learning disabilities and multi-morbidity as additional patient cohorts that need to be actively protected during COVID-19 waves.

Background and aim Mortality of alcohol-related liver disease (ArLD) is increasing, and liver fibrosis stage is the best mortality predictor. Non-invasive tests (NITs) are increasingly used to detect fibrosis, but their value as prognostic tests in chronic liver disease, and in particular in ArLD, is less well recognized. We aimed to describe the prognostic performance of four widely used NITs (Fibrosis 4 test [FIB4], Enhanced Liver Fibrosis [ELF] test, FibroScan, and FibroTest) in ArLD. Methods Applying systematic review methodology, we searched four databases from inception to May 2020. Inclusion/exclusion criteria were applied to search using Medical Subject Heading terms and keywords. The first and second reviewers independently screened results, extracted data, and performed risk-of-bias assessment using Quality in Prognosis Studies tool. Results Searches produced 25 088 articles. After initial screening, 1020 articles were reviewed independently by both reviewers. Eleven articles remained after screening for eligibility: one on ELF, four on FibroScan, four on FIB4, one on FIB4 + FibroScan, and one on FibroTest + FIB4. Area under the receiver operating characteristic curves for outcome prediction ranged from 0.65 to 0.76 for FibroScan, 0.64 to 0.83 for FIB4, 0.69 to 0.79 for FibroTest, and 0.72 to 0.85 for ELF. Studies scored low-moderate risk of bias for most domains but high risk in confounding/statistical reporting domains. The results were heterogeneous for outcomes and reporting, making pooling of data unfeasible. Conclusions This systematic review returned 11 papers, six of which were conference abstracts and one unpublished manuscript. While the heterogeneity of studies precluded direct comparisons of NITs, each NIT performed well in individual studies in predicting prognosis in ArLD (area under the receiver operating characteristic curves >0.7 in each NIT category) and may add value to prognostication in clinical practice.

Background The lockdown periods to curb COVID-19 transmission have made it harder for survivors of domestic violence and abuse (DVA) to disclose abuse and access support services. Our study describes the impact of the first COVID-19 wave and the associated national lockdown in England and Wales on the referrals from general practice to the Identification and Referral to Improve Safety (IRIS) DVA programme. We compare this to the change in referrals in the same months in the previous year, during the school holidays in the 3 years preceding the pandemic and the period just after the first COVID-19 wave. School holiday periods were chosen as a comparator, since families, including the perpetrator, are together, affecting access to services. Methods We used anonymised data on daily referrals received by the IRIS DVA service in 33 areas from general practices over the period April 2017–September 2020. Interrupted-time series and non-linear regression were used to quantify the impact of the first national lockdown in March–June 2020 comparing analogous months the year before, and the impact of school holidays (01/04/2017–30/09/2020) on number of referrals, reporting Incidence Rate Ratio (IRR), 95% confidence intervals and p-values. Results The first national lockdown in 2020 led to reduced number of referrals to DVA services (27%, 95%CI = (21,34%)) compared to the period before and after, and 19% fewer referrals compared to the same period in the year before. A reduction in the number of referrals was also evident during the school holidays with the highest reduction in referrals during the winter 2019 pre-pandemic school holiday (44%, 95%CI = (32,54%)) followed by the effect from the summer of 2020 school holidays (20%, 95%CI = (10,30%)). There was also a smaller reduction (13–15%) in referrals during the longer summer holidays 2017–2019; and some reduction (5–16%) during the shorter spring holidays 2017–2019. Conclusions We show that the COVID-19 lockdown in 2020 led to decline in referrals to DVA services. Our findings suggest an association between decline in referrals to DVA services for women experiencing DVA and prolonged periods of systemic closure proxied here by both the first COVID-19 national lockdown or school holidays. This highlights the need for future planning to provide adequate access and support for people experiencing DVA during future national lockdowns and during the school holidays.

BACKGROUND: As lockdown measures to slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begin to ease in the UK, it is important to assess the impact of any changes in policy, including school reopening and broader relaxation of physical distancing measures. We aimed to use an individual-based model to predict the impact of two possible strategies for reopening schools to all students in the UK from September, 2020, in combination with different assumptions about relaxation of physical distancing measures and the scale-up of testing.METHODS: In this modelling study, we used Covasim, a stochastic individual-based model for transmission of SARS-CoV-2, calibrated to the UK epidemic. The model describes individuals' contact networks stratified into household, school, workplace, and community layers, and uses demographic and epidemiological data from the UK. We simulated six different scenarios, representing the combination of two school reopening strategies (full time and a part-time rota system with 50% of students attending school on alternate weeks) and three testing scenarios (68% contact tracing with no scale-up in testing, 68% contact tracing with sufficient testing to avoid a second COVID-19 wave, and 40% contact tracing with sufficient testing to avoid a second COVID-19 wave). We estimated the number of new infections, cases, and deaths, as well as the effective reproduction number (R) under different strategies. In a sensitivity analysis to account for uncertainties within the stochastic simulation, we also simulated infectiousness of children and young adults aged younger than 20 years at 50% relative to older ages (20 years and older).FINDINGS: With increased levels of testing (between 59% and 87% of symptomatic people tested at some point during an active SARS-CoV-2 infection, depending on the scenario), and effective contact tracing and isolation, an epidemic rebound might be prevented. Assuming 68% of contacts could be traced, we estimate that 75% of individuals with symptomatic infection would need to be tested and positive cases isolated if schools return full-time in September, or 65% if a part-time rota system were used. If only 40% of contacts could be traced, these figures would increase to 87% and 75%, respectively. However, without these levels of testing and contact tracing, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a second wave that would peak in December, 2020, if schools open full-time in September, and in February, 2021, if a part-time rota system were adopted. In either case, the second wave would result in R rising above 1 and a resulting second wave of infections 2·0-2·3 times the size of the original COVID-19 wave. When infectiousness of children and young adults was varied from 100% to 50% of that of older ages, we still found that a comprehensive and effective test-trace-isolate strategy would be required to avoid a second COVID-19 wave.INTERPRETATION: To prevent a second COVID-19 wave, relaxation of physical distancing, including reopening of schools, in the UK must be accompanied by large-scale, population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of diagnosed individuals.FUNDING: None.

ObjectivesWe explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria.DesignProspective cohort study.SettingA single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein.ParticipantsAll 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020.InterventionNasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR).Outcome measuresWe compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present.ResultsTwenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1–4) among early acute, 4.4 days (1–7) among late acute and 8 days (2–12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified.ConclusionsRT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.

Background: Testing for COVID-19 with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) may result in delayed detection of disease. Antigen detection via lateral flow testing (LFT) is faster and amenable to population-wide testing strategies. Our study assesses the diagnostic accuracy of LFT compared to RT-PCR on the same primarycare patients in Austria. Methods: Patients with mild to moderate flu-like symptoms attending a general practice network in an Austrian district (October 22 to November 30, 2020) received clinical assessment including LFT. All suspected COVID-19 cases obtained additional RT-PCR and were divided into two groups: Group 1 (true reactive): suspected cases with reactive LFT and positive RT-PCR; and Group 2 (false non-reactive): suspected cases with a non-reactive LFT but positive RT-PCR. Findings: Of the 2,562 symptomatic patients, 1,037 were suspected of COVID-19 and 826 (79.7%) patients tested RT-PCR positive. Among patients with positive RT-PCR, 788/826 tested LFT reactive (Group 1) and 38 (4.6%) non-reactive (Group 2). Overall sensitivity was 95.4% (95%CI: [94%,96.8%]), specificity 89.1% (95%CI: [86.3%, 91.9%]), positive predictive value 97.3% (95%CI:[95.9%, 98.7%]) and negative predictive value 82.5% (95%CI:[79.8%, 85.2%]). Reactive LFT and positive RT-PCR were positively correlated (r = 0.968,95CI=[0.952,0.985] and κ=0.823, 95%CI=[0.773,0.866]). Reactive LFT was negatively correlated with Ct-value (r = -0.2999,p

COVID-19 in the UK has had a profound impact on population health and other socially important outcomes, including on education and the economy. Although a range of evidence has guided policy, epidemiological models have been central. It is less clear whether models to support decision making have sought to integrate COVID-19 epidemiology with a consideration of broader health, wellbeing and economic implications. We report on a rapid review of studies seeking to integrate epidemiological and economic modelling to assess the impacts of alternative policies. Overall, our results suggest that few studies have explored broader impacts of different COVID-19 policies in the UK. Three studies looked only at health, capturing impacts on individuals with and without COVID-19, with various methods used to model the latter. Four models considered health and wider impacts on individuals’ economic outcomes, such as wages. However, these models made no attempt to consider the dynamic impacts on economic outcomes of others and the wider economy. The most complex analyses sought to link epidemiological and dynamic economic models. Studies compared a wide range of policies, although most were defined in general terms with minimal consideration of their granular specifications. There was minimal exploration of uncertainty, with no consideration in half the studies. Selecting appropriate models to inform decisions requires careful thought of factors relevant to the decision options under consideration such as the outcomes of interest, sectors likely to be impacted and causal pathways. In summary, better linking epidemiological and economic modelling would help to inform COVID-19 policy. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01045-2.

ObjectivesTwenty per cent of people with alcohol use disorders develop advanced fibrosis and warrant referral to secondary care. Improving outcomes in alcohol-related liver disease (ArLD) relies on its earlier detection in primary care with non-invasive tests (NIT). We aimed to determine the proportion of alcohol-related referrals who were diagnosed with advanced fibrosis in secondary care, the prevalence of both alcohol and fatty liver disease (‘BAFLD’) and the potential impact of NIT on referral stratification.Design/settingRetrospective analysis of all general practitioner-referrals with suspected ArLD/non-alcoholic fatty liver disease (NAFLD) to a UK hepatology-centre between January 2015 and January 2018.ParticipantsOf 2944 new referrals, 762 (mean age 55.5±13.53 years) met inclusion criteria: 531 NAFLD and 231 ArLD, of which 147 (64%) could be reclassified as ‘BAFLD’.Primary outcome measureProportion of referrals with suspected ArLD/NAFLD with advanced fibrosis as assessed by tertiary centre hepatologists using combinations of FibroScan, imaging, examination and blood tests and liver histology, where indicated.Secondary outcome measuresIncluded impact of body mass index/alcohol consumption on the odds of a diagnosis of advanced fibrosis, and performance of NIT in predicting advanced fibrosis in planned post-hoc analysis of referrals.ResultsAmong ArLD referrals 147/229 (64.2%) had no evidence of advanced fibrosis and were judged ‘unnecessary’. Advanced fibrosis was observed in men drinking ≥50 units per week (U/w) (OR 2.74, 95% CI 1.51 to 5, p=0.001) and ≥35 U/w in women (OR 5.11, 95% CI 1.31 to 20.03, p=0.019). Drinking >14 U/w doubled the likelihood of advanced fibrosis in overweight/obesity (OR 2.11; 95% CI 1.44 to 3.09; pConclusionsThe majority of referrals with suspected ArLD were deemed unnecessary. NIT could improve identification of liver damage in ArLD, BAFLD and NAFLD in primary care. Anecdotal thresholds for harmful drinking (35 U/w in women and 50 U/w in men) were validated. The impact of alcohol on NAFLD highlights the importance of multi-causality in chronic liver disease.

Background T1‐weighted dynamic contrast‐enhanced (DCE) perfusion magnetic resonance imaging (MRI) has been broadly utilized in the evaluation of brain tumors. We aimed at assessing the diagnostic accuracy of DCE‐MRI in discriminating between low‐grade gliomas (LGGs) and high‐grade gliomas (HGGs), between tumor recurrence and treatment‐related changes, and between primary central nervous system lymphomas (PCNSLs) and HGGs. Methods We performed this study based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis of Diagnostic Test Accuracy Studies criteria. We systematically surveyed studies evaluating the diagnostic accuracy of DCE‐MRI for the aforementioned entities. Meta‐analysis was conducted with the use of a random effects model. Results Twenty‐seven studies were included after screening of 2945 possible entries. We categorized the eligible studies into three groups: those utilizing DCE‐MRI to differentiate between HGGs and LGGs (14 studies, 546 patients), between recurrence and treatment‐related changes (9 studies, 298 patients) and between PCNSLs and HGGs (5 studies, 224 patients). The pooled sensitivity, specificity, and area under the curve for differentiating HGGs from LGGs were 0.93, 0.90, and 0.96, for differentiating tumor relapse from treatment‐related changes were 0.88, 0.86, and 0.89, and for differentiating PCNSLs from HGGs were 0.78, 0.81, and 0.86, respectively. Conclusions Dynamic contrast‐enhanced‐Magnetic resonance imaging is a promising noninvasive imaging method that has moderate or high accuracy in stratifying gliomas. DCE‐MRI shows high diagnostic accuracy in discriminating between HGGs and their low‐grade counterparts, and moderate diagnostic accuracy in discriminating recurrent lesions and treatment‐related changes as well as PCNSLs and HGGs., Dynamic contrast‐enhanced‐Magnetic resonance imaging has high diagnostic accuracy in grading gliomas and moderate accuracy in surveillance of high‐grade gliomas and differentiation from primary central nervous system lymphomas. DCE‐MRI is a promising noninvasive imaging technique in diagnosing different types of brain tumors.

Background The implementation of lockdowns in the UK during the COVID-19 pandemic resulted in a system switch to remote primary care consulting at the same time as the incidence of domestic violence and abuse (DVA) increased. Lockdown-specific barriers to disclosure of DVA reduced the opportunity for DVA detection and referral. The PRECODE (PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic) study will comprise quantitative analysis of the impact of the pandemic on referrals from IRIS (Identification and Referral to Improve Safety) trained general practices to DVA agencies in the UK and qualitative analysis of the experiences of clinicians responding to patients affected by DVA and adaptations they have made transitioning to remote DVA training and patient support. Methods/Design Using a rapid mixed method design, PRECODE will explore and explain the dynamics of DVA referrals and support before and during the pandemic on a national scale using qualitative data and over four years of referrals time series data. We will undertake interrupted-time series and non-linear regression analysis, including sensitivity analyses, on time series of referrals to DVA services from routinely collected data to evaluate the impact of the pandemic and associated lockdowns on referrals to the IRIS Programme, and analyse key determinants associated with changes in referrals. We will also conduct an interview- and observation-based qualitative study to understand the variation, relevance and feasibility of primary care responses to DVA before and during the pandemic and its aftermath. The triangulation of quantitative and qualitative findings using rapid analysis and synthesis will enable the articulation of multiscale trends in primary care responses to DVA and complex mechanisms by which these responses have changed during the pandemic. Discussion Our findings will inform the implementation of remote primary care and DVA service responses as services re-configure. Understanding the adaptation of clinical and service responses to DVA during the pandemic is crucial for the development of evidence-based, effective remote support and referral beyond the pandemic. Trial registration PRECODE is an observational epidemiologic study, not an intervention evaluation or trial. We will not be reporting results of an intervention on human participants.

Background The COVID-19 pandemic and the associated lockdowns have caused significant disruptions across society, including changes in the number of emergency department (ED) visits. This study aims to investigate the impact of three pre-COVID-19 interventions and of the COVID-19 UK-epidemic and the first UK national lockdown on overcrowding within University College London Hospital Emergency Department (UCLH ED). The three interventions: target the influx of patients at ED (A), reduce the pressure on in-patients’ beds (B) and improve ED processes to improve the flow of patents out from ED (C). Methods We collected overcrowding metrics (daily attendances, the proportion of people leaving within 4 h of arrival (four-hours target) and the reduction in overall waiting time) during 01/04/2017–31/05/2020. We then performed three different analyses, considering three different timeframes. The first analysis used data 01/04/2017–31/12–2019 to calculate changes over a period of 6 months before and after the start of interventions A-C. The second and third analyses focused on evaluating the impact of the COVID-19 epidemic, comparing the first 10 months in 2020 and 2019, and of the first national lockdown (23/03/2020–31/05/2020). Results Pre-COVID-19 all interventions led to small reductions in waiting time (17%, p p = 0.322 for B) but also to a small decrease in the number of patients leaving within 4 h of arrival (6.6,7.4,6.2% respectively A-C,p In presence of the COVID-19 pandemic, attendance and waiting time were reduced (40% and 8%; p p p p Conclusions The mixed results pre-COVID-19 (significant improvements in waiting time with some interventions but not improvement in the four-hours target), may be due to indirect impacts of these interventions, where increasing pressure on one part of the ED system affected other parts. This underlines the need for multifaceted interventions and a system-wide approach to improve the pathway of flow through the ED system is necessary. During 2020 and in presence of the COVID-19 epidemic, a shift in public behaviour with anxiety over attending hospitals and higher use of virtual consultations, led to notable drop in UCLH ED attendance and consequential curbing of overcrowding. Importantly, once the lockdown was lifted, although there was an increase in arrivals at UCLH ED, overcrowding metrics were reduced. Thus, the combination of shifted public behaviour and the restructuring changes during COVID-19 epidemic, maybe be able to curb future ED overcrowding, but longer timeframe analysis is required to confirm this.

Background: Testing for COVID-19 with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) may result in delayed detection of disease. Antigen detection via lateral flow testing (LFT) is faster and amenable to mass testing strategies. Our study assesses the diagnostic accuracy of LFT compared to RT-PCR on the same primary-care patients in Austria. Methods: Prospective dataset of 2,562 patients presenting with mild to moderate flu-like symptoms to 20 practices in the district of Liezen, Austria, between October 22 and November 30, 2020. Symptomatic patients received clinical assessment, including both tests, and were split in two groups: Group 1 (true reactive): Suspected COVID-19 cases with a reactive LFT, who tested RT-PCR positive; and Group 2 (false non-reactive): Suspected COVID-19 cases with a non-reactive LFT, who tested RT-PCR positive. We report the number of cases detected with each test, evaluate the correlation of RT-PCR positivity with reactive LFT and report clinical sensitivity and specificity of LFT, positive predictive value (PPV), negative predictive value (NPV), and pre-test duration of symptoms and RT-PCR cycle threshold (Ct) value across groups. Regression analysis quantifies the association between reactive LFT and symptom duration and Ct value respectively. Findings: Of the 2,562 symptomatic patients, 1,037 were suspected of COVID-19: 826 (79.7%) tested RT-PCR positive 201 (19.8%) RT-PCR negative and 10 (0.5%) with inconclusive RT-PCR. Among patients with positive RT-PCR, 788/826 tested LFT reactive (Group 1) and 38 (4.6%) non-reactive (Group 2); Of those with negative RT-PCR, 179/201 tested LFT non-reactive and 22/201 reactive. Clinical sensitivity (95.4%) and specificity (89.1%), and PPV (97.3%) and NPV (82.5%) were high. Test outcomes of both LFT and RT-PCR were positively correlated (r=0.968,95CI=[0.952,0.985]). Reactive LFT was negatively correlated with Ct value (r=0.2999,p

Background With a suite of promising new RSV prophylactics on the horizon, including long-acting monoclonal antibodies and new vaccines, it is likely that one or more of these will replace the current monoclonal Palivizumab programme. However, choosing the optimal intervention programme will require balancing the costs of the programmes with the health benefits accrued. Methods To compare the next generation of RSV prophylactics, we integrated a novel transmission model with an economic analysis. We estimated key epidemiological parameters by calibrating the model to 7 years of historical epidemiological data using a Bayesian approach. We determined the cost-effective and affordable maximum purchase price for a comprehensive suite of intervention programmes. Findings Our transmission model suggests that maternal protection of infants is seasonal, with 38–62% of infants born with protection against RSV. Our economic analysis found that to cost-effectively and affordably replace the current monoclonal antibody Palivizumab programme with long-acting monoclonal antibodies, the purchase price per dose would have to be less than around £4350 but dropping to £200 for vaccinated heightened risk infants or £90 for all infants. A seasonal maternal vaccine would have to be priced less than £85 to be cost-effective and affordable. While vaccinating pre-school and school-age children is likely not cost-effective relative to elderly vaccination programmes, vaccinating the elderly is not likely to be affordable. Conversely, vaccinating infants at 2 months seasonally would be cost-effective and affordable if priced less than £80. Conclusions In a setting with seasonal RSV epidemiology, maternal protection conferred to newborns is also seasonal, an assumption not previously incorporated in transmission models of RSV. For a country with seasonal RSV dynamics like England, seasonal programmes rather than year-round intervention programmes are always optimal.

Background and aims Alcohol use disorders (AUD) cause 7.2% of UK hospital admissions/year. Most are not managed by hepatologists and liver disease may be missed. We used the Enhanced Liver Fibrosis (ELF) test to investigate prevalence and associations of occult advanced liver fibrosis in AUD patients not known to have liver fibrosis. Methods Liver fibrosis was assessed using ELF in prospective patients referred to the Royal Free Hospital Alcohol Specialist Nurse (November 2018–December 2019). Known cases of liver disease were excluded. Patient demographics, blood tests, imaging data and alcohol histories recorded. Advanced fibrosis was categorised as ELF ≥ 10.5. Results The study included 99 patients (69% male, mean age 53.1 ± 14.4) with median alcohol intake 140 units/week (IQR 80.9–280), and a mean duration of harmful drinking of 15 years (IQR 10–27.5). The commonest reason for admission was symptomatic alcohol withdrawal (36%). The median ELF score was 9.62, range 6.87–13.78. An ELF score ≥ 10.5 was recorded in 28/99 (29%) patients, of whom 28.6% had normal liver tests. Within previous 5-years, 76% had attended A&E without assessment of liver disease. The ELF score was not associated with recent alcohol intake (p = 0.081), or inflammation (p = 0.574). Conclusion Over a quarter of patients with AUD had previously undetected advanced liver fibrosis assessed by ELF testing. ELF was not associated with liver inflammation or recent alcohol intake. The majority had recent missed opportunities for investigating liver disease. We recommend clinicians use non-invasive tests to assess liver fibrosis in patients admitted to hospital with AUD.

BackgroundDelay in COVID-19 detection has led to a major pandemic. We report rapid early detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR), comparing it to the serostatus of convalescent infection, at an Austrian National Sentinel Surveillance Practice in an isolated ski-resort serving a population of 22,829 people.MethodsRetrospective dataset of all 73 patients presenting with mild to moderate flu-like symptoms to a sentinel practice in the ski-resort of Schladming-Dachstein, Austria, between 24 February and 03 April, 2020. We split the outbreak in two halves, by dividing the period from the first to the last case by two, to characterise the following three cohorts of patients with confirmed infection: people with reactive RT-PCR presenting during the first half (early acute infection) vs. those presenting in the second half (late acute), and people with non-reactive RT-PCR (late convalescent). For each cohort we report the number of cases detected, the accuracy of RT-PCR and the duration of symptoms. We also report multivariate regression of 15 clinical symptoms as covariates, comparing all people with convalescent infection to those with acute infection.FindingsAll 73 patients had SARS-CoV-2 RT-PCR testing. 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. RT-PCR sensitivity was high (100%) among acute presenters, but dropped to 50% in the second half of the outbreak; specificity was 100%. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, and 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent presenters respectively. Convalescent infection was only associated with loss of taste (ORs=6.02;p=0.047). Acute infection was associated with loss of taste (OR=571.72;p=0.029), nausea and vomiting (OR=370.11;p=0.018), breathlessness (OR=134.46;p=0.049), and myalgia (OR=121.82;p=0.032); but not loss of smell, fever or cough.InterpretationRT-PCR rapidly and reliably detects early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. RT-PCR testing in primary care should be prioritised for effective COVID-19 prevention and control.Research in ContextEvidence before this studyA comprehensive and effective test-trace-isolate (TTI) strategy is necessary to keep track of current and future COVID-19 infection in the UK and avoid a secondary wave later this year, as society reopens. As part of a wider TTI strategy, it is important to assess the feasibility of COVID-19 testing in primary care. We searched PubMed for implementation of SARS-CoV-2 testing in primary care using the following search terms: (“SARS-CoV-2” OR “COVID-19”) AND “testing” AND (“primary care” OR “general practice”). We did not find any studies that met these criteria.Added value of this studyTo our knowledge, our study provides first evidence that extension of a National Influenza Surveillance Programme to include SARS-CoV-2 RT-PCR testing in primary care leads to viral detection among patients presenting with mild to moderate flu-like illness during a local outbreak of COVID-19. We show that the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR), the technique to detect viral RNA, is high (100%) in the initial phase of the outbreak and among patients who were acutely unwell. Acute infection was associated with multiply symptoms: loss of taste, nausea and vomiting, breathlessness, myalgia and sore throat; but not loss of smell, fever or cough. We also show high correlation between reactive RT-PCR and seropositivity.Implications of all available evidenceOur findings suggest that RT-PCR can rapidly and reliably detect early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. Furthermore RT-PCR testing in primary care can effectively detect new COVID-19 clusters in the community and should be included in any strategy for prevention and control of the disease.

Background Domestic violence and abuse (DVA) is experienced by about 1/3 of women globally and remains a major health concern worldwide. IRIS (Identification and Referral to Improve Safety of women affected by DVA) is a complex, system-level, training and support programme, designed to improve the primary healthcare response to DVA. Following a successful trial in England, since 2011 IRIS has been implemented in eleven London boroughs. In two boroughs the service was disrupted temporarily. This study evaluates the impact of that service disruption. Methods We used anonymised data on daily referrals received by DVA service providers from general practices in two IRIS implementation boroughs that had service disruption for a period of time (six and three months). In line with previous work we refer to these as boroughs B and C. The primary outcome was the number of daily referrals received by the DVA service provider across each borough over 48 months (March 2013–April 2017) in borough B and 42 months (October 2013–April 2017) in borough C. The data were analysed using interrupted-time series, non-linear regression with sensitivity analyses exploring different regression models. Incidence Rate Ratio (IRR), 95% confidence intervals and p-values associated with the disruption were reported for each borough. Results A mixed-effects negative binomial regression was the best fit model to the data. In borough B, the disruption, lasted for about six months, reducing the referral rate significantly (p = 0.006) by about 70% (95%CI = (23,87%)). In borough C, the three-month service disruption, also significantly (p = 0.005), reduced the referral rate by about 49% (95% CI = (18,68%)). Conclusions Disrupting the IRIS service substantially reduced the rate of referrals to DVA service providers. Our findings are evidence in favour of continuous funding and staffing of IRIS as a system level programme.

Objective: Diffusion tensor imaging (DTI) is a useful neuroimaging technique for surgical planning in adult patients. However, no systematic review has been conducted to determine its utility for pre-operative analysis and planning of Pediatric Epilepsy surgery. We sought to determine the benefit of pre-operative DTI in predicting and improving neurological functional outcome after epilepsy surgery in children with intractable epilepsy. Methods: A systematic review of articles in English using PubMed, EMBASE and Scopus databases, from inception to January 10, 2020 was conducted. All studies that used DTI as either predictor or direct influencer of functional neurological outcome (motor, sensory, language and/or visual) in pediatric epilepsy surgical candidates were included. Data extraction was performed by two blinded reviewers. Risk of bias of each study was determined using the QUADAS 2 Scoring System. Results: 13 studies were included (6 case reports/series, 5 retrospective cohorts, and 2 prospective cohorts) with a total of 229 patients. Seven studies reported motor outcome; three reported motor outcome prediction with a sensitivity and specificity ranging from 80 to 85.7 and 69.6 to 100%, respectively; four studies reported visual outcome. In general, the use of DTI was associated with a high degree of favorable neurological outcomes after epilepsy surgery. Conclusion: Multiple studies show that DTI helps to create a tailored plan that results in improved functional outcome. However, more studies are required in order to fully assess its utility in pediatric patients. This is a desirable field of study because DTI offers a non-invasive technique more suitable for children. Advances in knowledge: This systematic review analyses, exclusively, studies of pediatric patients with drug-resistant epilepsy and provides an update of the evidence regarding the role of DTI, as part of the pre-operative armamentarium, in improving post-surgical neurological sequels and its potential for outcome prediction.

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting., Author summary Tuberculosis (TB) remains a leading global cause of death and morbidity, and 85% of deaths occur in countries where resources for TB care and control are limited. Many countries cannot finance all TB interventions or technologies, which means difficult decisions on what to prioritise and publically finance. Modelling tools can help decision-makers set priorities based on evidence, in a systematic and transparent way. This study presents Optima TB, a tool that estimates which allocations of spending across interventions will most likely maximise specified objectives—such as minimising TB deaths, prevalence and incidence. In partnership with local decision-makers and stakeholders, Optima TB was applied in Belarus. Recommendations from the model findings include focussing investment on outpatient rather than inpatient care and actively finding people with TB (e.g. through contact tracing) rather than mass testing of the population. The recommended reallocations of spending could reduce TB prevalence and deaths by up to 45% and 50%, respectively, by 2035 for the same amount of spending. Key stakeholders were engaged throughout the analysis and findings and uncertainty around the results were clearly communicated with decision-makers. The timeliness of the results helped inform national dialogue on TB care reform, among other key policy discussions.

BackgroundWith a suite of promising new RSV prophylactics on the horizon, including long-acting monoclonal antibodies and new vaccines, it is likely that one or more of these will replace the current monoclonal Palivizumab programme. However, choosing the optimal intervention programme will require balancing the costs of the programmes with the health benefits accrued.MethodsTo compare the next generation of RSV prophylactics, we integrated a novel transmission model with an economic analysis. We estimated key epidemiological parameters by calibrating the model to seven years of historical epidemiological data using a Bayesian approach. We determined the cost-effective and affordable maximum purchase price for a comprehensive suite of intervention programmes.FindingsOur transmission model suggests that maternal protection of infants is seasonal, with 2-14% of infants born with protection against RSV. Our economic analysis found that to cost-effectively and affordably replace the current monoclonal antibody Palivizumab programme with long-acting monoclonal antibodies, the purchase price per dose would have to be less than around £4,350 but dropping to £200 for vaccinated heightened risk infants or £90 for all infants. A seasonal maternal vaccine would have to be priced less than £85 to be cost-effective and affordable. While vaccinating pre-school and school-age children is likely not cost-effective relative to elderly vaccination programmes, vaccinating the elderly is not likely to be affordable. Conversely, vaccinating infants at 2 months seasonally would be cost-effective and affordable if priced less than £80.InterpretationsIn a setting with seasonal RSV epidemiology, maternal protection conferred to newborns is also seasonal, an assumption not previously incorporated in transmission models of RSV. For a country with seasonal RSV dynamics like England, seasonal programmes rather than year-round intervention programmes are always optimal.FundingMedical Research Council and National Institute for Health ResearchRESEARCH IN CONTEXTEvidence before this studyA recent systematic review identified RSV prophylactic candidates currently in clinical trials, including a maternal vaccine (RSV F-nanoparticles vaccine), long-acting monoclonal antibodies aimed at neonates (MEDI8897), and an active adenovirus vector-based vaccine aimed at infants and/or the elderly (ChAd155-RSV). Given the significant observed health burden due to RSV in children, these products, which are mainly aimed at children, are likely to be effective at preventing RSV disease. However, uncertainties surrounding i) the dynamics of maternally-derived protection in neonates, ii) the impact of herd immunity, and iii) the purchasing cost of these prophylactics, means it is not clear if these products are cost-effective. Therefore, evaluating the purchasing price required for these prophylactics to remain cost-effective using a dynamic transmission model, in which the herd immunity is included and the dynamics of maternally-derived immunity is determined by calibrating the model to data, is a public health priority.Added-value of this studyOur study finds that in a setting with seasonal RSV epidemiology, maternal protection conferred to newborns is also seasonal. In addition, our study estimates the maximum purchasing price per course for various potential RSV intervention programmes to be cost-effective in England, assuming a cost-effectiveness threshold of £20,000/QALY as recommended by the National Institute of Clinical Excellence (NICE). We find that to cost-effectively and affordably replace the current monoclonal antibody Palivizumab programme with long-acting monoclonal antibodies, the purchase price per dose would have to be less than around £4,350 but dropping to £200 for vaccinated heightened risk infants or £90 for all infants. A seasonal maternal vaccine would have to be priced less than £85 to be cost-effective and affordable. While vaccinating pre-school and school-age children is likely not cost-effective relative to elderly vaccination programmes, and vaccinating the elderly is not likely to be affordable.Implications of all the available evidenceThe seasonal protection conferred to newborns is consistent with empirical immunological data from maternal cord blood and ecological evidence from hospital records. Further, extending a monoclonal antibody programme would be possible if there is a considerable drop in price and maternal vaccination remains the only realistic vaccination strategy in the UK. With further clinical trials planned for RSV F-nanoparticles vaccine to evaluate its efficacy, and with clinical trial completion dates set at the end of 2021 for the other two prophylactic candidates, the results of this study provide a comprehensive overview of the impact of potential RSV intervention programmes both in the present and in the coming years.

Importance The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior. Objective To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults. Data Sources PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts. Study Selection Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded. Data Extraction and Synthesis PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken. Main Outcomes and Measures Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults. Results A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. Conclusions and Relevance In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.

e14528 Background: Treatment monitoring in patients with High-Grade Glioma (HGG) and identification of disease progression, remains a major challenge in clinical neurooncology. We aimed to develop a support vector machine (SVM) classifier utilising combined longitudinal conventional and Dynamic Susceptibility Contrast (DSC) perfusion MRI to classify between Stable Disease (SD), Pseudoprogression (PsP) and Progressive Disease (PD) in glioma patients under surveillance. Methods: Conventional (269) and perfusion (62) MRI studies of HGG patients acquired between 2012 and 2018 were prospectively analysed. Study participants were separated into two groups: Group I with a single DSC time point (64 participants) and Group II with multiple DSC time points (19 participants). The SVM classifier was trained using all available MRI for each group. Classification accuracy was assessed for the use of features extracted from different feature dataset and time point combinations and compared to the experienced radiologists’ predictions. Results: The study included 64 participants (mean age: 48.5 ± 12.8 yrs [standard deviation], 24 female). SVM classification based on combined perfusion and structural features outperformed standalone datasets across all groups. For the clinically relevant classification step (SD/PSP vs PD), both feature combination as well as the addition of multiple DSC time points, improved classification performance (lowest median error rate: 0.016). The SVM algorithm outperformed radiologists in predicting lesion destiny in both groups. Optimal performance was observed in Group II, in which SVM sensitivity/specificity/accuracy was 100/91.67/94.7% for analysis based on the first time point and 85.71/100/ 94.7% based on multiple time points compared to 60/78/68% and 70/90/84.2% for the respective radiologist classifications. In Group I, the SVM also exceeded radiologist predictions, albeit by a smaller margin and resulted in sensitivity/specificity of 86.49/75.00/81.53% (SVM) compared to 75.7/68.9/73.84% (radiologists). Conclusions: Our results indicate that the addition of multiple longitudinal perfusion time points as well as the combination of structural and perfusion features significantly enhance classification outcome in treatment monitoring of HGGs and machine-learning-assisted diagnosis has potentially superior accuracy than the radiologist's visual evaluation and expertise.

BACKGROUND: In children aged OBJECTIVES: We estimated the age-specific QALY loss due to RSV by developing a regression model which predicts the QALY loss without the use of standardised instruments.METHODS: We conducted a surveillance study which targeted confirmed RSV episodes in children aged FINDINGS: For confirmed RSV cases in children under 5 years of age who sought health care, our model predicted a QALY loss per RSV episode of 3.823 × 10-3 (95% CI 0.492-12.766 × 10-3 ), compared with 3.024 × 10-3 (95% CI 0.329-10.098 × 10-3 ) for under fives who did not seek health care. Quality of life years loss per episode was less for older children and adults, estimated as 1.950 × 10-3 (0.185-9.578 × 10-3 ) and 1.543 × 10-3 (0.136-6.406 × 10-3 ) for those who seek or do not seek health care, respectively.CONCLUSION: Evaluations of potential RSV vaccination programmes should consider their impact across the whole population, not just young child children.

BACKGROUND: Continuous monitoring of cerebral autoregulation might provide novel treatment targets and identify therapeutic windows after acute brain injury. Slow oscillations of cerebral hemodynamics (0.05-0.003 Hz) are visible in multimodal neuromonitoring and may be analyzed to provide novel, surrogate measures of autoregulation. Near-infrared spectroscopy (NIRS) is an optical neuromonitoring technique, which shows promise for widespread clinical applicability because it is noninvasive and easily delivered across a wide range of clinical scenarios. The aim of this study is to identify the relationship between NIRS signal oscillations and multimodal neuromonitoring, examining the utility of near infrared derived indices of cerebrovascular reactivity. METHODS: Twenty-seven sedated, ventilated, brain-injured patients were included in this observational study. Intracranial pressure, transcranial Doppler-derived flow velocity in the middle cerebral artery, and ipsilateral cerebral NIRS variables were continuously monitored. Signals were compared using wavelet measures of phase and coherence to examine the spectral features involved in reactivity index calculations. Established indices of autoregulatory reserve such as the pressure reactivity index (PRx) and mean velocity index (Mx) and the NIRS indices such as total hemoglobin reactivity index (THx) and tissue oxygen reactivity index (TOx) were compared using correlation and Bland-Altman analysis. RESULTS: NIRS indices correlated significantly between PRx and THx (r = 0.63, P < 0.001), PRx and TOx (r = 0.40, P = 0.04), and Mx and TOx (r = 0.61, P = 0.004) but not between Mx and THx (r = 0.26, P = 0.28) and demonstrated wide limits between these variables: PRx and THx (bias, -0.06; 95% limits, -0.44 to 0.32) and Mx and TOx (bias, +0.15; 95% limits, -0.34 to 0.64). Analysis of slow-wave activity throughout the intracranial pressure, transcranial Doppler, and NIRS recordings revealed statistically significant interrelationships, which varied dynamically and were nonsignificant at frequencies

BACKGROUND: In 2013 England and Wales began to fund a live attenuated influenza vaccine programme for individuals aged 2-16 years. Mathematical modelling predicts substantial beneficial herd effects for the entire population as a result of reduced influenza transmission. With a decreased influenza-associated disease burden, existing immunisation programmes might be less cost-effective. The aim of this study was to assess the epidemiological effect and cost-effectiveness of the existing elderly and risk group vaccination programme under the new policy of mass paediatric vaccination in England.METHODS: For this cost-effectiveness analysis, we used a transmission model of seasonal influenza calibrated to 14 seasons of weekly consultation and virology data in England and Wales. We combined this model with an economic evaluation to calculate the incremental cost-effectiveness ratios, measured in cost per quality-adjusted life-years (QALY) gained.FINDINGS: Our results suggest that well timed administration of paediatric vaccination would reduce the number of low-risk elderly influenza cases to a greater extent than would vaccination of the low-risk elderly themselves if the elderly uptake is achieved more slowly. Although high-risk vaccination remains cost-effective, substantial uncertainty exists as to whether low-risk elderly vaccination remains cost-effective, driven by the choice of cost-effectiveness threshold. Under base case assumptions and a cost-effectiveness threshold of £15 000 per QALY, the low-risk elderly seasonal vaccination programme will cease to be cost-effective with a mean incremental cost-effectiveness ratio of £22 000 per QALY and a probability of cost-effectiveness of 20%. However, under a £30 000 per QALY threshold, the programme will remain cost-effective with 83% probability.INTERPRETATION: With the likely move to decreased cost-effectiveness thresholds, reassessment of existing risk group-based vaccine programme cost-effectiveness in the presence of the paediatric vaccination programme is needed.FUNDING: National Institute for Health Research, the Medical Research Council.

Aim and objectives We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas. Methods and materials A review protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P), registered in the international prospective register of systematic reviews, PROSPERO and published. Literature search in 4 databases was performed using the keywords “glioma” and “diffusional kurtosis”.After applying a robust inclusion/exclusion criteria, included articles were independently evaluated according to the QUADAS-2 tool.Data extraction was done in a pre-designed pro forma.Reported sensitivities and specificities were used to construct 2x2 tables and paired forest plots using the Review Manager (RevMan®) software.Random-effect model was pursued using the hierarchical summary receiver operator characteristics. Results Initially, 216 hits were retrieved. Considering duplicates and inclusion criteria; 23 articles were eligible for full-text reading. Ultimately, 19 studies were deemed to be eligible for final inclusion. Quality assessment revealed 9 studies with low risk of bias in the 4 domains. Using a bivariate random-effect model for data synthesis; summary ROC curve showed pooled area under the curve (AUC) of 0.92 and estimated sensitivity of 0.87 (95% CI: 0.78 - 0.92) in high/low grade gliomas’ differentiation.A mean difference in Mean Kurtosis (MK) value between HGG and LGG of 0.22 [95% CI: 0.25 - 0.19] was illustrated (p value = 0.0014) and a moderate degree of heterogeneity (I²= 73.8%). Conclusion DKI shows good diagnostic accuracy in high/low grade gliomas’ differentiation; which might qualify it to be part of the routine clinical practice, however; further evidence is deemed for technique standardization.

2054 Background: Surveillance of High-Grade Gliomas (HGGs) remains a major challenge in clinical neurooncology. Histopathological validation is not an option during the course of disease and imaging surveillance suffers from ambiguous features of both disease progression and treatment related changes. This study aimed to differentiate between Pseudoprogression (PsP) and Progressive Disease (PD) using an artificial intelligence (support vector machine - SVM) classification algorithm. Methods: Two groups of patients with histologically proven HGGs were analysed, a group with a single time point DSC perfusion MRI (45 patients) and a group with multiple time point DSC perfusion MRI (19 patients). Both groups included conventional MRI studies prior and after each perfusion MRI. This study design aimed to replicate decision making in clinical practice including multiple previous studies for each patient. SVM training was performed with all available MRI studies for each group and classification was based on different feature datasets from a single or multiple (subtracted features) time points. Classification accuracy comparisons were performed by calculating prediction error rates for different feature datasets and different time point analyses. Results: Our results indicate that the addition of multiple time point perfusion MRI combined with structural (conventional with gadolinium-enhanced sequences) MRI features results in optimal classification performance (median error rate: 0.016, lowest value dispersion). Subtracted feature datasets improved classification performance, more prominently when the final and first perfusion studies were included in the analysis. On the contrary, in the single time point group analysis, structural feature-based classification performed best (median error rate: 0.012). Conclusions: Validation of our results with a larger patient cohort may have significant clinical importance in optimising imaging surveillance and clinical decision making for patients with HGG.

Raised intracranial pressure (ICP) is a key concern following acute brain injury as it may be associated with cerebral hypoperfusion and poor outcome. In this research we describe a mathematical physiological model designed to interpret cerebral physiology from neuromonitoring: ICP, near-infrared spectroscopy and transcranial Doppler flow velocity. This aims to characterise the complex dynamics of cerebral compliance, cerebral blood volume, cerebral blood flow and their regulation in individual patients. Analysis of data from six brain-injured patients produces cohesive predictions of cerebral biomechanics suggesting reduced cerebral compliance, reduced volume compensation and impaired blood flow autoregulation. Patient-specific physiological modelling has the potential to predict the key biomechanical and haemodynamic changes following brain injury in individual patients, and might be used to inform individualised treatment strategies.

Understanding changes in cerebral oxygenation, haemodynamics and metabolism holds the key to individualised, optimised therapy after acute brain injury. Near-infrared spectroscopy (NIRS) offers the potential for non-invasive, continuous bedside measurement of surrogates for these processes. Interest has grown in applying this technique to interpret cerebrovascular pressure reactivity (CVPR), a surrogate of the brain's ability to autoregulate blood flow. We describe a physiological model-based approach to NIRS interpretation which predicts autoregulatory efficiency from a model parameter k_aut. Data from three critically brain-injured patients exhibiting a change in CVPR were investigated. An optimal value for k_aut was determined to minimise the difference between measured and simulated outputs. Optimal values for k_aut appropriately tracked changes in CVPR under most circumstances. Further development of this technique could be used to track CVPR providing targets for individualised management of patients with altered vascular reactivity, minimising secondary neurological insults.

BACKGROUND: Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this. METHODS: National, urban and rural data on HIV prevalence, the percentage of younger (15-24) and older (25-49) women and men reporting multiple (2+) partners in the past year, HIV prevalence among female sex workers (FSWs), men who have bought sex in the past year (clients), and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other. FINDINGS: National population HIV prevalence varies between 0 4-2 9% for men and 0 4-5.6% for women. ART coverage ranges from 6-23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence. INTERPRETATION: In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners.

BACKGROUND: The Avahan programme has provided HIV prevention activities, including condom promotion, to female sex workers (FSWs) in southern India since 2004. Evidence suggests Avahan averted 202,000 HIV infections over 4 years. For replicating this intervention elsewhere, it is essential to understand how the intervention's impact could have been optimised for different budget levels. METHODS: Behavioural data were used to determine how condom use varied for FSWs with different levels of intervention intensity. Cost data from 64 Avahan districts quantified how district-level costs related to intervention scale and intensity. A deterministic model for HIV transmission amongst FSWs and clients projected the impact and cost of intervention strategies for different scale and intensity, and identified the optimal strategies that maximise impact for different budget levels. RESULTS: As budget levels increase, the optimal intervention strategy is to first increase intervention intensity which achieves little impact, then scale-up coverage to high levels for large increases in impact, and lastly increase intensity further for small additional gains. The cost-effectiveness of these optimal strategies generally improves with increasing resources, while straying from these strategies can triple costs for the same impact. Projections suggest Avahan was close to being optimal, and moderate budget reductions (≥ 20%) would have reduced impact considerably (>40%). DISCUSSION: Our analysis suggests that tailoring the design of HIV prevention programmes for FSWs can improve impact, and that a certain level of resources are required to achieve demonstrable impact. These insights are critical for optimising the use of limited resources for preventing HIV.