Understanding parental perspectives on outcomes following paediatric encephalitis: A qualitative study

Background Encephalitis, characterised as inflammation of the brain tissue, is an important cause of acquired brain injury in children. Objective clinical outcomes vary significantly between affected patients, however they do not always correlate with quality of life as reported by parents. The aim of this study was to explore how parents experience and interpret outcomes in relation to their child who has been affected by encephalitis. Methods Data were derived from in-depth, semi-structured interviews, with 15 parents of 12 children and young people affected by encephalitis. Paediatric cases were identified from the retrospective arm of the research programme ‘ENCEPH-UK-Understanding and Improving the Outcome of Encephalitis’, and from the prospective UK childhood meningitis and encephalitis cohort study (UK-ChiMES, 2012 to 2016). Data were analysed thematically. Results Parents’ perspectives on important outcomes for their child and family changed during the different stages of the encephalitis illness trajectory: from acute illness, recovery and rehabilitation, then reintegration into everyday life. Parents’ understanding of their children’s overall outcome was informed by their own experiences, involving comparisons with other children and reflections on their child’s problems before, during and after the acute illness. Conclusion Outcomes in paediatric encephalitis need to be understood in terms of the context of the patient and family experience as well as the timeframe of recovery. The research highlights the need to include more patient, parent and/or carer reported outcome measures during patient assessment, and that assessment should be repeated during recovery as family concerns change. In the longer term, these parameters could be included in clinical and rehabilitation practice to further support child recovery

Regulatory T cell profiles in patients with N-methyl-ᴅ-aspartate receptor-antibody encephalitis

Purpose Purpose Regulatory T cells (Tregs) have been implicated in the pathogenesis of several autoimmune disorders and used in adoptive cell transfer therapies. Neither have been explored in patients with autoimmune encephalitis where treated patient outcomes remain suboptimal with frequent relapses. Here, to identify new treatment strategies for autoimmune encephalitis, we sought to evaluate the proportion of circulating Tregs and Treg subpopulations in peripheral blood of patients with N-methyl-ᴅ-aspartate receptor-antibody encephalitis (NMDAR-Ab-E) and compared this with healthy controls. Methods We compared the phenotype of peripheral blood Tregs in four adult NMDAR-Ab-E patients and four age- and sex-matched healthy controls using an 11-color flow cytometry assay panel for characterization of Tregs (CD4+ CD25+ FoxP3+) cells into naïve (chemokine receptor [CCR] 7+ CD45RA+), central memory (CCR7+ CD45RA–), and effector memory (CCR7– CD45RA–) cells. We also examined and compared the expression of the CCR6 by circulating Tregs and the respective Treg subpopulations between the study groups. Results The proportion of circulating Tregs was similar between patients with NMDAR-Ab-E and healthy controls but the proportion of naïve Tregs was lower in NMDAR-Ab-E patients (p = 0.0026). Additionally, the frequency of circulating effector memory Tregs was higher, and the proportion of circulating effector memory Tregs expressing CCR6 was lower, in NMDAR-Ab-E patients compared with healthy controls (p = 0.0026). Conclusion Altered Treg homeostasis may be a feature of patients with NMDAR-Ab-E. Future studies with larger samples are warranted to validate these findings

Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome?

Immune signatures measured at baseline and immediately prior to vaccination may predict the immune response to vaccination. Such pre-vaccine assessment might allow not only population-based, but also more personalized vaccination strategies ('precision vaccination'). If baseline immune signatures are predictive, the underlying mechanism they reflect may also determine vaccination outcome. Thus, baseline signatures might contribute to identifying interventional targets to be modulated prior to vaccination in order to improve vaccination responses. This concept has the potential to transform vaccination strategies and usher in a new approach to improve global health

Death within 8 years after childhood convulsive status epilepticus:a population-based study

The risk of long-term mortality and its predictors following convulsive status epilepticus in childhood are uncertain. We report mortality within 8 years after an episode of convulsive status epilepticus, and investigate its predictors from a paediatric, prospective, population-based study from north London, UK. In the current study, we followed-up a cohort previously ascertained during a surveillance study of convulsive status epilepticus in childhood. After determining the survival status of the cohort members, we defined cause of death as that listed on their death certificates. We estimated a standardized mortality ratio to compare mortality in our cohort with that expected in the reference population. Multivariable Cox regression analysis was used to investigate any association between the clinical and demographic factors at the time of status epilepticus and subsequent risk of death. The overall case fatality was 11% (95% confidence interval 7.5–16.2%); seven children died within 30 days of their episode of convulsive status epilepticus and 16 during follow-up. The overall mortality in our cohort was 46 times greater than expected in the reference population, and was predominantly due to higher mortality in children who had pre-existing clinically significant neurological impairments when they had their acute episode of convulsive status epilepticus. Children without prior neurological impairment who survived their acute episode of convulsive status epilepticus were not at a significantly increased risk of death during follow-up. There were no deaths in children following prolonged febrile convulsions and idiopathic convulsive status epilepticus. A quarter of deaths during follow-up were associated with intractable seizures/convulsive status epilepticus, and the rest died as a complication of their underlying medical condition. On regression analysis, presence of clinically significant neurological impairments prior to convulsive status epilepticus was the only independent risk factor for mortality. In conclusion, there is a high risk of death within 8 years following childhood convulsive status epilepticus but most deaths are not seizure related. Presence of pre-existing clinically significant neurological impairments at the time of convulsive status epilepticus is the main risk factor for mortality within 8 years after the acute episode. The attributable role of convulsive status epilepticus on mortality remains uncertain, but appears less than is generally perceived

A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

OBJECTIVES: To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. METHODS: The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. RESULTS: Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. CONCLUSIONS: This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis

Auto-titrating continuous positive airway pressure for patients with acute transient ischemic attack: a randomized feasibility trial

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. METHODS: All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as >or=4 hours per night for >or=75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. RESULTS: We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%;P=0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%;some, 5%;acceptable adherence 0% (P=0.08). CONCLUSIONS: Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA

Exchanging screen for non-screen sitting time or physical activity might attenuate depression and anxiety: A cross-sectional isotemporal analysis during early pandemics in South America

Objectives: To examine the theoretical substitutions of screen exposure, non-screen sitting time, moderate and vigorous physical activity with depressive and anxiety symptoms in South American adults during the COVID-19 pandemic. Design: A cross-sectional study during the first months of the COVID-19 pandemic with data from 1981 adults from Chile, Argentina, and Brazil. Methods: Depressive and anxiety symptoms were assessed using the Beck Depression and Anxiety Inventories. Participants also reported physical activity, sitting time, screen exposure, sociodemographic, and tobacco use data. Isotemporal substitution models were created using multivariable linear regression methods. Results: Vigorous physical activity, moderate physical activity, and screen exposure were independently associated with depression and anxiety symptoms. In adjusted isotemporal substitution models, replacing 10 min/day of either screen exposure or non-screen sitting time with any intensity of physical activity was associated with lower levels of depressive symptoms. Improvements in anxiety symptoms were found when reallocating either screen exposure or non-screen sitting time to moderate physical activity. Furthermore, replacing 10 min/day of screen exposure with non-screen sitting time was beneficially associated with anxiety (B = − 0.033; 95 % CI = − 0.059, − 0.006) and depression (B = − 0.026; 95 % CI = − 0.050, − 0.002). Conclusions: Replacement of screen exposure with any intensity of physical activity or non-screen sitting time could improve mental health symptoms. Strategies aiming to reduce depressive and anxiety symptoms highlight physical activity promotion. However, future interventions should explore specific sedentary behaviors as some will relate positively while others negatively.Fil: Sadarangani, Kabir P.. Universidad Autónoma de Chile; Chile. Universidad Diego Portales; ChileFil: Schuch, Felipe Barreto. Universidade Federal de Santa Maria; Brasil. Universidad Autónoma de Chile; ChileFil: de Roia, Gabriela Fernanda. Universidad de Flores. Laboratorio de Estudios en Actividad Física;Fil: Martínez Gomez, David. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; España. Consortium for Biomedical Research in Epidemiology and Public Health; EspañaFil: Chávez, Róbinson. Universidad Andrés Bello; ChileFil: Lobo, Pablo Roberto. Universidad de Flores. Laboratorio de Estudios en Actividad Física;Fil: Cristi Montero, Carlos. Pontificia Universidad Católica de Valparaíso; ChileFil: Werneck, André O.. Universidade de Sao Paulo; BrasilFil: Alzahrani, Hosam. Taif University; Arabia SauditaFil: Ferrari, Gerson. Universidad de Santiago de Chile; ChileFil: Ibañez, Agustin Mariano. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Trinity College Dublin; Irlanda. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Silva, Danilo R.. Universidade Federal de Sergipe; Brasil. Universidad Pablo de Olavide; EspañaFil: Von Oetinger, Astrid. Universidad Diego Portales; Chile. Universidad Mayor; ChileFil: Matias, Thiago S.. Universidade Federal de Santa Catarina; BrasilFil: Grabovac, Igor. Universidad de Viena; AustriaFil: Meyer, Jacob. Iowa State University; Estados Unido

Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore.

To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings

Assessment of infant position and timing of stylet removal to improve lumbar puncture success in neonates (NeoCLEAR): an open-label, 2 × 2 factorial, randomised, controlled trial

Background Newborn infants are the highest-risk age group for bacterial meningitis. Lumbar punctures are therefore frequently performed in neonates, but success rates are low (50-60%). In Neonatal Champagne Lumbar punctures Every time-A Randomised Controlled Trial (NeoCLEAR), we sought to optimise infant lumbar puncture by evaluating two modifications to traditional technique: sitting position versus lying down and early stylet removal (stylet removal after transecting the subcutaneous tissue) versus late stylet removal