Objective: To delineate the risk to child IQ associated with frequently prescribed antiepileptic drugs.Methods: Children born to women with epilepsy (n 5 243) and women without epilepsy (n 5 287) were recruited during pregnancy and followed prospectively. Of these, 408 were blindly assessed at 6 years of age. Maternal and child demographics were collected and entered into statistical models.Results: The adjusted mean IQ was 9.7 points lower (95% confidence interval [CI] 24.9 to 214.6; p , 0.001) for children exposed to high-dose (.800 mg daily) valproate, with a similar significant effect observed for the verbal, nonverbal, and spatial subscales. Children exposed to high-dose valproate had an 8-fold increased need of educational intervention relative to control children (adjusted relative risk, 95% CI 8.0, 2.5-19.7; p , 0.001). Valproate at doses ,800 mg daily was not associated with reduced IQ, but was associated with impaired verbal abilities (25.6, 95% CI 211.1 to 20.1; p 5 0.04) and a 6-fold increase in educational intervention (95% CI 1.4-18.0; p 5 0.01). In utero exposure to carbamazepine or lamotrigine did not have a significant effect on IQ, but carbamazepine was associated with reduced verbal abilities (24.2, 95% CI 20.6 to 27.8; p 5 0.02) and increased frequency of IQ ,85.Conclusions: Consistent with data from younger cohorts, school-aged children exposed to valproate at maternal doses more than 800 mg daily continue to experience significantly poorer cognitive development than control children or children exposed to lamotrigine and carbamazepine. Antiepileptic drugs (AEDs) are associated with teratogenic risk to the development of the fetus, with the prevalence of major congenital malformations differing by treatment type and dose. Determining the association between exposure to AEDs and child cognitive functioning represents a challenge, and a number of different methodologies have been utilized in its investigation including case studies, 2-4 retrospective studies, 5,6 and prospective studies. 7-15 Despite limitations, 16 there is growing evidence that exposure to sodium valproate (VPA) in utero is associated with significantly poorer functioning. [10][11][12]15,17 Prospective studies consistently document that VPA is associated with an increase in risk of cognitive impairment in young children, 10,12,15 but any longer-term effects are unlikely to be comprehensively documented until the children studied are of school age, when cognitive development is more stable.10 In a comparison across AED monotherapies, a significantly poorer IQ in school-aged children exposed in utero to

The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug (AED) treatments. A prospective cohort of women with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until six years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (6/50, 12.0%; aOR 6.05, 95%CI 1.65–24.53; p=0.007) and in those exposed to polytherapy with sodium valproate (3/20, 15.0%; aOR 9.97, 95%CI 1.82–49.40; p=0.005) compared to control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found amongst children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium valproate exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium valproate is a treatment option.

Preconception counseling should include discussion of neurodevelopmental outcomes for specific treatments and their doses and women should be made aware of the limited nature of the evidence base for newer antiepileptic drugs.

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 >10 6 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>10 4 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<10 4 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.

Background Visual problems are an under-reported sequela following stroke. The aim of this study is to report annual incidence and point prevalence of visual problems in an acute adult stroke population and to explore feasibility of early timing of visual assessment. Methods and findings Multi-centre acute stroke unit, prospective, epidemiology study (1 st July 2014 to 30 th June 2015). Orthoptists reviewed all patients with assessment of visual acuity, visual fields, ocular alignment, ocular motility, visual inattention and visual perception. 1033 patients underwent visual screening at a median of 3 days (IQR 2) and full visual assessment at a median of 4 days (IQR 7) after the incident stroke: 52% men, 48% women, mean age 73 years and 87% ischaemic strokes. Excluding pre-existent eye problems, the incidence of new onset visual sequelae was 48% for all stroke admissions and 60% in stroke survivors. Three quarters 752/1033 (73%) had visual problems (point prevalence): 56% with impaired central vision, 40% eye movement abnormalities, 28% visual field loss, 27% visual inattention, 5% visual perceptual disorders. 281/1033 (27%) had normal eye exams. Conclusions Incidence and point prevalence of visual problems in acute stroke is alarmingly high, affecting over half the survivors. For most, visual screening and full visual assessment was achieved within about 5 days of stroke onset. Crucial information can thus be provided on visual status and its functional significance to the stroke team, patients and carers, enabling early intervention.

Background Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. MethodsIn this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260. FindingsBetween March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32•3% (95% CI 31•8-32•7) in March 9 to April 26, 2020, to 16•4% (15•0-17•8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0•68 [95% CI 0•65-0•71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10•2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22•2%, OR 0•95 (0•94-0•95) of the reduction in in-hospital mortality.Interpretation The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain.

The current study indicates that children exposed to LEV in utero were superior in their language and motor development in comparison to children exposed to VPA. This information should be used collaboratively between health care professionals and WWE when deciding on women's preferred choice of antiepileptic drug.

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.