The Paediatric Vault Score (PVS)-A Novel Scoring Tool for Prioritisation of Surgical Management of Craniosynostosis Patients.

Craniosynostosis is the premature fusion of the skull sutures, resulting in abnormal skull shape and volume. Timely management is a priority in avoiding raised intracranial pressure which can result in blindness and neurodevelopmental delay. Due to the COVID-19 pandemic, theater access was reduced. A risk stratification scoring system was thus devised to score patients attending surgery and aid in prioritization according to surgical need. The authors present the Paediatric Vault Score (PVS), which can also be customized to each unit's individual protocols. Ten patients on the waiting list were randomly selected and their clinical information was summarized in uniform anonymized reports. Six craniofacial consultants were selected as assessors and given 1 week to independently rank the patients from 1 to 10. Each scorer's ranking was verified against the PVS template and concordance was analyzed using the Kendall tau correlation coefficient (KT). Three cycles of the scoring process were carried out. Improvements were made to the scoring tool following cycle 1. Cycle 1 revealed 2 clinicians to be concordant with the PVS system and 4 to be discordant. Cycle 2 revealed all 6 clinicians to be concordant, with a mean KT score of 0.61. The final cycle revealed all 6 clinicians to be concordant, with a mean KT score of 0.70. Four scorers increased their concordance once the scoring sheet was introduced. Kendall's correlation of concordance calculated the interrater reliability to be 0.81. The PVS is the first known vault scoring system to aid in risk stratification and waiting list prioritization.

Evaluating social and spatial inequalities of large scale rapid lateral flow SARS-CoV-2 antigen testing in COVID-19 management: an observational study of Liverpool, UK (November 2020 to January 2021)

BackgroundAsymptomatic transmission of SARS-CoV-2 poses a significant burden on managing the spread of COVID-19. Few studies have evaluated the impact of testing for asymptomatic COVID-19 among large populations or whole cities using empirical data. No study to our knowledge has considered if such interventions result in or exacerbate existing socioeconomic inequalities. The aim of our study is to explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19 in Liverpool between 6th November 2020 and 31st January 2021.MethodsLinked pseudonymised records for asymptomatic residents in Liverpool (UK) who received a LFT for COVID-19 between 6th November 2020 to 31st January 2021 were accessed using the Combined Intelligence for Population Health Action (CIPHA) data resource. Bayesian Hierarchical Poisson Besag, York, and Mollié models were used to estimate ecological associations for uptake and positivity of testing.Results214 525 residents (43%) received a LFT identifying 5557 individuals as positive cases of COVID-19 (1.3%). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake and repeat testing were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for ‘Mixed’ ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas.ConclusionOur study provides the first substantial evidence on inequalities involved in large-scale asymptomatic rapid testing of populations for SARS-CoV-2. Large-scale voluntary asymptomatic community testing saw social, ethnic, and spatial inequalities in an ‘inverse care’ pattern, but with an added digital exclusion factor. While test uptake was popular, there was a disconnect between the populations accessing testing and those experiencing harms relating to COVID-19. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access.

Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study.

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients <60 years. Relative to those >60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials.

Protocol for DexEnceph: a randomised controlled trial of dexamethasone therapy in adults with herpes simplex virus encephalitis.

INTRODUCTION: Herpes simplex virus (HSV) encephalitis is a rare severe form of brain inflammation that commonly leaves survivors and their families with devastating long-term consequences. The virus particularly targets the temporal lobe of the brain causing debilitating problems in memory, especially verbal memory. It is postulated that immunomodulation with the corticosteroid, dexamethasone, could improve outcomes by reducing brain swelling. However, there are concerns (so far not observed) that such immunosuppression might facilitate increased viral replication with resultant worsening of disease. A previous trail closed early because of slow recruitment. METHOD: DexEnceph is a pragmatic multicentre, randomised, controlled, open-label, observer-blind trial to determine whether adults with HSV encephalitis who receive dexamethasone alongside standard antiviral treatment with aciclovir for have improved clinical outcomes compared with those who receive standard treatment alone. Overall, 90 patients with HSV encephalitis are being recruited from a target of 45 recruiting sites; patients are randomised 1:1 to the dexamethasone or control arms of the study. The primary outcome measured is verbal memory as assessed by the Weschler Memory Scale fourth edition Auditory Memory Index at 26 weeks after randomisation. Secondary outcomes are measured up to 72 weeks include additional neuropsychological, clinical and functional outcomes as well as comparison of neuroimaging findings. Patient safety monitoring occurs throughout and includes the detection of HSV DNA in cerebrospinal fluid 2 weeks after randomisation, which is indicative of ongoing viral replication. Innovative methods are being used to ensure recrutiment targets are met for this rare disease. DISCUSSION: DexEnceph aims to be the first completed randomised controlled trial of corticosteroid therapy in HSV encephalitis. The results will provide evidence for future practice in managing adults with the condition and has the potential to improve outcomes . ETHICS AND DISSEMINATION: The trial has ethical approval from the UK National Research Ethics Committee (Liverpool Central, REF: 15/NW/0545, 10 August 2015). Protocol V.2.1, July 2019. The results will be published and presented as soon as possible on completion. TRIAL REGISTRATION NUMBERS: ISRCTN11774734, EUDRACT 2015-001609-16.

Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study.

OBJECTIVE: To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. DESIGN: Observational cohort study. SETTING: Community LFT pilot at covid-19 testing sites in Liverpool, UK. PARTICIPANTS: 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. INTERVENTIONS: Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. RESULTS: Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >106 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>104 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<104 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. CONCLUSIONS: The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.

Evaluating social and spatial inequalities of large scale rapid lateral flow SARS-CoV-2 antigen testing in COVID-19 management: An observational study of Liverpool, UK (November 2020 to January 2021).

BACKGROUND: Large-scale asymptomatic testing of communities in Liverpool (UK) for SARS-CoV-2 was used as a public health tool for containing COVID-19. The aim of the study is to explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19. METHODS: Linked pseudonymised records for asymptomatic residents in Liverpool who received a LFT for COVID-19 between 6th November 2020 to 31st January 2021 were accessed using the Combined Intelligence for Population Health Action resource. Bayesian Hierarchical Poisson Besag, York, and Mollié models were used to estimate ecological associations for uptake and positivity of testing. FINDINGS: 214 525 residents (43%) received a LFT identifying 5192 individuals as positive cases of COVID-19 (1.3% of tests were positive). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for 'Mixed' ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas. INTERPRETATION: Large-scale voluntary asymptomatic community testing saw social, ethnic, digital and spatial inequalities in uptake. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access. FUNDING: Department of Health and Social Care (UK) and Economic and Social Research Council.