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Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events. New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination., Author(s): C. R. Simpson [sup.1] [sup.2] , T. Shi [sup.2] , E. Vasileiou [sup.2] , S. V. Katikireddi [sup.3] , S. Kerr [sup.2] , E. Moore [sup.4] , C. McCowan [...]

As the manufactured parts in aerospace and automotive industries tend to be larger and more complex, the inspection process becomes a difficult and timeconsuming one. To decrease inspection costs and time, the optimisation of the required Surface Sampling Points (SSP) is crucial. This paper describes a data sampling technique (DST) for the inspection of waving surfaces of parts. This technique provides the minimum number of SSP required to reconstruct accurately the waving surface. The developed DST comprises two steps: (1) trigonometric polynomial approximation of the curvilinear segments, at certain orthogonal sections on the waving surface, and (2) estimation of the critical frequency of the approximated waving sections, leading to the minimum number of SSP. The pilot implementation of the DST has been performed on a waving wing surface and has been tested using industrial data. The accuracy and the efficiency of the DST has been estimated through (1) the comparison of theoretical (CAD) profiles with the surface profiles measured using the current sampling method and with the ones derived using the developed sampling technique, and (2) the comparison of the sampling intervals extracted by DST and the ones extracted by analysing past measurements with Discrete Fourier Transform (DFT). [ABSTRACT FROM AUTHOR]

Landslide phenomena are strongly affected by physical factors such as the precipitation (mainly rainfall) combined with the geological structure that exists in a region. In addition, the influence of the anthropogenic activities on the natural environment is proven to be a crucial factor in the appearance of geological failures. This study examines the phenomenon of landslides and in particular the distinguishment of those factors which act as an activating cause. In order to achieve this goal three factors were examined as very important. The case study that was investigated was Agrafa Municipality. Rainfall data of fifty year-period, the historical data of landslides in the area and the integrated system of data management system of Geographic Information Systems were used for the evaluation of all these. The models which were developed to achieve the final result are as follows: i) multi-criteria analysis with weighting factors, ii) analytical hierarchy process method and iii) use of same methods without the participation of hydrogeological factors. The results clearly demonstrate the initial belief, as the final hazard maps verify the importance of rainfall in landslides. [ABSTRACT FROM AUTHOR]

Managed Aquifer Recharge is a wide-spread well-established groundwater engineering method which is largely seen as sound and sustainable solution to water scarcity hydrologically sensitive areas, such as the Circum Mediterranean. The process of site selection for the installation of a MAR facility is of paramount importance for the feasibility and effectiveness of the project itself, especially when the facility will include the use of waters of impaired quality as a recharge source, as in the case of Soil-Aquifer-Treatment systems. The main objective of this study is to present the developed framework of a multi-criteria Decision Support System (DSS) that integrates within a dynamic platform the main groundwater engineering parameters associated with MAR applications together with the general geographical features which determine the effectiveness of such a project. The proposed system will provide an advanced coupled DSS-GIS tool capable of handling local MAR-related issues -such as hydrogeology, topography, soil, climate etc., and spatially distributed variables -such as societal, economic, administrative, legislative etc., with special reference to Soil-Aquifer-Treatment technologies. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic and the ensuing implementation of control measures caused widespread societal disruption. These disruptions may also have affected community transmission and seasonal circulation patterns of endemic respiratory viruses., Objective: We aimed to investigate the impact of COVID-19-related disruption on influenza-related emergency hospital admissions and deaths in Wales in the first 2 years of the pandemic., Methods: A descriptive analysis of influenza activity was conducted using anonymized pathology, hospitalization, and mortality data from the Secure Anonymised Information Linkage Databank in Wales. The annual incidence of emergency hospitalizations and deaths with influenza-specific diagnosis codes between January 1, 2015, and December 31, 2021, was estimated. Case definitions of emergency hospitalization and death required laboratory confirmation with a polymerase chain reaction test. Trends of admissions and deaths were analyzed monthly and yearly. We conducted 2 sensitivity analyses by extending case definitions to include acute respiratory illnesses with a positive influenza test and by limiting admissions to those with influenza as the primary diagnosis. We also examined yearly influenza testing trends to understand changes in testing behavior during the pandemic., Results: We studied a population of 3,235,883 Welsh residents in 2020 with a median age of 42.5 (IQR 22.9-61.0) years. Influenza testing in Wales increased notably in the last 2 months of 2020, and particularly in 2021 to 39,720 per 100,000 people, compared to the prepandemic levels (1343 in 2019). The percentage of influenza admissions matched to an influenza polymerase chain reaction test increased from 74.8% (1890/2526) in 2019 to 85.2% (98/115) in 2021. However, admissions with a positive test per 100,000 population decreased from 17.0 in 2019 to 2.7 and 0.6 in 2020 and 2021, respectively. Similarly, deaths due to influenza with a positive influenza test per 100,000 population decreased from 0.4 in 2019 to 0.0 in 2020 and 2021. Sensitivity analyses showed similar patterns of decreasing influenza admissions and deaths in the first 2 years of the COVID-19 pandemic., Conclusions: Nonpharmaceutical interventions to control COVID-19 were associated with a substantial reduction in the transmission of the influenza virus, with associated substantial reductions in hospital cases and deaths observed. Beyond the pandemic context, consideration should be given to the role of nonpharmaceutical community-driven interventions to reduce the burden of influenza., (© Mohammad Alsallakh, Davies Adeloye, Eleftheria Vasileiou, Shanya Sivakumaran, Ashley Akbari, Ronan A Lyons, Chris Robertson, Igor Rudan, Gwyneth A Davies, Aziz Sheikh. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Preeclampsia is a human-specific hypertensive disorder of gestation. It is associated with short-term adverse effects in the fetus and long-term complications in the neonate, mainly due to disrupted blood flow during critical periods of intrauterine development. An ischemic event in the uterus can affect many systems of the fetus, including a small bowel involvement. We present a case of a preterm, small for gestational age neonate with severe intrauterine growth restriction, small bowel stenosis, and volvulus without malrotation, born to a mother with severe preeclampsia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Babacheva et al.)

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct demyelinating disease of the central nervous system. Immunoglobulin (Ig) has been used as a maintenance therapy to prevent relapses in MOGAD, but the impact of Ig on serum MOG-IgG titers is unclear., Objective: To characterize the variation in serum MOG-IgG titers after initiation of Ig treatment in people with MOGAD., Methods: We conducted a retrospective study of 10 patients with a diagnosis of MOGAD and available serum MOG-IgG titers before and after initiation of maintenance Ig treatment., Results: We found that most of the patients remained MOG-IgG seropositive while on Ig treatment with a reduced or unchanged titer, despite a lack of disease activity., Conclusions: This case series suggests that the mechanism of action of Ig therapy in MOGAD is not exclusively dependent on MOG-IgG titer reduction., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.R. has served on scientific advisory boards for Horizon Therapeutics. E.V., P.B., G.A., H.C., W.S., A.K., and I.K. have nothing to disclose. E.S.S. has received speaker honoraria from Alexion and Viela Bio, and has served on scientific advisory boards for Alexion, Viela Bio, Horizon Therapeutics, and Genentech.

Introduction: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy. Despite high cure rates, several questions remain regarding predisposition, response to treatment, and prognosis of the disease. The role of intermediary metabolism in the individualized mechanistic pathways of the disease is unclear. We have hypothesized that children with any (sub)type of ALL have a distinct metabolomic fingerprint at diagnosis when compared: (i) to a control group; (ii) to children with a different (sub)type of ALL; (iii) to the end of the induction treatment., Materials and Methods: In this prospective case-control study (NCT03035344), plasma and urinary metabolites were analyzed in 34 children with ALL before the beginning (D0) and at the end of the induction treatment (D33). Their metabolic fingerprint was defined by targeted analysis of 106 metabolites and compared to that of an equal number of matched controls. Multivariate and univariate statistical analyses were performed using SIMCAP and scripts under the R programming language., Results: Metabolomic analysis showed distinct changes in patients with ALL compared to controls on both D0 and D33. The metabolomic fingerprint within the patient group differed significantly between common B-ALL and pre-B ALL and between D0 and D33, reflecting the effect of treatment. We have further identified the major components of this metabolic dysregulation, indicating shifts in fatty acid synthesis, transfer and oxidation, in amino acid and glycerophospholipid metabolism, and in the glutaminolysis/TCA cycle., Conclusions: The disease type and time point-specific metabolic alterations observed in pediatric ALL are of particular interest as they may offer potential for the discovery of new prognostic biomarkers and therapeutic targets.

The occurrence, mobilization, and origin of Potentially Toxic Eelements (PTEs) in the environment is always a difficult research question that has not been fully addressed to date; solving this problem would be a major achievement for environmental science and pollution research, a significant scientific breakthrough, and an important contribution to environmental analysis and monitoring. The lack of a holistic methodology that uses chemical analysis to determine the origin of each PTE in the environment is the main motivation for this project. Therefore, the hypothesis tested here is to develop a scientific approach applied to each PTE to determine whether its origin is geogenic (i.e., water-rock interaction with dominance of silicate or carbonate mineral phases) or anthropogenic (i.e., agricultural practices, wastewater, industrial activities). A total of 47 groundwater samples from the Psachna Basin in central Euboea, Greece, were used and plotted on geochemical mole ratio diagrams (i.e., Si/NO 3 vs. Cl/HCO 3 ) and used to perform a robust geochemical modeling analysis. The proposed method showed that elevated groundwater concentrations of various PTEs in groundwater were mainly related to intensive fertilization (e.g., Cr, U), water-rock interaction (e.g., Ni), and saltwater intrusion. (i.e., As, Se). This work highlights that a comprehensive framework with sophisticated molar ratios combined with modern statistical methods, multi-isotope signatures, and geochemical modeling could provide answers to unresolved scientific questions about the origin of PTEs in water resources and improve environmental resilience., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function., Methods: In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures., Results: A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: -4.4 letters [95% CI; -8.5 to -0.3]; P = 0.04, 1.25% contrast: -6.8 letters [95%CI; -12 to -1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = -0.31; P = 0.50, 1.25% contrast: r = -0.34; P = 0.45, GCIPL: r = -0.04; P = 0.94)., Conclusions: Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Purpose: To quantify the associations of myopia with longitudinal changes in retinal layer thicknesses in people with multiple sclerosis (PwMS) and healthy controls (HC)., Methods: A cohort of PwMS and HC with recorded refractive error (RE) prospectively scanned on Cirrus HD-OCT at the Johns Hopkins MS Center was assessed for inclusion. Exclusion criteria included OCT follow-up < 6 months, ocular comorbidities, incidental OCT pathologies, and inadequate scan quality. Eyes were classified as having high myopia (HM) (RE≤ -6 diopters), low myopia (LM) (RE> -6 and ≤ -3 diopters), or no myopia (NM) (RE> -3 and ≤ +2.75). Linear mixed-effects regression models were used in analyses., Results: A total of 213 PwMS (eyes: 67 HM, 98 LM, 207 NM) and 80 HC (eyes: 26 HM, 37 LM, 93 NM) were included. Baseline average ganglion cell/inner plexiform (GCIPL) and peri-papillary retinal nerve fiber layer (pRNFL) thicknesses were lower in MS HM compared with MS NM (diff: -3.2 µm, 95% CI: -5.5 to -0.8, p  = 0.008 and -5.3 µm, 95% CI: -9.0 to -1.7, p  = 0.004, respectively), and similarly in HC HM, as compared with HC NM. Baseline superior, inferior, and nasal pRNFL thicknesses were lower in HM compared with NM, while temporal pRNFL thickness was higher, both in MS and HC (MS: 7.1 µm, 95% CI: 2.7-11.6, p  = 0.002; HC: 4.7 µm, 95% CI: -0.3 to 9.7, p  = 0.07). No longitudinal differences in rates of GCIPL change were noted between HM and LM vs. NM, either in MS or HC., Conclusion: Cross-sectional differences in average GCIPL and pRNFL thicknesses are commonly seen in people with HM as compared to reference normative values from people with NM and can lead to false attribution of pathology if RE is not taken into account. However, our study suggests that longitudinal changes in average GCIPL thickness in PwMS with myopia are similar in magnitude to PwMS with NM, and therefore are appropriate for monitoring disease-related pathology.

Objective: To explore longitudinal changes in brain volumetric measures and retinal layer thicknesses following acute optic neuritis (AON) in people with multiple sclerosis (PwMS), to investigate the process of trans-synaptic degeneration, and determine its clinical relevance., Methods: PwMS were recruited within 40 days of AON onset (n = 49), and underwent baseline retinal optical coherence tomography and brain magnetic resonance imaging followed by longitudinal tracking for up to 5 years. A comparator cohort of PwMS without a recent episode of AON were similarly tracked (n = 73). Mixed-effects linear regression models were used., Results: Accelerated atrophy of the occipital gray matter (GM), calcarine GM, and thalamus was seen in the AON cohort, as compared with the non-AON cohort (-0.76% vs -0.22% per year [p = 0.01] for occipital GM, -1.83% vs -0.32% per year [p = 0.008] for calcarine GM, -1.17% vs -0.67% per year [p = 0.02] for thalamus), whereas rates of whole-brain, cortical GM, non-occipital cortical GM atrophy, and T2 lesion accumulation did not differ significantly between the cohorts. In the AON cohort, greater AON-induced reduction in ganglion cell+inner plexiform layer thickness over the first year was associated with faster rates of whole-brain (r = 0.32, p = 0.04), white matter (r = 0.32, p = 0.04), and thalamic (r = 0.36, p = 0.02) atrophy over the study period. Significant relationships were identified between faster atrophy of the subcortical GM and thalamus, with worse visual function outcomes after AON., Interpretation: These results provide in-vivo evidence for anterograde trans-synaptic degeneration following AON in PwMS, and suggest that trans-synaptic degeneration may be related to clinically-relevant visual outcomes. ANN NEUROL 2023;93:76-87., (© 2022 American Neurological Association.)

Objective: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD., Methods: Eighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N = 66 and HCs: N = 103) and (2) Cirrus high-definition OCT (MOGAD: N = 14 and HCs: N = 36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified., Results: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HCs (p < 0.001). MOGAD-NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow-up up to 3 years), MOGAD-ON with ON within the last 6-12 months before baseline exhibited greater pRNFL thinning than MOGAD-ON with an ON greater than 12 months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort., Interpretation: Our study suggests the absence of attack-independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476-485., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: In July 2021, a new variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the Delta lineage was detected in the United Kingdom (UK), named AY.4.2 or "Delta plus". By October 2021, the AY.4.2 variant accounted for approximately 10-11% of cases in the UK. AY.4.2 was designated as a variant under investigation by the UK Health and Security Agency on 20 October 2021. This study aimed to investigate vaccine effectiveness (VE) against symptomatic COVID-19 (Coronavirus disease 2019) infection and COVID-19 hospitalisation/death for the AY.4.2 variant., Methods: We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE-II) platform to estimate the VE of the ChAdOx1, BNT162b2, and mRNA-1273 vaccines against symptomatic infection and severe COVID-19 outcomes in adults. The study was conducted from June 8 to October 25, 2021. We used a test-negative design (TND) to estimate VE against reverse transcriptase polymerase chain reaction (RT-PCR) confirmed symptomatic SARS-CoV-2 infection while adjusting for sex, socioeconomic status, number of coexisting conditions, and splines in time and age. We also performed a cohort study using a Cox proportional hazards model to estimate VE against a composite outcome of COVID-19 hospital admission or death, with the same adjustments., Results: We found an overall VE against symptomatic SARS-CoV-2 infection due to AY.4.2 of 73% (95% confidence interval (CI) = 62-81) for >14 days post-second vaccine dose. Good protection against AY.4.2 symptomatic infection was observed for BNT162b2, ChAdOx1, and mRNA-1273. In unvaccinated individuals, the hazard ratio (HR) for COVID-19 hospital admission or death from AY.4.2 among community detected cases was 1.77 (95% CI = 1.02-3.07) relative to unvaccinated individuals who were infected with Delta, after adjusting for multiple potential confounders. VE against AY.4.2 COVID-19 admissions or deaths was 87% (95% CI = 74-93) >28 days post-second vaccination relative to unvaccinated., Conclusions: We found that AY.4.2 was associated with an increased risk of COVID-19 hospitalisations or deaths in unvaccinated individuals compared with Delta and that vaccination provided substantial protection against symptomatic SARS-CoV-2 and severe COVID-19 outcomes following Delta AY.4.2 infection. High levels of vaccine uptake and protection offered by existing vaccines, as well as the rapid emergence of the Omicron variant may have contributed to the AY.4.2 variant never progressing to a variant of concern., Competing Interests: Competing interests: AS and CR are members of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and AS its Standing Committee on Pandemics. AS is also a member of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG). AS is a member of AstraZeneca’s Thrombotic Thrombocytopenic Taskforce. All AS’ roles are unremunerated. CR and MW are members of SPI-M. The authors completed the ICMJE Unified Competing Interest Form (available upon request from the corresponding author) and declare no further conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Introduction: COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID., Methods and Analysis: We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID., Ethics and Dissemination: The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID., Competing Interests: Competing interests: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is a member of the UK Government’s Risk Stratification Subgroup and Astra-Zeneca's Thrombotic Thrombocytopenic Taskforce. All roles are unremunerated. SVK was co-chair of the Scottish Government’s Expert Reference Group on Ethnicity and COVID-19 and a member of the UK Government’s Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mucormycosis has emerged as an increasingly important fungal disease for immunocompromised children and neonates, with the cutaneous form being one of its most common presentations., Methods: We present a cutaneous mucormycosis case in a 10-year-old girl and analyse reports of single cases and case series of cutaneous mucormycosis in ≤16-year-old patients, recorded in PUBMED from 1953 to 2020, for epidemiology, risk factors, diagnostic and therapeutic procedures and outcome., Results: 113 cases were enrolled. Median age was 5 years (Interquartile Range [IQR] 10.9), without gender predominance. Underlying conditions were haematologic malignancies/disorders (25.7%), prematurity (23%), solid organ transplantation (3.5%), diabetes mellitus type 1 (4.4%), immunodeficiency and other diseases (14.2%), and no underlying conditions (29.2%). Inoculation occurred through major trauma (12.4%), including surgery and motor vehicle accidents, catheter sites (27.4%), dressings, patches and probes (11.5%), burns and farm-related accidents (8.8%). Rhizopus spp. was most frequently isolated (43.4%), followed by Lichtheimia corymbifera (9.7%), Saksenaea vasiformis (8%), Mucor and Rhizomucor spp. (5.3% each), other species/combinations (7.2%) and unspecified isolates (21.2%). Surgery was combined with antifungals in 62.8%. Each was performed solely in 27.4% and 6.2%, respectively. Amphotericin B was used in 78% (alone in 55.8% and combined with other antifungals in 22.2%) of the cases. Overall mortality was 26.5%. In regression analysis, prematurity and haematologic malignancies/disorders were associated with increased mortality, whereas combination of antifungals and surgery with improved survival., Conclusion: Cutaneous mucormycosis mainly affects premature infants and children with haematologic malignancies/disorders. Outcome is improved when active antifungal therapy and surgery are combined., (© 2022 Wiley-VCH GmbH.)

Background: Long COVID is defined as symptoms and signs related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are present at least four weeks following acute infection. These symptoms and signs are poorly characterised but may be associated with significant morbidity. We sought to synthesise the evidence on their incidence to guide future research, policy and practice., Methods: We searched Medline and Embase for longitudinal cohort studies from January 2020 to July 2021 that investigated adults with long COVID at least four weeks after acute infection. Risk of bias was assessed using the Joanna Briggs Institute checklist for cohort studies. Random-effects meta-analyses were performed with subgroup analysis by follow-up time (4-12 vs more than 12 weeks)., Results: 19 studies were included, 13 of which included patients hospitalised with COVID-19. The total sample size was 10 643 and the follow-up time ranged from 30 to 340 days. Risk of bias was assessed as high in one study, moderate in two studies and low in the remaining 16 studies. The most common symptoms and signs seen at any time point in long COVID were fatigue (37%; 95% confidence interval (CI) = 23-55), dyspnoea (21%; 95% CI = 14-30), olfactory dysfunction (17%; 95% CI = 9-29), myalgia (12%; 95% CI = 5-25), cough (11%; 95% CI = 6-20) and gustatory dysfunction (10%; 95% CI = 7-17). High heterogeneity was seen for all meta-analyses and the presence of some funnel plot asymmetry may indicate reporting bias. No effect of follow-up time was found for any symptom or sign included in the subgroup analysis., Conclusions: We have summarised evidence from longitudinal cohort studies on the most common symptoms and signs associated with long COVID. High heterogeneity seen in the meta-analysis means pooled incidence estimates should be interpreted with caution. This heterogeneity may be attributable to studies including patients from different health care settings and countries., Competing Interests: Competing Interests: The authors completed the ICMJE Unified Competing Interest Form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland., Methods: We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020., Results: Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell's C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell's C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively., Conclusions: Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively., Competing Interests: Competing interests: JH-C reports grants from MRC, grants from Wellcome Trust, grants from NIHR, during the conduct of the study; other from ClinRisk, outside the submitted work. AS reports grants from NIHR, grants from MRC, grants from HDR UK, during the conduct of the study., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is considerable uncertainty over whether adults with asthma should be offered booster vaccines against SARS-CoV-2 and, if so, who should be prioritised for booster vaccination. We were asked by the UK's Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which adults with asthma were at an increased risk of serious COVID-19 outcomes to inform deliberations on booster COVID-19 vaccines., Methods: This national incident cohort study was done in all adults in Scotland aged 18 years and older who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). We used data from EAVE II to investigate the risk of COVID-19 hospitalisation and the composite outcome of intensive care unit (ICU) admission or death from COVID-19 among adults with asthma. A Cox proportional hazard model was used to derive adjusted hazard ratios (HRs) and 95% CIs for the association between asthma and COVID-19 hospital admission and ICU admission or death, stratified by markers of history of an asthma attack defined by either oral corticosteroid prescription (prednisolone, prednisone, and dexamethasone) in the 2 years before March 1, 2020, or hospitalisation for asthma before March 1, 2020. Analyses were adjusted for age, sex, socioeconomic status, comorbidity, previous hospitalisation, and vaccine status., Findings: Between March 1, 2020, and July 27, 2021, 561 279 (12·7%) of 4 421 663 adults in Scotland had clinician-diagnosed-and-recorded-asthma. Among adults with asthma, 39 253 (7·0%) had confirmed SARS-CoV-2 infections, of whom 4828 (12·3%) were admitted to hospital for COVID-19 (among them, an estimated 600 [12·4%] might have been due to nosocomial infections). Adults with asthma were found to be at an increased risk of COVID-19 hospital admission (adjusted HR 1·27, 95% CI 1·23-1·32) compared with those without asthma. When using oral corticosteroid prescribing in the preceding 2 years as a marker for history of an asthma attack, the adjusted HR was 1·54 (95% CI 1·46-1·61) for those with three or more prescribed courses of oral corticosteroids, 1·37 (1·26-1·48) for those with two prescribed courses, 1·30 (1·23-1·37) for those with one prescribed course, and 1·15 (1·11-1·21) for those without any courses, compared with those aged 18 years or older without asthma. Adults with asthma were found to be at an increased risk of COVID-19 ICU admission or death compared with those without asthma (adjusted HR 1·13, 95 % CI 1·05-1·22). The adjusted HR was 1·44 (95% CI 1·31-1·58) for those with three or more prescribed courses of oral corticosteroids, 1·27 (1·09-1·48) for those with two prescribed courses, 1·04 (0·93-1·16) for those with one prescribed course, and 1·06 (0·97-1·17) for those without any course, compared with adults without asthma., Interpretation: Adults with asthma who have required two or more courses of oral corticosteroids in the previous 2 years or a hospital admission for asthma before March 1, 2020, are at increased risk of both COVID-19 hospitalisation and ICU admission or death. Patients with a recent asthma attack should be considered a priority group for booster COVID-19 vaccines., Funding: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and Scottish Government., Competing Interests: Declaration of interests AS and CR are members of the Scottish Government's Chief Medical Officer COVID-19 Advisory Group. AS and CR are members of the New and Emerging Respiratory Virus Threats Advisory Group risk stratification subgroup. CR is a member of the Scientific Pandemic Influenza Group on Modelling. AS is a member of AstraZeneca's Thrombotic Thrombocytopenic Advisory Group and the Scottish Government's Standing Committee on Pandemics. AS is Director of the Asthma UK Centre for Applied Research. All aforementioned roles are unremunerated. All other authors report no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Literature findings are limited and inconsistent on the relationship between obsessive beliefs and obsessive-compulsive symptoms (OCS) and to our knowledge no data are available in pregnant population. Additionally, an interesting field that has not been adequately studied is the relationship between obsessive-compulsive personality traits and OCS while there are no corresponding studies in perinatal period. The aims of the study were to examine the relationship between OCS presented in pregnancy and obsessive beliefs considered to underlie them as well as their association with obsessive-compulsive personality traits. 30 pregnant women with OCS, regardless of their underlying diagnosis, were recruited from a University Psychiatric Hospital and privately. They completed the Mini International Neuropsychiatric Interview (MINI), the Yale-Brown Obsessive- Compulsive Scale (Y-BOCS), the Dysfunctional Beliefs Questionnaire-44 (OBQ-44), the Leyton Trait Scale and the Hospital Anxiety and Depression Scale (HADS). The main symptoms were aggression (73.3%), contamination (53.3%) obsessions and cleansing/washing (50%), checking (43.3%) compulsions. Pregnant women with obsessive-compulsive personality traits displayed symmetry/exactness obsessions (p=0.020) and cleansing/washing (p=0.011) compulsions as predominant types of OCS and greater severity of compulsions (p=0.049). The results of the logistic regression model suggest that obsessive beliefs of importance/control of thoughts and of responsibility/threat estimation predicted OCS while the belief of perfectionism/certainty did not predict any dimension of OCS. It is noteworthy that most observed relationships between obsessive beliefs and OCS remained even after controlling for variables of anxiety and depression, suggesting that obsessive beliefs have a specific relationship with OCS which is independent of other forms of psychopathology. Depressive symptoms comorbidity increased OCS severity, while in comorbidity with anxiety symptoms no difference in severity of OCS was found. Further research is needed to test our findings in larger and more diverse samples.

Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18-44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1-6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5-99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic., (© 2022. The Author(s).)

Background: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales., Methods and Findings: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates., Conclusions: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup and AstraZeneca’s COVID-19 Thrombocytopenia Taskforce; all roles are remunerated to AS or his institution. AS and SS are members of the editorial board of PLOS Medicine. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. CR is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, SPI-M, MHRA Vaccine Benefit and Risk Working Group. HRS is an advisor to the Scottish Parliament’s COVID-19 Committee. RKO is a member of the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee. DB is employed by Queen’s University Belfast, the Public Health Agency and the Department of Health (Northern Ireland). DB is a member of several Northern Ireland and UK government COVID-19 advisory boards, including the Scientific Pandemic Influenza Group on Modelling and the UK Vaccine Effectiveness Expert Panel, and has represented Northern Ireland on the UK Scientific Advisory Group for Emergencies and its subgroups. SdeL through his University holds grants from AstraZeneca, Eli-Lilly, GSK, MSD, Sanofi and Seqirus. He has been advisory board members for Astra Zeneca, Sanofi and Seqirus. MW is a member of UK government COVID-19 advisory group, SPI-M, and a member of Scottish Government COVID-19 Advisory Group. All other authors report no conflicts of interest.

Background: Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes., Methods: We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided in article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature., Results: Medline searches returned 1126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions., Conclusion: Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made, greater consistency and transparency across studies using routine data to study respiratory diseases are needed., Competing Interests: CM, HW, MM, LD, AM, CI, MA, EV, EOR, ATW, PWS have nothing to declare. JKQ reports grants from AUK-BLF, The Health Foundation, MRC, grants and personal fees from AZ, BI, GSK, Bayer, grants from Chiesi, outside the submitted work. AS reports grants from AUK-BLF and HDR UK., (© 2022 MacRae et al.)

Introduction: The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK., Methods and Analysis: We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations., Ethics and Dissemination: We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals., Competing Interests: Competing interests: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group. RAL reports grants from MRC during the conduct of the study. SJS reports grants from Wellcome Trust, during the conduct of the study; grants from National Institute of Healthcare Research HTA, grants from Tommy's Charity and grants from Chief Scientist for Scotland, outside the submitted work. SdeL is Director of the Royal College of General Practitioners Research and Surveillance Centre. He has received grant funding through his University from AstraZeneca, Eli Lilly, GSK MSD, Seqirus and Takeda. He has been members of advisory boards for AstraZeneca, Sanofi, and Seqirus. DB is jointly employed by Queen’s University Belfast, the Public Health Agency and the Department of Health (Northern Ireland), and he is currently or has been a member of COVID-19 government advisory groups, including the Scientific Advisory Group for Emergencies (SAGE), its subgroups, and the UK Vaccine Effectiveness Expert Panel. All other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blocking of inhibitory receptors and have shown promising results in preclinical models and studies on the adult population. However, paediatric malignancies present unique features, and so far, experience with these agents is limited. In the current review, we present an overview of efficacy and safety data from case reports, case series, and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents, and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)