Publications by authors named "Tisham De"

Objective: To investigate a dose-response relationship between the magnitude of decrease in pediatric respiratory tract infections (RTI) during the 2020 implementation of non-pharmaceutical interventions (NPI) and the rise thereafter during NPI lifting.

Study Design: We conducted an interrupted, time-series analysis, based on a multinational surveillance system. All patients <16 years of age coming to medical attention with various symptoms and signs of RTI at 25 pediatric emergency departments from 13 European countries between January 2018 and June 2022 were included.

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Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls.

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  • Differentiating between self-resolving viral infections and bacterial infections in children with fever is challenging and can lead to improper use of antibiotics; this study aims to identify host protein biomarkers that could help distinguish between these infections.
  • The research used a multi-cohort approach and high-dimensional proteomic datasets from various European studies to shortlist potential protein biomarkers by performing several analyses and tests on collected samples.
  • A sparse protein signature was successfully identified, which distinguishes between bacterial and viral infections, and its effectiveness was validated through Luminex assays and disease risk score calculations.
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  • Antibiotic overprescription in pediatric emergency departments (EDs) contributes to antimicrobial resistance, prompting a study on empiric antibiotic use in European EDs for febrile children.
  • Out of 2130 febrile cases studied, 72.7% were classified as bacterial and 27.3% as viral, with 85.1% of bacterial and 46.3% of viral cases receiving empiric systemic antibiotics within the first two days.
  • A large portion of patients with viral infections were still given antibiotics, typically from the WHO's "Watch" category, highlighting the need for better diagnostic methods in EDs to accurately distinguish between bacterial and viral infections.
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  • The study aimed to validate and update the Feverkids tool, a clinical prediction model designed to help differentiate between bacterial pneumonia, serious bacterial infections (SBIs), and non-SBI causes of fever in immunocompromised children.
  • Conducted in 15 hospitals across nine European countries, the study involved observational data from febrile immunocompromised children aged 0-18 years.
  • Results showed improved accuracy in predicting bacterial pneumonia and SBIs after model updates, indicating effective thresholds that can help minimize unnecessary medical interventions and antibiotic use.
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Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.

Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data.

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Background: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.

Methods: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138).

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Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.

Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort.

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Background: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis.

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To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the 'Biomarker Validation in HR patients' database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations.

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  • The objective of the study was to evaluate how epidemics and pandemics affect the use of pediatric emergency care services to inform health policy.
  • A systematic review of 131 articles was conducted, finding that most studies (80%) focused on COVID-19, which resulted in a significant 63.86% reduction in pediatric emergency department visits, although other epidemics showed varied effects.
  • The findings suggest that public fear of disease significantly influences how people seek emergency care, and policymakers need to consider this anxiety while also recognizing gaps in reported data on the impact of epidemics on pediatric care usage.
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Background: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses.

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  • The study evaluated how pediatric emergency departments (PEDs) in Europe adapted their services during the first wave of COVID-19, focusing on changes in healthcare pathways.
  • About 97% of the surveyed 39 PEDs across 17 countries remained open and operational, though 68% saw a decrease in the capacity of short-stay units.
  • Despite the pandemic, there was minimal change in the availability of pediatric consultant services, and no clear relationship was found between service changes and peak COVID-19 case rates in the areas surveyed.
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Here, with the example of common copy number variation (CNV) in the gene, we present an important piece of work in the field of CNV detection, that is, CNV association with complex human traits such as H NMR metabolomic phenotypes and an example of functional characterization of CNVs among human induced pluripotent stem cells (HipSci). We report exon 11 (ENSE00003720745) as a pleiotropic locus associated with metabolomic regulation and show that its biology is associated with several metabolic diseases such as type 2 diabetes (T2D) and cancer. Our results further demonstrate the power of multivariate association models over univariate methods and define metabolomic signatures for variants in .

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The limited diagnostic accuracy of biomarkers in children at risk of a serious bacterial infection (SBI) might be due to the imperfect reference standard of SBI. We aimed to evaluate the diagnostic performance of a new classification algorithm for biomarker discovery in children at risk of SBI. We used data from five previously published, prospective observational biomarker discovery studies, which included patients aged 0- <16 years: the Alder Hey emergency department ( = 1,120), Alder Hey pediatric intensive care unit ( = 355), Erasmus emergency department ( = 1,993), Maasstad emergency department ( = 714) and St.

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Background: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.

Methods: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone.

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COSMIC, the Catalogue of Somatic Mutations in Cancer (http://cancer.sanger.ac.

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Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes.

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Germ-line genetic control of gene expression occurs via expression quantitative trait loci (eQTLs). We present a large, exon-specific eQTL data set covering ten human brain regions. We found that cis-eQTL signals (within 1 Mb of their target gene) were numerous, and many acted heterogeneously among regions and exons.

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We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a minimum of 12 months in accordance with the consensus statement from the International League Against Epilepsy (ILAE).

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The mechanisms underlying coronary microvascular remodeling and dysfunction, which are critical determinants of abnormal myocardial blood flow regulation in human hypertension, are poorly understood. The spontaneously hypertensive rat (SHR) exhibits many features of human hypertensive cardiomyopathy. We demonstrate that remodeling of intramural coronary arterioles is apparent in the SHR already at 4 weeks of age, i.

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