CLARIPED: a new tool for risk classification in pediatric emergencies

AbstractObjectiveTo present a new pediatric risk classification tool, CLARIPED, and describe its development steps.MethodsDevelopment steps: (i) first round of discussion among experts, first prototype; (ii) pre-test of reliability, 36 hypothetical cases; (iii) second round of discussion to perform adjustments; (iv) team training; (v) pre-test with patients in real time; (vi) third round of discussion to perform new adjustments; (vii) final pre-test of validity (20% of medical treatments in five days).ResultsCLARIPED features five urgency categories: Red (Emergency), Orange (very urgent), Yellow (urgent), Green (little urgent) and Blue (not urgent). The first classification step includes the measurement of four vital signs (VIPE score); the second step consists in the urgency discrimination assessment. Each step results in assigning a color, selecting the most urgent one for the final classification. Each color corresponds to a maximum waiting time for medical care and referral to the most appropriate physical area for the patient's clinical condition. The interobserver agreement was substantial (kappa=0.79) and the final pre-test, with 82 medical treatments, showed good correlation between the proportion of patients in each urgency category and the number of used resources (p<0.001).ConclusionsCLARIPED is an objective and easy-to-use tool for simple risk classification, of which pre-tests suggest good reliability and validity. Larger-scale studies on its validity and reliability in different health contexts are ongoing and can contribute to the implementation of a nationwide pediatric risk classification system

CLARIPED: um novo instrumento para classificação de risco em emergências pediátricas

ResumoObjetivoApresentar um novo instrumento de classificação de risco pediátrico, o CLARIPED, e descrever as etapas de seu desenvolvimento.MétodosEtapas do desenvolvimento: (i) primeira rodada de discussão entre especialistas, primeiro protótipo; (ii) pré‐teste de confiabilidade, 36 casos hipotéticos; (iii) segunda rodada de discussão para ajustes; (iv) treinamento da equipe; (v) pré‐teste com pacientes em tempo real; (vi) terceira rodada de discussão para novos ajustes; (vii) pré‐teste final de validade (20% dos atendimentos de cinco dias).ResultadosO CLARIPED apresenta cinco categorias de urgência: Vermelha (emergência), Laranja (muito urgente), Amarela (urgente), Verde (pouco urgente) e Azul (sem urgência). A primeira etapa da classificação inclui a aferição de quatro sinais vitais (escore Vipe); a segunda etapa consiste na avaliação de discriminadores de urgência. Cada etapa resulta na atribuição de uma cor, seleciona‐se a de maior urgência para a classificação final. Cada cor corresponde a um tempo máximo de espera pelo atendimento médico e ao encaminhamento à área física mais adequada à condição clínica do paciente. A concordância interobservador foi substancial (kappa=0,79) e o pré‐teste final, com 82 atendimentos, evidenciou boa correlação entre a proporção de pacientes em cada categoria de urgência e o número de recursos usados (p<0,001).ConclusõesO CLARIPED é um instrumento para classificação de risco simples, objetivo e de fácil uso, cujos pré‐testes sugerem boa confiabilidade e validade. Estudos em maior escala sobre sua validade e confiabilidade em diferentes contextos de saúde estão em curso e podem contribuir para a adoção de um sistema de classificação de risco pediátrico em âmbito nacional.AbstractObjectiveTo present a new pediatric risk classification tool, CLARIPED, and describe its development steps.MethodsDevelopment steps: (i) first round of discussion among experts, first prototype; (ii) pre‐test of reliability, 36 hypothetical cases; (iii) second round of discussion to perform adjustments; (iv) team training; (v) pre‐test with patients in real time; (vi) third round of discussion to perform new adjustments; (vii) final pre‐test of validity (20% of medical treatments in five days).ResultsCLARIPED features five urgency categories: Red (Emergency), Orange (very urgent), Yellow (urgent), Green (little urgent) and Blue (not urgent). The first classification step includes the measurement of four vital signs (Vipe score); the second step consists in the urgency discrimination assessment. Each step results in assigning a color, selecting the most urgent one for the final classification. Each color corresponds to a maximum waiting time for medical care and referral to the most appropriate physical area for the patient's clinical condition. The interobserver agreement was substantial (kappa=0.79) and the final pre‐test, with 82 medical treatments, showed good correlation between the proportion of patients in each urgency category and the number of used resources (p<0.001).ConclusionsCLARIPED is an objective and easy‐to‐use tool for simple risk classification, of which pre‐tests suggest good reliability and validity. Larger‐scale studies on its validity and reliability in different health contexts are ongoing and can contribute to the implementation of a nationwide pediatric risk classification system

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

Mortalidade hospitalar por covid-19 em crianças e adolescentes no Brasil em 2020–2021

OBJECTIVE: To describe cases, deaths, and hospital mortality from covid-19 in children andadolescents in Brazil, according to age group, during the evolving phases of the pandemic in2020 and 2021.METHODS: Census of patients aged up to 19 committed with severe acute respiratory syndrome, due to covid-19 or unspecified, notified to the Brazilian Influenza Epidemiological Surveillance Information System, from January 1, 2020, to December 31, 2021. The two years were divided into six phases, covering the spread of the disease—first, second and third wave—as well as the impact of vaccination. The pediatric population was categorized into infants, preschoolers, schoolchildren, and adolescents. Hospital mortality was assessed by pandemic phase and age group.RESULTS: A total of 144,041 patients were recorded in the two years, 18.2% of whom had confirmed cases of covid-19. Children under 5 years old (infants and preschoolers) accounted for 62.8% of those hospitalized. A total of 4,471 patients died, representing about 6.1 deaths per day. Infants were the ones who most progressed to the intensive care unit (24.7%) and had the highest gross number of deaths (n = 2,012), but mortality was higher among adolescents (5.7%), reaching 9.8% in phase 1. The first peak of deaths occurred in phase 1 (May/2020), and two other peaks occurred in phase 4 (March/2021 and May/2021). There was an increase in cases and deaths for younger ages since phase 4. Hospital mortality in the pediatric population washigher in phases 1, 4, and 6, following the phenomena of dissemination/interiorization of thevirus in the country, beginning of the second wave and beginning of the third wave, respectively.CONCLUSION: The absolute number of cases o f covid-19 in children and adolescents is significant. Although complete vaccination in descending order of age provided a natural deviation in age range, there was a greater gap between the curve of new hospitalized cases and the curve of deaths, indicating the positive impact of immunization.OBJETIVO: Descrever casos, óbitos e mortalidade hospitalar por covid-19 em crianças e adolescentes no Brasil, conforme faixa etária, durante as fases de evolução da pandemia em 2020 e 2021. MÉTODOS: Censo de pacientes de até 19 anos internados com síndrome respiratória aguda grave, por covid-19 ou não especificada, notificados ao Sistema de Informação de Vigilância Epidemiológica da Gripe do Brasil, entre 1 de janeiro de 2020 e 31 de dezembro de 2021. Os dois anos foram divididos em seis fases, abrangendo a disseminação da doença − primeira, segunda e terceira onda −, bem como o impacto da vacinação. A população pediátrica foi categorizada em lactentes, pré-escolares, escolares e adolescentes. A mortalidade hospitalar foi avaliada por fase da pandemia e faixa etária. RESULTADOS: Foram contabilizados 144.041 pacientes nos dois anos, sendo 18,2% casos de covid-19 confirmados. Menores de 5 anos (lactentes e pré-escolares) corresponderam a 62,8% dos hospitalizados. Evoluíram a óbito 4.471, representando cerca 6,1 óbitos por dia. Os lactentes foram os que mais evoluíram para unidade de terapia intensiva (24,7%) e apresentaram o maior número bruto de óbito (n = 2.012), porém a mortalidade foi maior entre os adolescentes (5,7%), chegando a 9,8% na fase 1. O primeiro pico de óbitos ocorreu na fase 1 (maio/2020), e outros dois picos ocorreram na fase 4 (março/2021 e maio/2021). Verificou-se avanço de casos e óbitos para as idades inferiores desde a fase 4. A mortalidade hospitalar na população pediátrica foi maior nas fases 1, 4 e 6, acompanhando os fenômenos de disseminação/interiorização do vírus no país, início da segunda onda e início da terceira onda, respectivamente. CONCLUSÃO: O número absoluto de casos de covid-19 em crianças e adolescentes é expressivo. Embora a vacinação completa em ordem decrescente de idade tenha proporcionado um desvio natural de faixa etária, ocorreu um distanciamento maior entre a curva de novos casos hospitalizados e a curva de óbitos, indicando o impacto positivo da imunização

The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by zika virus

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water sup-plies of NE compared to other regions of Brazil. Experimentally, we described that STX dou-bled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.Fil: Pedrosa, Carolina da S. G.. D’Or Institute for Research and Education; BrasilFil: Souza, Leticia R. Q.. D’Or Institute for Research and Education; BrasilFil: Gomes, Tiago A.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Oswaldo Cruz; BrasilFil: de Lima, Caroline V. F.. D’Or Institute for Research and Education; BrasilFil: Ledur, Pitia F.. D’Or Institute for Research and Education; BrasilFil: Karmirian, Karina. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Barbeito Andrés, Jimena. Universidade Federal do Rio de Janeiro; Brasil. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Costa, Marcelo do N.. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, Luiza M.. Universidade Federal do Rio de Janeiro; BrasilFil: Rossi, Átila D.. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, Amilcar. Universidade Federal do Rio de Janeiro; BrasilFil: Prata Barbosa, Arnaldo. D’Or Institute for Research and Education; BrasilFil: Tovar Moll, Fernanda. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Garcez, Patricia P.. Universidade Federal do Rio de Janeiro; BrasilFil: Lara, Flavio A.. Instituto Oswaldo Cruz; BrasilFil: Molica, Renato J. R.. Universidad Federal Rural Pernambuco; BrasilFil: Rehen, Stevens K.. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; Brasi

Multicenter validation of PIM3 and PIM2 in Brazilian pediatric intensive care units

ObjectiveTo validate the PIM3 score in Brazilian PICUs and compare its performance with the PIM2.MethodsObservational, retrospective, multicenter study, including patients younger than 16 years old admitted consecutively from October 2013 to September 2019. We assessed the Standardized Mortality Ratio (SMR), the discrimination capability (using the area under the receiver operating characteristic curve – AUROC), and the calibration. To assess the calibration, we used the calibration belt, which is a curve that represents the correlation of predicted and observed values and their 95% Confidence Interval (CI) through all the risk ranges. We also analyzed the performance of both scores in three periods: 2013–2015, 2015–2017, and 2017–2019.Results41,541 patients from 22 PICUs were included. Most patients aged less than 24 months (58.4%) and were admitted for medical conditions (88.6%) (respiratory conditions = 53.8%). Invasive mechanical ventilation was used in 5.8%. The median PICU length of stay was three days (IQR, 2–5), and the observed mortality was 1.8% (763 deaths). The predicted mortality by PIM3 was 1.8% (SMR 1.00; 95% CI 0.94–1.08) and by PIM2 was 2.1% (SMR 0.90; 95% CI 0.83–0.96). Both scores had good discrimination (PIM3 AUROC = 0.88 and PIM2 AUROC = 0.89). In calibration analysis, both scores overestimated mortality in the 0%–3% risk range, PIM3 tended to underestimate mortality in medium-risk patients (9%–46% risk range), and PIM2 also overestimated mortality in high-risk patients (70%–100% mortality risk).ConclusionsBoth scores had a good discrimination ability but poor calibration in different ranges, which deteriorated over time in the population studied

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

IntroductionDespite 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.MethodsTo further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. ResultsAnalyses 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.DiscussionThese 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

Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec