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Background: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis., Aims: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence., Methods: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis., Results: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%])., Conclusion: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease., (© 2024. The Author(s).)

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s., (© 2024. The Author(s).)

Objectives: Uptake of influenza, pneumococcal and shingles vaccines in older adults vary across regions and socioeconomic backgrounds. In this study, we study the coverage and factors associated with vaccination uptake, as well as refusal in the unvaccinated population and their associations with ethnicity, deprivation, household size and health conditions., Design, Setting and Participants: This is a cross-sectional study of adults aged 65 years or older in England, using a large primary care database. Associations of vaccine uptake and refusal in the unvaccinated with ethnicity, deprivation, household size and health conditions were modelled using multivariable logistic regression., Outcome Measure: Influenza, pneumococcal and shingles vaccine uptake and refusal (in the unvaccinated)., Results: This study included 2 054 463 patients from 1318 general practices. 1 711 465 (83.3%) received at least one influenza vaccine, 1 391 228 (67.7%) pneumococcal vaccine and 690 783 (53.4%) shingles vaccine. Compared with White ethnicity, influenza vaccine uptake was lower in Chinese (OR 0.49; 95% CI 0.45 to 0.53), 'Other ethnic' groups (0.63; 95% CI 0.60 to 0.65), black Caribbean (0.68; 95% CI 0.64 to 0.71) and black African (0.72; 95% CI 0.68 to 0.77). There was generally lower vaccination uptake among more deprived individuals, people living in larger household sizes (three or more persons) and those with fewer health conditions. Among those who were unvaccinated, higher odds of refusal were associated with the black Caribbean ethnic group and marginally with increased deprivation, but not associated with higher refusal in those living in large households or those with lesser health conditions., Conclusion: Certain ethnic minority groups, deprived populations, large households and 'healthier' individuals were less likely to receive a vaccine, although higher refusal was only associated with ethnicity and deprivation but not larger households nor healthier individuals. Understanding these may inform tailored public health messaging to different communities for equitable implementation of vaccination programmes., Competing Interests: Competing interests: PST reports previous consultation with AstraZeneca and Duke-NUS outside the submitted work. KK is a Member of the Scientific Advisory Group for Emergencies (SAGE), Member of Independent SAGE, Director of the University of Leicester Centre for Black Minority Health and Trustee of the south Asian Health Foundation. JH-C is a member of several SAGE committees and chair of the risk stratification subgroup of the NERVTAG. She is an unpaid director of QResearch and founder and former medical director of ClinRisk Ltd (outside the submitted work). MP, AKC, HD-M, DS, TAR, FZ, BRS, SJG, CC, CG have no interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts from England and Canada and investigates potential explanatory factors for ethnic patterning of severe outcomes., Methods: We identified adults aged 18 to 99 years in the QResearch primary care (England) and Ontario (Canada) healthcare administrative population-based datasets (start of follow-up: 24th and 25th Jan 2020 in England and Canada, respectively; end of follow-up: 31st Oct and 30th Sept 2020, respectively). We harmonised the definitions and the design of two cohorts to investigate associations between ethnicity and COVID-19-related death, hospitalisation, and intensive care (ICU) admission, adjusted for confounders, and combined the estimates obtained from survival analyses. We calculated the 'percentage of excess risk mediated' by these risk factors in the QResearch cohort., Results: There were 9.83 million adults in the QResearch cohort (11,597 deaths; 21,917 hospitalisations; 2932 ICU admissions) and 10.27 million adults in the Ontario cohort (951 deaths; 5132 hospitalisations; 1191 ICU admissions). Compared to the general population, pooled random-effects estimates showed that South Asian ethnicity was associated with an increased risk of COVID-19 death (hazard ratio: 1.63, 95% CI: 1.09-2.44), hospitalisation (1.53; 1.32-1.76), and ICU admission (1.67; 1.23-2.28). Associations with ethnic groups were consistent across levels of deprivation. In QResearch, sociodemographic, lifestyle, and clinical factors accounted for 42.9% (South Asian) and 39.4% (Black) of the excess risk of COVID-19 death., Conclusion: International population-level analyses demonstrate clear ethnic inequalities in COVID-19 risks. Policymakers should be cognisant of the increased risks in some ethnic populations and design equitable health policy as the pandemic continues., (© 2023. The Author(s).)

There is an intriguing association between winter births and subsequent increased risk of schizophrenia. However, little is known about the environmental risk factors that contribute this month-of-birth effect. The aims of this study were to carry out a systematic review and meta-analysis of studies investigating the month-of-birth effect in schizophrenia and to explore possible factors such as latitude, daylight and infections that could explain this epidemiological observation. Medline, Embase and the Cochrane Library were searched for articles published up to December 23, 2021. Study selection, data extraction and analysis were undertaken according to Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Generic inverse-variance with random effects models were used to determine the risk ratios (RR) and 95% confidence intervals (CI) for each month-of-birth. Associations between variables latitude and daylight were investigated using linear regression and Kendall's rank correlation coefficients were calculated assess the relationship between monthly infections rates schizophrenia births. Ten studies were included in the meta-analysis encompassing 262,188 schizophrenia patients. We identified significantly higher number of schizophrenia births in December [1.04 (95%CI 1.00-1.08)], January [1.06 (95%CI 1.03-1.1)] and February [1.03 (95%CI 1.00-1.05)]. We did not find any association between latitude and the magnitude of the month-of-birth effect. On the other hand, we found a significant negative correlation between monthly severe enterovirus cases and schizophrenia births (tau -0.57, p = 0.0099) using data from Taiwan. This highlights a role for enterovirus infections in mediating the month-of-birth effect in schizophrenia and these results carry implications for disease prevention strategies., Competing Interests: None., (© 2022 The Authors.)

Background: We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people (CYP), within a systematic review and individual patient meta-analysis., Methods: We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).PROSPERO: CRD42021235338., Findings: 83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45-1.53) for 1 comorbidity; 2.58 (2.41-2.75) for 2 comorbidities; 2.97 (2.04-4.32) for ≥3 comorbidities. Corresponding odds ratios for death were: 2.15 (1.98-2.34) for 1 comorbidity; 4.63 (4.54-4.74) for 2 comorbidities and 4.98 (3.78-6.65) for ≥3 comorbidities. Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. IPD analysis demonstrated that, compared to children without co-morbidity, the risk difference of admission to critical care was increased in those with 1 comorbidity by 3.61% (1.87-5.36); 2 comorbidities by 9.26% (4.87-13.65); ≥3 comorbidities 10.83% (4.39-17.28), and for death: 1 comorbidity 1.50% (0.00-3.10); 2 comorbidities 4.40% (-0.10-8.80) and ≥3 co-morbidities 4.70 (0.50-8.90)., Interpretation: Hospitalised CYP at greatest vulnerability of severe disease or death with SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions., Funding: RH is in receipt of a fellowship from Kidney Research UK (grant no. TF&#95;010&#95;20171124). JW is in receipt of a Medical Research Council Fellowship (Grant No. MR/R00160X/1). LF is in receipt of funding from Martin House Children's Hospice (there is no specific grant number for this). RV is in receipt of a grant from the National Institute of Health Research to support this work (grant no NIHR202322). Funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript., Competing Interests: KL is the Programme Lead for the National Child Mortality Database. SK is the National Clinical Director for Children and Young People, NHS England and Improvement. ED is the Co-Principle Investigator for the Paediatric Intensive Care Audit Network., (© 2022 The Authors.)

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test., (© 2021. The Author(s).)

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10 -4 ) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10 -10 ). We found that these genes mapped to key biological processes, such as neuronal cell adhesion. We also identified cortical excitatory neurons and inhibitory interneurons as the most vulnerable cell types to the deleterious effects of this interaction. Subsequently, we used gene expression information from herpes simplex virus 1 infection of neuronal precursor cells as orthogonal evidence to support our findings and to demonstrate that schizophrenia-associated cell adhesion genes, PCDHA2, PCDHA3 and PCDHA5 , were downregulated following herpes simplex virus 1 infection. Collectively, our results provide novel evidence for a link between genetic and environmental risk factors in schizophrenia pathogenesis. These findings carry important implications for early preventative strategies in schizophrenia., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Importance: Although children mainly experience mild COVID-19 disease, hospitalization rates are increasing, with limited understanding of underlying factors. There is an established association between race and severe COVID-19 outcomes in adults in England; however, whether a similar association exists in children is unclear., Objective: To investigate the association between race and childhood COVID-19 testing and hospital outcomes., Design, Setting, Participants: In this cohort study, children (0-18 years of age) from participating family practices in England were identified in the QResearch database between January 24 and November 30, 2020. The QResearch database has individually linked patients with national SARS-CoV-2 testing, hospital admission, and mortality data., Exposures: The main characteristic of interest is self-reported race. Other exposures were age, sex, deprivation level, geographic region, household size, and comorbidities (asthma; diabetes; and cardiac, neurologic, and hematologic conditions)., Main Outcomes and Measures: The primary outcome was hospital admission with confirmed COVID-19. Secondary outcomes were SARS-CoV-2-positive test result and any hospital attendance with confirmed COVID-19 and intensive care admission., Results: Of 2 576 353 children (mean [SD] age, 9.23 [5.24] years; 48.8% female), 410 726 (15.9%) were tested for SARS-CoV-2 and 26 322 (6.4%) tested positive. A total of 1853 children (0.07%) with confirmed COVID-19 attended hospital, 343 (0.01%) were admitted to the hospital, and 73 (0.002%) required intensive care. Testing varied across race. White children had the highest proportion of SARS-CoV-2 tests (223 701/1 311 041 [17.1%]), whereas Asian children (33 213/243 545 [13.6%]), Black children (7727/93 620 [8.3%]), and children of mixed or other races (18 971/147 529 [12.9%]) had lower proportions. Compared with White children, Asian children were more likely to have COVID-19 hospital admissions (adjusted odds ratio [OR], 1.62; 95% CI, 1.12-2.36), whereas Black children (adjusted OR, 1.44; 95% CI, 0.90-2.31) and children of mixed or other races (adjusted OR, 1.40; 95% CI, 0.93-2.10) had comparable hospital admissions. Asian children were more likely to be admitted to intensive care (adjusted OR, 2.11; 95% CI, 1.07-4.14), and Black children (adjusted OR, 2.31; 95% CI, 1.08-4.94) and children of mixed or other races (adjusted OR, 2.14; 95% CI, 1.25-3.65) had longer hospital admissions (≥36 hours)., Conclusions and Relevance: In this large population-based study exploring the association between race and childhood COVID-19 testing and hospital outcomes, several race-specific disparities were observed in severe COVID-19 outcomes. However, ascertainment bias and residual confounding in this cohort study should be considered before drawing any further conclusions. Overall, findings of this study have important public health implications internationally.

Maternal infection is thought to increase the risk of non-affective psychosis including schizophrenia. However, observational studies have produced conflicting results and little is known about the importance of timing of infection in mediating subsequent risk. In this study, we carried out a meta-analysis of observational studies to investigate the risk of maternal infection and subsequent risk of non-affective psychosis. Using seven cohort studies, we found that maternal infection during gestation increased the risk of non-affective psychosis [relative risk (RR): 1.28 (95% CI:1.05-1.57, p = 0.02, I 2  = 36%)]. A subgroup analysis identified that there was greater risk for schizophrenia alone [RR: 1.65 (95% CI:1.23-2.22, p = 0.0008, I 2  = 0%)]. In addition, infection during the second trimester resulted in increased risk [RR: 1.63 (95% CI:1.07-2.48, p = 0.02, I 2  = 7%)], whilst risk during the first and third trimesters did not meet statistical significance. This study highlights maternal infection in gestation as an important environmental risk factor for non-affective psychosis and our findings carry important implications for future disease prevention strategies., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Recent evidence suggests that ethnic minority groups are disproportionately at increased risk of hospitalisation and death from SARS-CoV-2 infection. Population-based evidence on potential explanatory factors across minority groups and within subgroups is lacking. This study aims to quantify the association between ethnicity and the risk of hospitalisation and mortality due to COVID-19., Methods and Analysis: This is a retrospective cohort study of adults registered across a representative and anonymised national primary care database (QResearch) that includes data on 10 million people in England. Sociodemographic, deprivation, clinical and domicile characteristics will be summarised and compared across ethnic subgroups (categorised as per 2011 census). Cox models will be used to calculate HR for hospitalisation and COVID-19 mortality associated with ethnic group. Potential confounding and explanatory factors (such as demographic, socioeconomic and clinical) will be adjusted for within regression models. The percentage contribution of distinct risk factor classes to the excess risks seen in ethnic groups/subgroups will be calculated., Ethics and Dissemination: The study has undergone ethics review in accordance with the QResearch agreement (reference OX102). Findings will be disseminated through peer-reviewed manuscripts, presentations at scientific meetings and conferences with national and international stakeholders., Competing Interests: Competing interests: JH-C is founder and director of QResearch database, which is a not-for-profit organisation with EMIS (leading commercial supplier of IT for 55% of general practices in the UK). JH-C is co-owner of ClinRisk and was a paid director until June 2019. ClinRisk develops open and closed source software to ensure the reliable and updatable implementation of clinical risk equations within clinical computer systems to help improve patient care, outside the submitted work. KK is national lead for NIHR ARC ethnicity and diversity, Director for the University of Leicester Centre for BME Health, Trustee of the South Asian Health Foundation and member of the Independent SAGE. The authors declare that no support from any organisation and no financial relationships have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess differences across educational outcomes in survivors of childhood cancer (CCS) compared with peers., Design: Systematic review and meta-analysis of observational studies., Data Sources and Study Selection: Medline, EMBASE, ERIC, CINAHL and PsycInfo from inception to 1st August 2018. Any peer reviewed, comparative study with a population of any survivor of childhood cancer, from high-economy countries, reporting outcomes on educational attainment, were selected., Results: 26 studies representing 28 434 CCS, 17 814 matched controls, 6582 siblings and six population studies from 11 high-income countries, which have similar access to education and years of mandatory schooling as reported by the Organisation for Economic Cooperation and Development, were included. CCS were more likely to remain at compulsory level (OR 1.36, 95% CI 1.26 to 1.43) and less likely to complete secondary (OR 0.93, 95% CI 0.87 to 1.0) and tertiary level education (OR 0.87, 95% CI 0.78 to 0.98). They were more likely to require special educational needs (OR 2.47, 95% CI 1.91 to 3.20). Subgroup analyses revealed that survivors, irrespective of central nervous system (CNS) involvement, were less likely to progress onto secondary level compared with cancer-free peers (OR 1.77. 95% CI 1.46 to 2.15; OR 1.19, 95% CI 1.00 to 1.42, respectively). This, however, changed at tertiary level where those with CNS involvement continued to perform worse (OR 0.61, 95% CI 0.55 to 0.68) but those without appeared to perform similarly to their peers (OR 1.12, 95% CI 1.0 to 1.25)., Conclusions: Compared with controls, we have elucidated significant differences in educational attainment in survivors. This is sustained across different countries, making it an international issue. CNS involvement plays a key role in educational achievement. Clinicians, teachers and policymakers should be made aware of differences and consider advocating for early educational support for survivors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Objectives: To determine whether antibiotics are prescribed appropriately for acute tonsillitis in an emergency department (ED)., Methods: Cross-sectional observational study in large district general hospital in London. Patients diagnosed and coded with 'acute tonsillitis' in the ED over a 3-month period in 2015. Medical records were reviewed for Centor criteria, which is a clinical scoring system to guide antibiotic prescribing in UK general practice. Drug charts were reviewed for the specific antibiotic(s) prescribed, and throat swab (TS) cultures were recorded., Results: 273/389 patients with tonsillitis were analysed-186 children, 87 adults. Exclusions were missing patient records (86), patients had/awaiting tonsillectomy (22), receiving antibiotics (6) and immunocompromised (2). Centor score (CS) was not recorded for any patient. Based on derived CS from documented signs/symptoms, antibiotics were prescribed inappropriately to 196/273 patients (80%; 95% CI 74% to 85%) including broad-spectrum antibiotics to 25%. These included co-amoxiclav (18%), amoxicillin (6%), azithromycin (0.5%) and ceftriaxone (0.5%). TSs were taken in 66/273(24%) patients; 10/66 were positive for group A streptococcus (GAS). However, 48/56 GAS negative patients were prescribed antibiotics., Conclusions: CS was not being used in the ED to guide antibiotic prescribing for acute tonsillitis. Antibiotic prescribing was based on clinical judgement. Based on derived CS (<3), 80% of patients were inappropriately prescribed antibiotics, particularly broad-spectrum antibiotics. Further studies need to assess use of CS to guide antibiotic prescription in ED. TSs were commonly performed in the ED but did not either improve diagnosis or guide antibiotic prescription., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic Encephalopathy, is a subtle cognitive defect found in 30-70 % of cirrhosis patients. It has been linked to poor quality of life, impaired fitness to drive, and increased mortality: treatment is possible. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for use in a clinical setting. We investigated whether measurement of saccadic latency distributions might be a viable alternative. We collected data on 35 cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of clinically overt encephalopathy, and 36 age-matched healthy controls. Performance on standard psychometric tests was evaluated to determine those patients with CHE as defined by the World Congress of Gastroenterology. We then compared visually-evoked saccades between those with CHE and those without, as well as reviewing blood test results and correlating saccadic latencies with biochemical parameters and prognostic scores. Cirrhosis patients have significantly longer median saccadic latencies than healthy controls. Those with CHE had significantly prolonged saccadic latencies when compared with those without CHE. Analysis of a cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75 % and a specificity of 75 %. We concluded that analysis of a cirrhosis patient's saccadic latency distributions is a fast and objective measure that can be used as a diagnostic tool for CHE. This improved early diagnosis could direct avoidance of high-risk activities such as driving, and better inform treatment strategies.