Emotional Well-Being in Children with New-Onset Epilepsy

Research suggests increased risk for adverse psychosocial outcomes and poor health-related quality of life and emotional well-being (EWB) in children with epilepsy compared to their healthy peers. The factors associated with poor EWB and the course of EWB in these children remains unclear. The objectives of this study were to: investigate the relationship between epilepsy-related and family factors and children’s EWB two years after the diagnosis of epilepsy; identify the average group trajectory of EWB in children with newly-diagnosed epilepsy over the first two years; and investigate whether we can identify subgroups of children with epilepsy that can be better represented with yet unidentified unique trajectories to describe their course of EWB, rather than using a single homogeneous group trajectory to represent all children. Data came from a multi-centre prospective cohort study of children with newly-diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n=373). EWB was measured using the Quality of Life in Childhood Epilepsy Questionnaire. Multiple regression assessed the relationship between epilepsy-related factors and EWB and tested possible mediation or moderation effects of family factors. Latent growth modeling and multinomial logistic regression was used to identify trajectories of EWB, the factors associated with each trajectory, and predictors of group membership to a particular trajectory. Behavioural problems, family functioning, family demands, and family resources were associated with poor EWB two-years post-diagnosis. Parental depressive symptoms were partially mediated by family functioning and by family demands. Family resources played a dual mediator/moderator role, moderating the relationship between severity of epilepsy and EWB. Two linear trajectories were identified, with the same set of factors associated with baseline EWB for both trajectories, but factors differed in their association with EWB across time for the two trajectories. The level of severity of epilepsy and family resources predicted a child’s membership to a particular trajectory. Poor EWB in children with epilepsy is associated with several epilepsy-related and family factors. After a diagnosis of epilepsy, family factors appear to be the most important influences on changes in EWB over time so efforts to strengthen the family environment may warrant attention

Measurement equivalence of the newly developed Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55)

Summary Objective The aim of this study was to examine measurement equivalence of the newly developed Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) across age, sex, and time in a representative sample of children with newly diagnosed epilepsy. Methods Data come from 373 children enrolled in the Health-related Quality of Life in Children with Epilepsy Study (HERQULES), a multisite prospective cohort study. Measurement equivalence was examined using a multiple-group confirmatory factor analysis framework, whereby increasingly stringent parameter constraints are imposed on the model. Comparison groups were stratified based on age (4-7 years vs. 8-12 years), sex (male vs. female), and time (measurement of health-related quality of life at diagnosis vs. 24 months later). Results The QOLCE-55 demonstrated measurement equivalence at the level of strict invariance for each model tested - age: χ2 (3,123) = 4,097.3, p \u3c 0.001; Comparative Fit Index (CFI) = 0.968; Root Mean Square Error of Approximation (RMSEA) = 0.042 (0.038, 0.045); sex: χ2 (3,124) = 4,188.3, p \u3c 0.001; CFI = 0.964; RMSEA = 0.044 (0.040, 0.047); and time: χ2 (3,121) = 5,185.0, p \u3c 0.001; CFI = 0.965; RMSEA = 0.046 (0.043, 0.048). Significance These findings suggest that items comprising the QOLCE-55 are perceived similarly among groups stratified by age, sex, and time and provide further evidence supporting the validity of the scale in children with epilepsy. Health professionals and researchers should be confident that group comparisons made using the QOLCE-55 are unbiased and that any group differences detected are meaningful; that is, not related to differences in the interpretation of items by informants. Future research replicating these findings is encouraged

Emotional well-being in children with epilepsy: Family factors as mediators and moderators

Objective: Our objective was to examine the relationships of factors associated with children\u27s emotional well-being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors. Methods: Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well-being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). The relationships between clinical factors, family factors, and emotional well-being were assessed using multiple regression analyses. Results: Family functioning, family stress, and repertoire of resources that the families had to adapt to stressful events were significantly associated with poor emotional well-being 2 years after diagnosis (p \u3c 0.05) in the multivariable analysis. The effect of parental depressive symptoms was partially mediated by family functioning and family stress (p \u3c 0.01 and p = 0.02, respectively). Family resources acted as a moderator in the relationship between severity of epilepsy and emotional well-being (p \u3c 0.05). Significance: Based on our findings, efforts to strengthen the family environment may warrant attention. We suggest that clinicians take a family centered care approach by including families in treatment planning. Family centered care has been shown to improve family well-being and coping and in turn may reduce the impact of clinical factors on emotional well-being to improve long-term health-related quality of life

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society