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      Seasonal distribution of febrile seizure and the relationship with respiratory and enteric viruses in Korean children based on nationwide registry data

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          Highlights

          • Febrile seizures were reported to be associated with seasonal viral epidemics.

          • The seasonal distribution of febrile seizures was high from late spring to summer.

          • Influenza virus and enterovirus was most frequently associated with febrile seizure.

          Abstract

          Purpose

          The seasonal distribution patterns of febrile seizures and of respiratory and enteric viral pathogens are similar. In this study, we analyzed trends in febrile seizures and viral infection in Korean children, using big data from the Korean Health Insurance Review and Assessment Service (HIRA).

          Methods

          We analyzed children younger than 6 years who visited the hospital and were diagnosed with febrile seizures from 2009 to 2016, using medical records in the HIRA database. A total of 666,136 medical records of children with a main or subdiagnosis of febrile seizure from 2008 to 2016 were included. Of these records, patients younger than 1 month and records before 2009 were excluded. Finally, 558,130 records were extracted.

          Results

          The medical records included 315,774 male children and 242,356 (43.4%) female children, with a mean age of 2.31 ± 1.31 years. The annual incidence of febrile seizure was 25.4 per 1000 person-years (27.9 for boys and 22.7 for girls). The ratio of male to female children was 1.30: 1, and records of 1-year-old children comprised the highest proportion (n = 210,400, 33.70%). The total monthly number of patients was highest in May (n = 64,969, 11.6%), and peaks were formed from April to July. The fewest patients were seen in October (n = 34,424, 6.17%). The most common viral pathogens were influenza in April and enterovirus during May–July.

          Conclusion

          The seasonal distribution of febrile seizures was high from late spring to summer, and influenza virus and enterovirus were most frequently associated.

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          Most cited references28

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          Respiratory Syncytial Virus—A Comprehensive Review

          Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although there have been extensive studies of epidemiology, clinical manifestations, diagnostic techniques, animal models and the immunobiology of infection, there is not yet a convincing and safe vaccine available. The major histopathologic characteristics of RSV infection are acute bronchiolitis, mucosal and submucosal edema, and luminal occlusion by cellular debris of sloughed epithelial cells mixed with macrophages, strands of fibrin, and some mucin. There is a single RSV serotype with two major antigenic subgroups, A and B. Strains of both subtypes often co-circulate, but usually one subtype predominates. In temperate climates, RSV infections reflect a distinct seasonality with onset in late fall or early winter. It is believed that most children will experience at least one RSV infection by the age of 2 years. There are several key animal models of RSV. These include a model in mice and, more importantly, a bovine model; the latter reflects distinct similarity to the human disease. Importantly, the prevalence of asthma is significantly higher amongst children who are hospitalized with RSV in infancy or early childhood. However, there have been only limited investigations of candidate genes that have the potential to explain this increase in susceptibility. An atopic predisposition appears to predispose to subsequent development of asthma and it is likely that subsequent development of asthma is secondary to the pathogenic inflammatory response involving cytokines, chemokines and their cognate receptors. Numerous approaches to the development of RSV vaccines are being evaluated, as are the use of newer antiviral agents to mitigate disease. There is also significant attention being placed on the potential impact of co-infection and defining the natural history of RSV. Clearly, more research is required to define the relationships between RSV bronchiolitis, other viral induced inflammatory responses, and asthma.
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            Influenza A infection is an important cause of febrile seizures.

            To compare the incidence of febrile seizures in children hospitalized for influenza A infection with parainfluenza and adenovirus infection and to examine the hypothesis that children hospitalized for influenza A (variant Sydney/H3N2) during the 1998 season in Hong Kong had more frequent and refractory seizures when compared with other respiratory viruses, including the A/Wuhan H3N2 variant that was present in the previous year. Medical records of children between 6 months and 5 years of age admitted for influenza A infection in 1998 were reviewed. For comparison, records of children of the same age group with influenza A infection in 1997, and with parainfluenza and adenovirus infections between 1996 and 1998 were reviewed. Children who were afebrile or who had an underlying neurologic disorder were excluded. Of children hospitalized for influenza A in 1998 and 1997, 54/272 (19.9%) and 27/144 (18.8%) had febrile seizures, respectively. The overall incidence of febrile seizures associated with influenza A (19.5%) was higher than that in children hospitalized for parainfluenza (18/148; 12.2%) and adenovirus (18/199; 9%) infection, respectively. In children who had febrile seizures, repeated seizures were more commonly associated with influenza A infection than with parainfluenza or adenovirus infection (23/81 [28%] vs 3/36 [8.3%], odds ratio [OR] 4.3, 95% confidence interval: 1.2 to 15.4). Alternatively, children with influenza A infection had a higher incidence (23/416, 5.5%) of multiple seizures during the same illness than those with adenovirus or parainfluenza infection (3/347, 0.86%; OR 6.7, 95% confidence interval: 2.0-22.5.) The increased incidence of febrile seizures associated with influenza A was not attributable to differences in age, gender, or family history of febrile seizure. Multivariate analysis, adjusted for peak temperature and duration of fever, showed that hospitalized children infected with infection A had a higher risk of febrile seizures than those who were infected with parainfluenza or adenovirus (OR 1.97). Influenza A infection was a significant cause of febrile seizure admissions. Of 250 and 249 children admitted to Queen Mary Hospital for febrile seizures in 1997 and 1998, respectively, influenza A infection accounted for 27 (10.8%) admissions in 1997 and 54 (21.7%) in 1998. During months of peak influenza activity, it accounted for up to 35% to 44% of febrile seizure admissions. In contrast, parainfluenza, adenovirus, respiratory syncytial virus, and influenza B had a smaller contribution to hospitalizations for febrile seizures, together accounting for only 25/250 (10%) admissions in 1997 and 16/249 (6.4%) in 1998. The influenza A Sydney variant (H3N2) was not associated with an increased risk of febrile seizures when compared with the previous influenza A Wuhan variant (H3N2) or H1N1 viruses. However, in hospitalized children, influenza A is associated with a higher incidence of febrile seizures and of repeated seizures in the same febrile episode than are adenovirus or parainfluenza infections. The pathogenesis of these observations warrants additional studies. Complex febrile seizures, particularly multiple febrile seizures at the time of presentation, have been thought to carry an adverse long-term prognosis because of its association with a higher incidence of epilepsy. Repeated febrile seizures alone, particularly if associated with influenza A infection, may not be as worrisome as children with complex febrile seizures because of other causes, which requires additional investigation. This may subsequently have an impact on reducing the burden of evaluation in a subset of children with complex febrile seizures.
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              Introduction: health of the health care system in Korea.

              This study is a mega evaluation of Korea's health care system as developed thus far. It aims to review the historical context in which this system was developed and the political stage and motivation for such development. It will highlight unique features of the system and some comparative analysis with other developed nations. Then it will introduce selective, specific areas and aspects of the health care system, service delivery, and practices. It will suggest its implications for future direction.
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                Author and article information

                Contributors
                Journal
                Seizure
                Seizure
                Seizure
                British Epilepsy Association. Published by Elsevier Ltd.
                1059-1311
                1532-2688
                18 October 2019
                December 2019
                18 October 2019
                : 73
                : 9-13
                Affiliations
                [0005]Department of Pediatrics, Chung-Ang University Hospital, 102, Heukseok-ro, Dongjak-gu, Seoul, South Korea
                Author notes
                [* ]Corresponding author. kidbrain@ 123456cau.ac.kr
                Article
                S1059-1311(18)30794-5
                10.1016/j.seizure.2019.10.008
                7111037
                31675516
                b5be6481-d974-444b-a926-475baafdc4af
                © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 6 December 2018
                : 17 July 2019
                : 9 October 2019
                Categories
                Article

                hira, korean health insurance review and assessment service,nhi, national health insurance,rsv, respiratory syncytial virus,febrile seizure,seasonal distribution,virus infection

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