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    Hospital admissions for viral meningitis in children in England over five decades: a population-based observational study

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    BACKGROUND:A substantial reduction in bacterial meningitis has occurred in the UK following successful implementation of immunisation programmes. Most childhood meningitis in developed countries is now caused by viruses. Long-term trends in paediatric viral meningitis in England have not previously been reported. The objective of this study is to report on epidemiological trends over time in childhood viral meningitis in England.METHODS:In this population-based observational study, we used routinely collected hospital discharge records from English National Health Service hospitals from 1968-2011 to analyse annual age-specific admission rates for viral meningitis, including specific viral aetiologies, in children younger than 15 years.FINDINGS:We analysed hospital discharge records from Jan 1, 1968, to Dec 31, 2011. Hospital admission rates for viral meningitis from Jan 1, 1968, to Dec 31, 1985, varied annually, with a mean of 13·5 admissions per 100 000 children aged less than 15 years, per year (95% CI 13·0-14·0). Admission rates declined during the late 1980s, and the mean number of admissions from 1989-2011 was 5·2 per 100 000 per year (5·1-5·3). This decrease was entirely in children aged 1-14 years. Admission rates for infants aged less than 1 year increased since 2005, to 70·0 per 100 000 (63·7-76·2) in 2011, which was driven by an increase in admission of infants aged 90 days or less. In 1968-85, the majority of cases in children were in those aged 1-14 years (22 150 [89%] of 24 920 admissions). In 2007-11, 1716 (72%) of 2382 cases were in infants. Admissions for mumps-related meningitis almost disappeared following introduction of the measles-mumps-rubella (MMR) vaccine in 1988. Admissions with a specified viral aetiology have increased since 2000.INTERPRETATION:Trends in viral meningitis admissions have changed substantially over the past 50 years, and probably reflect the impact of the MMR vaccine programme and the use of more sensitive diagnostic techniques

    Intravenous immunoglobulin for the treatment of childhood encephalitis

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    Background: Encephalitis is a syndrome of neurological dysfunction due to inflammation of the brain parenchyma, caused by an infection or an exaggerated host immune response, or both. Attenuation of brain inflammation through modulation of the immune response could improve patient outcomes. Biological agents such as immunoglobulin that have both anti-inflammatory and immunomodulatory properties may therefore be useful as adjunctive therapies for people with encephalitis.Objectives: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) as add-on treatment for children with encephalitis.Search methods: The Cochrane Multiple Sclerosis and Rare Diseases of the CNS group's Information Specialist searched the following databases up to 30 September 2016: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and the WHO ICTRP Search Portal. In addition, two review authors searched Science Citation Index Expanded (SCI-EXPANDED) &amp; Conference Proceedings Citation Index - Science (CPCI-S) (Web of Science Core Collection, Thomson Reuters) (1945 to January 2016), Global Health Library (Virtual Health Library), and Database of Abstracts of Reviews of Effects (DARE).Selection criteria: Randomised controlled trials (RCTs) comparing IVIG in addition to standard care versus standard care alone or placebo.Data collection and analysis: Two review authors independently selected articles for inclusion, extracted relevant data, and assessed quality of trials. We resolved disagreements by discussion among the review authors. Where possible, we contacted authors of included studies for additional information. We presented results as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI).Main results: The search identified three RCTs with 138 participants. All three trials included only children with viral encephalitis, one of these included only children with Japanese encephalitis, a specific form of viral encephalitis. Only the trial of Japanese encephalitis (22 children) contributed to the primary outcome of this review and follow-up in that study was for three to six months after hospital discharge. There was no follow-up of participants in the other two studies. We identified one ongoing trial.For the primary outcomes, the results showed no significant difference between IVIG and placebo when used in the treatment of children with Japanese encephalitis: significant disability (RR 0.75, 95% CI 0.22 to 2.60; P = 0.65) and serious adverse events (RR 1.00, 95% CI 0.07 to 14.05; P = 1.00).For the secondary outcomes, the study of Japanese encephalitis showed no significant difference between IVIG and placebo when assessing significant disability at hospital discharge (RR 1.00, 95% CI 0.60 to 1.67). There was no significant difference (P = 0.53) in Glasgow Coma Score at discharge between IVIG (median score 14; range 3 to 15) and placebo (median 14 score; range 7 to 15) in the Japanese encephalitis study. The median length of hospital stay in the Japanese encephalitis study was similar for IVIG-treated (median 13 days; range 9 to 21) and placebo-treated (median 12 days; range 6 to 18) children (P = 0.59).Pooled analysis of the results of the other two studies resulted in a significantly lower mean length of hospital stay (MD -4.54 days, 95% CI -7.47 to -1.61; P = 0.002), time to resolution of fever (MD -0.97 days, 95% CI -1.25 to -0.69; P &lt; 0.00001), time to stop spasms (MD -1.49 days, 95% CI -1.97 to -1.01; P &lt; 0.00001), time to regain consciousness (MD -1.10 days, 95% CI -1.48 to -0.72; P &lt; 0.00001), and time to resolution of neuropathic symptoms (MD -3.20 days, 95% CI -3.34 to -3.06; P &lt; 0.00001) in favour of IVIG when compared with standard care.None of the included studies reported other outcomes of interest in this review including need for invasive ventilation, duration of invasive ventilation, cognitive impairment, poor adaptive functioning, quality of life, number of seizures, and new diagnosis of epilepsy. The quality of evidence was very low for all outcomes of this review.Authors' conclusions: The findings suggest a clinical benefit of adjunctive IVIG treatment for children with viral encephalitis for some clinical measures (i.e. mean length of hospital stay, time (days) to stop spasms, time to regain consciousness, and time to resolution of neuropathic symptoms and fever. For children with Japanese encephalitis, IVIG had a similar effect to placebo when assessing significant disability and serious adverse events.Despite these findings, the risk of bias in the included studies and quality of the evidence make it impossible to reach any firm conclusions on the efficacy and safety of IVIG as add-on treatment for children with encephalitis. Furthermore, the included studies involved only children with viral encephalitis, therefore findings of this review cannot be generalised to all forms of encephalitis. Future well-designed RCTs are needed to assess the efficacy and safety of IVIG in the management of children with all forms of encephalitis. There is a need for internationally agreed core outcome measures for clinical trials in childhood encephalitis.</p

    Problem-solving in clinical practice: persisting respiratory distress in a premature infant

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    The deterioration of a previously stable preterm infant is a common scenario on the neonatal unit. The the most common bacterial causes of deterioration are nosocomial infections, such as coagulase-negative Staphylococcus and Staphylococcus aureus. Non-infective conditions such as pulmonary haemorrhage, anaemia of prematurity and necrotising enterocolitis may also cause preterm infants to deteriorate. This case chronicles the unusual diagnostic journey of an infant born at 27+1 weeks who deteriorated at 26 days of life and did not respond to antimicrobial therapy as anticipated.</p

    30-year trends in admission rates for encephalitis in children in England and effect of improved diagnostics and measles-mumps-rubella vaccination:a population-based observational study

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    Background Encephalitis is a serious neurological disorder, yet data on admission rates for all-cause childhood encephalitis in England are scarce. We aimed to estimate admission rates for childhood encephalitis in England over 33 years (1979–2011), to describe trends in admission rates, and to observe how these rates have varied with the introduction of vaccines and improved diagnostics. Methods We did a retrospective analysis of hospital admission statistics for encephalitis for individuals aged 0–19 years using national data from the Hospital Inpatient Enquiry (HIPE, 1979–85) and Hospital Episode Statistics (HES, 1990–2011). We analysed annual age-specific and age-standardised admission rates in single calendar years and admission rate trends for specified aetiologies in relation to introduction of PCR testing and measles-mumps-rubella (MMR) vaccination. We compared admission rates between the two International Classification of Diseases (ICD) periods, ICD9 (1979–94) and ICD10 (1995–2011). Findings We found 16 571 encephalitis hospital admissions in the period 1979–2011, with a mean hospital admission rate of 5·97 per 100 000 per year (95% CI 5·52–6·41). Hospital admission rates declined from 1979 to 1994 (ICD9; annual percentage change [APC] −3·30%; 95% CI −2·88 to −3·66; p&lt;0·0001) and increased between 1995 and 2011 (ICD10; APC 3·30%; 2·75–3·85; p&lt;0·0001). Admissions for measles decreased by 97% (from 0·32 to 0·009) and admissions for mumps encephalitis decreased by 98% (from 0·60 to 0·01) after the introduction of the two-dose MMR vaccine. Hospital admission rates for encephalitis of unknown aetiology have increased by 37% since the introduction of PCR testing. Interpretation Hospital admission rates for all-cause childhood encephalitis in England are increasing. Admissions for measles and mumps encephalitis have decreased substantially. The numbers of encephalitis admissions without a specific diagnosis are increasing despite availability of PCR testing, indicating the need for strategies to improve aetiological diagnosis in children with encephalitis

    A population based observational study of childhood encephalitis in children admitted to pediatric intensive care units in England and Wales

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    BACKGROUND: Encephalitis is a serious neurologic condition which can result in admission to intensive care. Yet, there are no studies on pediatric intensive care unit (PICU) admission rates and usage of intensive care resources by children with encephalitis in England and Wales. The objectives of this study were to (i) define the PICU incidence and mortality rates for childhood encephalitis, (ii) describe usage of intensive care resources by children with encephalitis admitted to PICU, and (iii) explore the associated cost from PICU encephalitis admissions.METHODS: Retrospective analysis of anonymized data for 1031 children (0-17 years) with encephalitis admitted (January 2003 to December 2013) to PICU in England and Wales.RESULTS: The PICU encephalitis incidence was 0.79/100,000 population/year (95%CI 0.74-0.84), which gives an annual total of 214 bed days of intensive care occupancy for children admitted with encephalitis and an estimated annual PICU bed cost of £414,230 (IQR 198,111-882,495) for this cohort. PICU encephalitis admissions increased during the study period (annual percentage change = 4.5%, 95%CI 2.43%-6.50%, p=&lt;0.0001). In total, 808/1024 (78.9%) received invasive ventilation while 216/983 (22.0%) and 50/890 (5.6%) cases received vasoactive treatment and renal support, respectively. There were 87 deaths (8.4%), giving a PICU encephalitis mortality rate of 0.07 /100,000 population (0-17 years)/year (95%CI 0.05-0.08).CONCLUSIONS: These data suggest that encephalitis places a significant burden to the healthcare service. More work is needed to improve outcomes for children with encephalitis.</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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