Impact of prematurity on LINE-1 promoter methylation.

Aim: Promoter methylation of LINE-1 may be affected by prematurity, but there is little evidence in the literature.Materials & methods: Blood from premature and full-term neonates on days 0, 5, 30 and 90 was analyzed for DNA methylation percentage in a promoter region of the LINE-1, after bisulfite conversion and pyrosequencing.Results: Premature infants, as a whole, showed significantly lower methylation percentage at birth, but this difference diminished over time. However, the subgroup of extremely premature (<28 weeks gestational age) had higher methylation percentages, similar to full-term newborns.Conclusion: This research underscores the critical role of prematurity on the methylation pattern of LINE-1. These findings underline the complexity of epigenetic regulation in prematurity and emphasize the need for further studies.

Premature birth can have significant effects on a baby's development and long-term health. This study investigates how being born prematurely affects a process called DNA methylation, which can influence how genes are turned on or off. Specifically, we examined the LINE-1 promoter, a frequently occurring region of DNA known for its role in regulating gene activity.We collected blood samples from both premature and full-term newborns at birth and at several points in the early months of life. Our findings showed that premature babies have lower levels of LINE-1 promoter methylation at birth compared with full-term babies. These differences in methylation could possibly affect the babies' development and health as they grow.Our research highlights the need for continued study in this area to explore how these epigenetic changes impact long-term health and to develop strategies to mitigate these effects.

High-fidelity simulation versus case-based discussion for training undergraduate medical students in pediatric emergencies: a quasi-experimental study

Abstract Objective: To evaluate the effect of high-fidelity simulation of pediatric emergencies compared to case-based discussion on the development of self-confidence, theoretical knowledge, clinical reasoning, communication, attitude, and leadership in undergraduate medical students. Methods: 33 medical students were allocated to two teaching methods: high-fidelity simulation (HFS, n = 18) or case-based discussion (CBD, n = 15). Self-confidence and knowledge tests were applied before and after the interventions and the effect of HFS on both outcomes was estimated with mixed-effect models. An Objective Structured Clinical Examination activity was conducted after the interventions, while two independent raters used specific simulation checklists to assess clinical reasoning, communication, attitude, and leadership. The effect of HFS on these outcomes was estimated with linear and logistic regressions. The effect size was estimated with the Hedge'sg. Results: Both groups had an increase in self-confidence (HFS 59.1 × 93.6, p < 0.001; CDB 50.5 × 88.2, p < 0.001) and knowledge scores over time (HFS 45.1 × 63.2, p = 0.001; CDB 43.5 × 56.7, p-value < 0.01), but no difference was observed between groups (group*time effect in the mixed effect models adjusted for the student ranking) for both tests (p = 0.6565 and p = 0.3331, respectively). The simulation checklist scores of the HFS group were higher than those of the CBD group, with large effect sizes in all domains (Hedges g 1.15 to 2.20). Conclusion: HFS performed better than CBD in developing clinical reasoning, communication, attitude, and leadership in undergraduate medical students in pediatric emergency care, but no significant difference was observed in self-confidence and theoretical knowledge.

High-fidelity simulation versus case-based discussion for training undergraduate medical students in pediatric emergencies: a quasi-experimental study.

OBJECTIVE: To evaluate the effect of high-fidelity simulation of pediatric emergencies compared to case-based discussion on the development of self-confidence, theoretical knowledge, clinical reasoning, communication, attitude, and leadership in undergraduate medical students. METHODS: 33 medical students were allocated to two teaching methods: high-fidelity simulation (HFS, n = 18) or case-based discussion (CBD, n = 15). Self-confidence and knowledge tests were applied before and after the interventions and the effect of HFS on both outcomes was estimated with mixed-effect models. An Objective Structured Clinical Examination activity was conducted after the interventions, while two independent raters used specific simulation checklists to assess clinical reasoning, communication, attitude, and leadership. The effect of HFS on these outcomes was estimated with linear and logistic regressions. The effect size was estimated with the Hedge's g. RESULTS: Both groups had an increase in self-confidence (HFS 59.1 × 93.6, p < 0.001; CDB 50.5 × 88.2, p < 0.001) and knowledge scores over time (HFS 45.1 × 63.2, p = 0.001; CDB 43.5 × 56.7, p-value < 0.01), but no difference was observed between groups (group*time effect in the mixed effect models adjusted for the student ranking) for both tests (p = 0.6565 and p = 0.3331, respectively). The simulation checklist scores of the HFS group were higher than those of the CBD group, with large effect sizes in all domains (Hedges g 1.15 to 2.20). CONCLUSION: HFS performed better than CBD in developing clinical reasoning, communication, attitude, and leadership in undergraduate medical students in pediatric emergency care, but no significant difference was observed in self-confidence and theoretical knowledge.

Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study.

Introduction: Despite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin. Methods: To further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. Results: Analyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C. Discussion: These data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics.

Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff.

OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

Clinical features, electroencephalogram, and biomarkers in pediatric sepsis-associated encephalopathy.

To date, no specific diagnostic criteria for sepsis-associated encephalopathy (SAE) have been established. We studied 33 pediatric patients with sepsis prospectively and evaluated the level of consciousness, the presence of delirium, electroencephalographic (EEG) findings, and plasma levels of neuron-specific enolase and S100-calcium-binding protein-B. A presumptive diagnosis of SAE was primarily considered in the presence of a decreased level of consciousness and/or delirium (clinical criteria), but specific EEG abnormalities were also considered (EEG criteria). The time course of the biomarkers was compared between groups with and without clinical or EEG criteria. The Functional Status Scale (FSS) was assessed at admission, discharge, and 3-6 months post-discharge. Clinical criteria were identified in 75.8% of patients, EEG criteria in 26.9%, both in 23.1%, and none in 23.1%. Biomarkers did not differ between groups. Three patients had an abnormal FSS at discharge, but no one on follow-up. A definitive diagnostic pattern for SAE remained unclear. Clinical criteria should be the basis for diagnosis, but sedation may be a significant confounder, also affecting EEG interpretation. The role of biomarkers requires a better definition. The diagnosis of SAE in pediatric patients remains a major challenge. New consensual diagnostic definitions and mainly prognostic studies are needed.

NR3C1 gene methylation and cortisol levels in preterm and healthy full-term infants in the first 3 months of life.

Aim: To describe NR3C1 exon-1F methylation and cortisol levels in newborns. Materials & methods: Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). Results: 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Conclusion: Hypermethylated sites in NR3C1 at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.

We investigated the methylation of a gene, NR3C1 exon-1F, and cortisol levels in newborns. DNA methylation is a biochemical process that can modify gene activity. In the case of this gene, higher methylation might be associated with higher cortisol levels. We studied 46 preterm infants (born weighing 1500 g or less) and 49 full-term infants. Our results revealed that the preterm infants had hypermethylation at birth and higher cortisol levels on day 5, but decreasing methylation and stable cortisol levels over time. Meanwhile, methylation remained stable and cortisol levels increased in full-term babies with time. These unexpected results suggest that prematurity can be associated with prenatal epigenetic changes in the NR3C1 gene, but postnatal factors may induce further modifications. More research is needed to understand these findings better.

Cross-cultural adaptation of the Richmond Agitation-Sedation Scale to Brazilian Portuguese for the evaluation of sedation in pediatric intensive care. / Adaptação transcultural para o Brasil da Richmond Agitation-Sedation Scale para avaliação da sedação em terapia intensiva pediátrica.

OBJECTIVE: To perform a cross-cultural adaptation of the Richmond Agitation-Sedation Scale (RASS) to Brazilian Portuguese for the evaluation of sedation in pediatric intensive care. METHODS: Cross-cultural adaptation process including the conceptual, item, semantic and operational equivalence stages according to current recommendations. RESULTS: Pretests, divided into two stages, included 30 professionals from the pediatric intensive care unit of a university hospital, who administered the translated RASS to patients aged 29 days to 18 years. The pretests showed a content validity index above 0.90 for all items: 0.97 in the first stage of pretests and 0.99 in the second. CONCLUSION: The cross-cultural adaptation of RASS to Brazilian Portuguese resulted in a version with excellent comprehensibility and acceptability in a pediatric intensive care setting. Reliability and validity studies should be performed to evaluate the psychometric properties of the Brazilian Portuguese version of the RASS.

OBJETIVO: Realizar adaptação transcultural para o Brasil da Richmond Agitation-Sedation Scale (RASS) para avaliação da sedação em terapia intensiva pediátrica. MÉTODOS: Processo de adaptação transcultural incluindo as etapas de equivalência conceitual, de itens, semântica e operacional, de acordo com recomendações atuais. RESULTADOS: Pré-testes, divididos em duas etapas, incluíram 30 profissionais da unidade de terapia intensiva pediátrica de um hospital universitário, que aplicaram a RASS traduzida em pacientes de 29 dias a 18 anos. Os pré-testes mostraram Índice de Validade de Conteúdo acima de 0,90 para todos os itens: 0,97 na primeira etapa de pré-testes e 0,99 na segunda. CONCLUSÃO: A adaptação transcultural da RASS para o português do Brasil resultou em versão com excelente compreensão e aceitabilidade em cenário de terapia intensiva pediátrica. Estudos de confiabilidade e de validade devem ser realizados para avaliar as propriedades psicométricas da versão adaptada para o português do Brasil da RASS.

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis.

The occurrence of fetal and neonatal disorders in pregnant women with Zika virus infection in the literature is not consistent. This study aims to estimate the prevalence rate of these disorders in fetuses/neonates of pregnant women with confirmed or probable infection by Zika virus. A systematic review with meta-analysis was conducted in November 2020. Cohort studies that contained primary data on the prevalence of unfavorable outcomes in fetuses or neonates of women with confirmed or probable Zika virus infection during pregnancy were included. A total of 21 cohort studies were included, with a total of 35,568 pregnant women. The meta-analysis showed that central nervous system abnormalities had the highest prevalence ratio of 0.06 (95% CI 0.03-0.09). Intracranial calcifications had a prevalence ratio of 0.01 (95% CI 0.01-0.02), and ventriculomegaly 0.01 (95% CI 0.01-0.02). The prevalence ratio of microcephaly was 0.03 (95% CI 0.02-0.05), fetal loss (miscarriage and stillbirth) was 0.04 (95% CI 0.02-0.06), Small for Gestational Age was 0.04 (95% CI 0.00-0,09), Low Birth Weight was 0.05 (95% CI 0.03-0.08) and Prematurity was 0.07 (95% CI 0.04-0.10). The positivity in RT-PCR for ZIKV performed in neonates born to infected mothers during pregnancy was 0.25 (95% CI 0.06-0.44). We also performed the meta-analysis of meta-analysis for microcephaly with the prevalence ratios from other two previously systematic reviews: 0.03 (95% CI 0.00-0.25). Our results contribute to measuring the impact of Zika virus infection during pregnancy on children's health. The continuous knowledge of this magnitude is essential for the implementation development of health initiatives and programs, in addition to promoting disease prevention, especially in the development of a vaccine for Zika virus. PROSPERO protocol registration: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019125543.

Adaptação transcultural para o Brasil da Richmond Agitation-Sedation Scale para avaliação da sedação em terapia intensiva pediátrica / Cross-cultural adaptation of the Richmond Agitation-Sedation Scale to Brazilian Portuguese for the evaluation of sedation in pediatric intensive care

RESUMO Objetivo: Realizar adaptação transcultural para o Brasil da Richmond Agitation-Sedation Scale (RASS) para avaliação da sedação em terapia intensiva pediátrica Métodos: Processo de adaptação transcultural incluindo as etapas de equivalência conceitual, de itens, semântica e operacional, de acordo com recomendações atuais. Resultados: Pré-testes, divididos em duas etapas, incluíram 30 profissionais da unidade de terapia intensiva pediátrica de um hospital universitário, que aplicaram a RASS traduzida em pacientes de 29 dias a 18 anos. Os pré-testes mostraram Índice de Validade de Conteúdo acima de 0,90 para todos os itens: 0,97 na primeira etapa de pré-testes e 0,99 na segunda. Conclusão: A adaptação transcultural da RASS para o português do Brasil resultou em versão com excelente compreensão e aceitabilidade em cenário de terapia intensiva pediátrica. Estudos de confiabilidade e de validade devem ser realizados para avaliar as propriedades psicométricas da versão adaptada para o português do Brasil da RASS.

ABSTRACT Objective: To perform a cross-cultural adaptation of the Richmond Agitation-Sedation Scale (RASS) to Brazilian Portuguese for the evaluation of sedation in pediatric intensive care. Methods: Cross-cultural adaptation process including the conceptual, item, semantic and operational equivalence stages according to current recommendations. Results: Pretests, divided into two stages, included 30 professionals from the pediatric intensive care unit of a university hospital, who administered the translated RASS to patients aged 29 days to 18 years. The pretests showed a content validity index above 0.90 for all items: 0.97 in the first stage of pretests and 0.99 in the second. Conclusion: The cross-cultural adaptation of RASS to Brazilian Portuguese resulted in a version with excellent comprehensibility and acceptability in a pediatric intensive care setting. Reliability and validity studies should be performed to evaluate the psychometric properties of the Brazilian Portuguese version of the RASS.

Normal Hearing Function in Children Prenatally Exposed to Zika Virus

Abstract Introduction The association between prenatal Zika virus infection and hearing alterations in offspring has been the object of some studies, although few have assessed children without microcephaly. However, a current trend to include prenatal Zika virus exposure in the group of risk indicators for hearing loss is noted. Objective To present a series of 27 children prenatally exposed to the Zika virus submitted to multiple hearing assessments over time. Methods A cohort of children born to symptomatic mothers with laboratorial Zika virus infection confirmation during pregnancy was submitted to an otoacoustic emission test, auditory brainstem response test (automated, neurodiagnostic and frequency-specific), audiometry, and imitanciometry over a period of 36 months since birth. The hearing assessment was performed independently of the presence of microcephaly or other apparent signs of congenital Zika syndrome. Results The hearing tests presented predominantly normal results. Some children had signs of middle ear pathology. The only microcephalic child had normal electrophysiological tests, as well as preserved audiometric thresholds, but presented altered motor responses to sound. Conclusion Prenatal exposure to Zika virus does not always determine hearing impairment. This risk seems to be more associated to the severity of the central nervous system damage. Hearing screening and follow-ups of the affected children are important, as well as further research in this area.

Normal Hearing Function in Children Prenatally Exposed to Zika Virus.

Introduction The association between prenatal Zika virus infection and hearing alterations in offspring has been the object of some studies, although few have assessed children without microcephaly. However, a current trend to include prenatal Zika virus exposure in the group of risk indicators for hearing loss is noted. Objective To present a series of 27 children prenatally exposed to the Zika virus submitted to multiple hearing assessments over time. Methods A cohort of children born to symptomatic mothers with laboratorial Zika virus infection confirmation during pregnancy was submitted to an otoacoustic emission test, auditory brainstem response test (automated, neurodiagnostic and frequency-specific), audiometry, and imitanciometry over a period of 36 months since birth. The hearing assessment was performed independently of the presence of microcephaly or other apparent signs of congenital Zika syndrome. Results The hearing tests presented predominantly normal results. Some children had signs of middle ear pathology. The only microcephalic child had normal electrophysiological tests, as well as preserved audiometric thresholds, but presented altered motor responses to sound. Conclusion Prenatal exposure to Zika virus does not always determine hearing impairment. This risk seems to be more associated to the severity of the central nervous system damage. Hearing screening and follow-ups of the affected children are important, as well as further research in this area.

Auditory findings associated with Zika virus infection: an integrative review / Achados auditivos associados à infecção pelo Zika vírus: uma revisão integrativa

Abstract Introduction: Possible associations between Zika virus infection and hearing loss were observed during the epidemic in the Americas. Objective: To describe the auditory alterations, pathogenesis and recommendations for follow-up in individuals with prenatal or acquired Zika virus infection. Methods: Bibliographic research conducted in March/2018-April/2019 at the main available databases. Article selection, data extraction and quality evaluation were carried out by two independent reviewers. Studies containing auditory evaluation of patients with congenital or acquired Zika virus infection; and/or hypotheses or evidences on the pathophysiology of auditory impairment associated with Zika virus; and/or recommendations on screening and follow-up of patients with auditory impairment by Zika virus were included. Results: A total of 27 articles were selected. Sensorineural and transient hearing loss were reported in six adults with acquired Zika virus infection. Of the 962 studied children, 482 had microcephaly and 145 had diagnostic confirmation of Zika virus; 515 of the 624 children with auditory evaluation performed only screening tests with otoacoustic emissions testing and/or automated click-stimuli auditory brainstem response testing. Studies in prenatally exposed children were very heterogeneous and great variations in the frequency of altered otoacoustic emissions and automated click-stimuli auditory brainstem response occurred across the studies. Altered otoacoustic emissions varied from 0% to 75%, while altered automated click-stimuli auditory brainstem response varied from 0% to 29.2%. Sensorineural, retrocochlear or central origin impairment could not be ruled out. One study with infected mice found no microscopic damage to cochlear hair cells. Studies on the pathogenesis of auditory changes in humans are limited to hypotheses and recommendations still include points of controversy. Conclusion: The available data are still insufficient to understand the full spectrum of the involvement of the auditory organs by Zika virus, the pathogenesis of this involvement or even to confirm the causal association between auditory involvement and virus infection. The screening and follow-up recommendations still present points of controversy.

Resumo Introdução: Possíveis associações entre a infecção pelo Zika vírus e perda auditiva foram observadas durante a epidemia nas Américas. Objetivo: Descrever as alterações auditivas, a patogênese e as recomendações de seguimento em indivíduos com infecção por Zika vírus pré-natal ou adquirida. Método: Uma pesquisa bibliográfica foi realizada em março/2018 a abril/2019 nas principais bases de dados disponíveis. A seleção dos artigos, extração de dados e avaliação de qualidade foram realizadas por dois revisores independentes. Estudos com avaliação auditiva de pacientes com infecção por Zika vírus congênita ou adquirida; e/ou hipóteses ou evidências sobre a fisiopatologia do comprometimento auditivo associado ao Zika vírus; e/ou recomendações sobre triagem e seguimento de pacientes com comprometimento auditivo pelo Zika vírus foram incluídos na pesquisa. Resultados: Um total de 27 artigos foram selecionados. Perdas auditivas neurossensorial e transitória foram relatadas em seis adultos com infecção pelo Zika vírus adquirida. Das 962 crianças estudadas, 482 apresentavam microcefalia e 145 tinham confirmação diagnóstica do Zika vírus; 515 das 624 crianças com avaliação auditiva haviam realizado apenas testes de triagem com teste de emissões otoacústicas e/ou teste de potencial evocado auditivo de tronco encefálico automático com estímulo clique. Estudos em crianças expostas no período pré-natal foram muito heterogêneos e grandes variações na frequência de emissões otoacústicas e potencial evocado auditivo de tronco encefálico automático alterados ocorreram ao longo dos estudos; alterações nas emissões otoacústicas variaram de 0% a 75%, enquanto as alterações no potencial evocado auditivo de tronco encefálico automático variaram de 0% a 29,2%. Não foi possível descartar comprometimento neurossensorial, retrococlear ou de origem central. Um estudo com camundongos infectados não encontrou dano microscópico nas células ciliadas da cóclea. Estudos sobre a patogênese das alterações auditivas em humanos estão limitados a hipóteses e recomendações ainda apresentam pontos de controvérsia. Conclusão: Os dados disponíveis ainda são insuficientes para compreender todo o espectro do envolvimento dos órgãos auditivos pelo Zika vírus, a patogênese desse envolvimento ou até mesmo para confirmar a associação causal entre o envolvimento auditivo e a infecção pelo vírus. As recomendações de triagem e seguimento ainda apresentam pontos de controvérsia.

Auditory findings associated with Zika virus infection: an integrative review.

INTRODUCTION: Possible associations between Zika virus infection and hearing loss were observed during the epidemic in the Americas. OBJECTIVE: To describe the auditory alterations, pathogenesis and recommendations for follow-up in individuals with prenatal or acquired Zika virus infection. METHODS: Bibliographic research conducted in March/2018-April/2019 at the main available databases. Article selection, data extraction and quality evaluation were carried out by two independent reviewers. Studies containing auditory evaluation of patients with congenital or acquired Zika virus infection; and/or hypotheses or evidences on the pathophysiology of auditory impairment associated with Zika virus; and/or recommendations on screening and follow-up of patients with auditory impairment by Zika virus were included. RESULTS: A total of 27 articles were selected. Sensorineural and transient hearing loss were reported in six adults with acquired Zika virus infection. Of the 962 studied children, 482 had microcephaly and 145 had diagnostic confirmation of Zika virus; 515 of the 624 children with auditory evaluation performed only screening tests with otoacoustic emissions testing and/or automated click-stimuli auditory brainstem response testing. Studies in prenatally exposed children were very heterogeneous and great variations in the frequency of altered otoacoustic emissions and automated click-stimuli auditory brainstem response occurred across the studies. Altered otoacoustic emissions varied from 0% to 75%, while altered automated click-stimuli auditory brainstem response varied from 0% to 29.2%. Sensorineural, retrocochlear or central origin impairment could not be ruled out. One study with infected mice found no microscopic damage to cochlear hair cells. Studies on the pathogenesis of auditory changes in humans are limited to hypotheses and recommendations still include points of controversy. CONCLUSION: The available data are still insufficient to understand the full spectrum of the involvement of the auditory organs by Zika virus, the pathogenesis of this involvement or even to confirm the causal association between auditory involvement and virus infection. The screening and follow-up recommendations still present points of controversy.

Reliability of triage systems for paediatric emergency care: a systematic review.

OBJECTIVE: To present a systematic review on the reliability of triage systems for paediatric emergency care. METHODS: A search of MEDLINE, Cochrane Library, Latin American and Caribbean Health Sciences Literature, Scientific Electronic Library Online, Nursing Database Index and Spanish Health Sciences Bibliographic Index for articles in English, French, Portuguese or Spanish was conducted to identify reliability studies of five-level triage systems for patients aged 0-18 years published up to April 2018. Two reviewers performed study selection, data extraction and quality assessment as recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Twenty studies on nine triage systems were selected: the National Triage System (n=1); the Australasian Triage Scale (n=3); the paediatric Canadian Triage and Acuity Scale (PedCTAS) (n=5); the Manchester Triage System (MTS) (n=1); the Emergency Severity Index (ESI) (n=5); an adaptation of the South African Triage Scale for the Princess Marina Hospital in Botswana (n=1); the Soterion Rapid Triage System (n=1); the Rapid Emergency Triage and Treatment System-paediatric version (n=2); the Paediatric Risk Classification Protocol (n=1). Ten studies were performed with actual patients, while the others used hypothetical scenarios. The studies were rated low (n=14) or moderate (n=6) quality. Kappa was the most used statistic, although many studies did not specify the weighting. PedCTAS, MTS and ESI V.4 exhibited substantial to almost perfect agreement in moderate quality studies. CONCLUSIONS: There is some evidence on the reliability of the PedCTAS, MTS and ESI V.4, but most studies are limited to the countries where they were developed. Efforts are needed to improve the quality of the studies, and cross-cultural adaptation of those tools is recommended in countries with different professional qualification and sociocultural contexts.

Translation and cross-cultural adaptation of the Pediatric Confusion Assessment Method for the Intensive Care Unit into Brazilian Portuguese for the detection of delirium in pediatric intensive care units. / Tradução e adaptação transcultural para o Brasil do Pediatric Confusion Assessment Method for the Intensive Care Unit para detecção de delirium em unidades de terapia intensiva pediátrica.

OBJECTIVE: To undertake the translation and cross-cultural adaption into Brazilian Portuguese of the Pediatric Confusion Assessment Method for the Intensive Care Unit for the detection of delirium in pediatric intensive care units, including the algorithm and instructions. METHODS: A universalist approach for the translation and cross-cultural adaptation of health measurement instruments was used. A group of pediatric critical care specialists assessed conceptual and item equivalences. Semantic equivalence was evaluated by means of a translation from English to Portuguese by two independent translators; reconciliation into a single version; back-translation by a native English speaker; and consensus among six experts with respect to language and content understanding by means of Likert scale responses and the Content Validity Index. Finally, operational equivalence was assessed by applying a pre-test to 30 patients. RESULTS: The back-translation was approved by the original authors. The medians of the expert consensus responses varied between good and excellent, except for the feature "acute onset" of the instructions. Items with a low Content Validity Index for the features "acute onset" and "disorganized thinking" were adapted. In the pre-test, the expression "signal with your head" was modified into "nod your head" for better understanding. No further adjustments were necessary, resulting in the final version for Brazilian Portuguese. CONCLUSION: The Brazilian version of the Pediatric Confusion Assessment Method for the Intensive Care Unit was generated in agreement with the international recommendations and can be used in Brazil for the diagnosis of delirium in critically ill children 5 years of age or above and with no developmental cognitive disabilities.

Co-infection with Zika and Chikungunya viruses associated with fetal death-A case report.

We describe a case of fetal death associated with a recent infection by Chikungunya virus (CHIKV) in a Brazilian pregnant woman (positive RT-PCR in blood and placenta). Zika virus (ZIKV) infection during pregnancy was also identified, based on a positive RT-PCR in a fetal kidney specimen. The maternal infection caused by the ZIKV was asymptomatic and the CHIKV infection had a classical clinical presentation. The fetus had no apparent anomalies, but her weight was between the 3rd and 10th percentile for the gestational age. This is the second case report of congenital arboviral co-infection and the first followed by antepartum fetal death.

Tradução e adaptação transcultural para o Brasil do Pediatric Confusion Assessment Method for the Intensive Care Unit para detecção de delirium em unidades de terapia intensiva pediátrica / Translation and cross-cultural adaptation of the Pediatric Confusion Assessment Method for the Intensive Care Unit into Brazilian Portuguese for the detection of delirium in pediatric intensive care units

RESUMO Objetivo: Traduzir e adaptar transculturalmente para o português do Brasil o instrumento Pediatric Confusion Assessment Method for the Intensive Care Unit para detecção de delirium em unidades de terapia intensiva pediátrica, incluindo algoritmo e instruções. Métodos: Utilizou-se a abordagem universalista para tradução e adaptação transcultural de instrumentos de aferição em saúde. Um grupo de especialistas em terapia intensiva pediátrica avaliou as equivalências conceitual e de itens. Em seguida, a avaliação da equivalência semântica consistiu de tradução do inglês para o português por dois tradutores independentes; conciliação em uma única versão; retradução por um nativo de língua inglesa; e consenso de seis especialistas quanto à compreensão de linguagem e de conteúdo, por meio de respostas do tipo Likert e Índice de Validade de Conteúdo. Finalmente, avaliou-se a equivalência operacional, aplicando-se um pré-teste em 30 pacientes. Resultados: A retradução foi aprovada pelos autores originais. As medianas das respostas do consenso variaram de boa a excelente, exceto na característica "início agudo" das instruções. Itens com Índice de Validade de Conteúdo baixo, relativos às características "início agudo" e "pensamento desorganizado", foram adaptados. No pré-teste, a expressão "acene com a cabeça" foi modificada para "balance a cabeça", para melhor compreensão. Não houve necessidade de outros ajustes, resultando na versão final para o português do Brasil. Conclusão: A versão brasileira do Pediatric Confusion Assessment Method for the Intensive Care Unit foi obtida segundo as recomendações internacionais, podendo ser utilizada no Brasil para o diagnóstico de delirium em crianças graves com 5 anos de idade ou mais, sem atraso de desenvolvimento cognitivo.

ABSTRACT Objective: To undertake the translation and cross-cultural adaption into Brazilian Portuguese of the Pediatric Confusion Assessment Method for the Intensive Care Unit for the detection of delirium in pediatric intensive care units, including the algorithm and instructions. Methods: A universalist approach for the translation and cross-cultural adaptation of health measurement instruments was used. A group of pediatric critical care specialists assessed conceptual and item equivalences. Semantic equivalence was evaluated by means of a translation from English to Portuguese by two independent translators; reconciliation into a single version; back-translation by a native English speaker; and consensus among six experts with respect to language and content understanding by means of Likert scale responses and the Content Validity Index. Finally, operational equivalence was assessed by applying a pre-test to 30 patients. Results: The back-translation was approved by the original authors. The medians of the expert consensus responses varied between good and excellent, except for the feature "acute onset" of the instructions. Items with a low Content Validity Index for the features "acute onset" and "disorganized thinking" were adapted. In the pre-test, the expression "signal with your head" was modified into "nod your head" for better understanding. No further adjustments were necessary, resulting in the final version for Brazilian Portuguese. Conclusion: The Brazilian version of the Pediatric Confusion Assessment Method for the Intensive Care Unit was generated in agreement with the international recommendations and can be used in Brazil for the diagnosis of delirium in critically ill children 5 years of age or above and with no developmental cognitive disabilities.

Validity of triage systems for paediatric emergency care: a systematic review.

AIM: To present a systematic review on the validity of triage systems for paediatric emergency care. METHODS: Search in MEDLINE, Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), Scientific Electronic Library Online (SciELO), Nursing Database Index (BDENF) and Spanish Health Sciences Bibliographic Index (IBECS) for articles in English, French, Portuguese or Spanish with no time limit. Validity studies of five-level triage systems for patients 0-18 years old were included. Two reviewers performed data extraction and quality assessment as recommended by PRISMA statement. RESULTS: We found 25 studies on seven triage systems: Manchester Triage System (MTS); paediatric version of Canadian Triage and Acuity Scale (PedCTAS) and its adaptation for Taiwan (paediatric version of the Taiwan Triage and Acuity System); Emergency Severity Index version 4 (ESI v.4); Soterion Rapid Triage System and South African Triage Scale and its adaptation for Bostwana (Princess Marina Triage Scale). Only studies on the MTS used a reference standard for urgency, while all systems were evaluated using a proxy outcome for urgency such as admission. Over half of all studies were low quality. The MTS, PedCTAS and ESI v.4 presented the largest number of moderate and high quality studies. The three tools performed better in their countries or near them, showing a consistent association with hospitalisation and resource utilisation. Studies of all three tools found that patients at the lowest urgency levels were hospitalised, reflecting undertriage. CONCLUSIONS: There is some evidence to corroborate the validity of the MTS, PedCTAS and ESI v.4 for paediatric emergency care in their own countries or near them. Efforts to improve the sensitivity and to minimise the undertriage rates should continue. Cross-cultural adaptation is necessary when adopting these triage systems in other countries.

Prevalence of microcephaly in eight south-eastern and midwestern Brazilian neonatal intensive care units: 2011-2015.

OBJECTIVE: To describe the prevalence of microcephaly in infants admitted to the neonatal intensive care units (NICUs) in eight private hospitals in south-eastern and midwestern Brazil, from 2011 to 2015. DESIGN: Observational, cross-sectional study in a cohort of neonates. SETTING: Eight private NICUs situated in the cities of Rio de Janeiro (RJ), São Paulo (SP) and Federal District of Brasilia (FDB). PATIENTS: Neonates up to 7 days of age and >23 weeks of gestational age. MAIN OUTCOME MEASURES: Primary outcomes were the annual prevalence of microcephaly and severe microcephaly, both overall and in subgroups according to gestational age, type of microcephaly (proportional or disproportional) and the NICU's location in RJ, SP or FDB. RESULTS: In this cohort of 8275 neonates admitted to eight private NICUs, the overall prevalence of microcephaly was 5.6% (95% CI 5.1% to 6.1%) and severe microcephaly, 1.5% (95% CI 1.2% to 1.7%). There was no annual variation in these overall estimates (p=0.48 and p=0.99, respectively), nor in the studied subgroups. Microcephaly prevalence was higher in extremely premature and term newborns (7.7% and 7.2%; p<0.001, respectively). Disproportional microcephaly was much more common than proportional microcephaly (prevalence 5.0% vs 0.6%; p<0.001). CONCLUSIONS: The prevalence of microcephaly showed little variation from 2011 to 2015 in these south-eastern and midwestern Brazilian NICUs, suggesting that the impact of the Zika epidemic in neonates that occurred mainly in the north-eastern region in 2015 did not yet affect the infants of those regions during the studied period. These prevalence results can serve as a reference for comparisons with any future Zika outbreaks in the same or similar populations from these regions.