How to incorporate telemedicine in medical residency: A Brazilian experience in pediatric emergency

ABSTRACT Introduction: The exponential growth of telehealth services during the COVID-19 pandemic led to the implementation of a telemedicine care service in a tertiary university pediatric hospital. It brought the need to develop a training aimed at remote care within the pediatric emergency rotation program. Objective: To describe the implementation of a telemedicine training for pediatric residents and present the preliminary results. Methods: Descriptive prospective study (pre and post), with 40 resident physicians of the first year of pediatrics. Reaction Assessments were applied before and after training, in addition to a resident physician perception questionnaire at the end of the training. Results: There was a significant difference in the resident's perception of experience and safety after initial training. Most rated the proposal as good or excellent, considered teaching telemedicine relevant and that this experience contributed to their learning on the subject. Conclusion: This study describes an innovative proposal for training in telemedicine. The preliminary results were encouraging, demonstrating the program's potential in training future pediatricians.

Pediatric emergency triage systems / Sistemas de triagem em emergência pediátrica

ABSTRACT Objective: The aim of this study was to perform a narrative review of the leading pediatric triage systems in emergency departments (EDs). Data source: Articles published between 1999 and 2019 were identified by searching the MEDLINE, EMBASE, and PubMed databases using the keywords "pediatric triage", "pediatric assessment tools", and "emergency department triage" with an emphasis on studies that evaluated the validation and reliability of triage systems. Data synthesis: A total of 105 articles on pediatric emergency triage systems in 12 countries were evaluated. Triage systems were divided into two groups: color-stratified triage systems and alert systems. The color-stratified triage systems included in this review were the Canadian Triage and Acuity Scale (CTAS), Manchester Triage System (MTS), Emergency Severity Index (ESI), and Australasian Triage Scale (ATS), and the alert systems included were the Paediatric Observation Priority Score (POPS), Pediatric Early Warning Score (PEWS), and Pediatric Approach Triangle (PAT). Evidence corroborates the validity and reliability of MTS, PaedCTAS, ESI version 4, PEWS, POPS, and PAT in pediatric emergency services. Conclusions: These are fundamental tools for risk classification of patients seeking treatment in EDs. Not all triage systems have been assessed for validity and reliability; nor are they well suited for all regions of the world. Employing triage systems in Brazil requires cultural adaptation and rigorous training of the local health staff, in addition to validation and reliability studies in our country, since the social and cultural context of this country differs from those where these tools were developed.

RESUMO Objetivo: Realizar uma revisão narrativa dos principais sistemas de triagem pediátrica nos serviços de emergência. Fontes de dados: Artigos publicados entre 1999 e 2019, obtidos por meio de busca nos bancos de dados Medical Literature Analysis and Retrieval System Online (Medline), Embase e PubMed usando as palavras-chave "pediatric triage", "pediatric assessment tools" e "emergency department triage", com ênfase em estudos que avaliaram a validação e a confiabilidade desses sistemas. Síntese dos dados: Foram avaliados 105 artigos sobre sistemas de triagem na emergência pediátrica de 12 países. Os sistemas de triagem foram divididos em dois grupos: estratificados por cores e de alerta. Os sistemas de triagem com estratificação por cores incluídos nesta revisão foram: Canadian Triage and Acuity Scale (CTAS), Manchester Triage System (MTS), Emergency Severity Index (ESI) e Australian Triage Scale (ATS). Os sistemas de alerta incluídos foram: Paediatric Observation Priority Score (POPS), Pediatric Early Warning Score (PEWS) e Pediatric Approach Triangle (PAT). Há evidências que corroboram a validade e a confiabilidade do MTS, PedCTAS, ESI v.4, PEWS, POPS e PAT em serviços de emergência de pediátricos. Conclusões: Os sistemas de triagem são ferramentas fundamentais para o atendimento de pacientes que procuram serviços de emergência. Nem todos os sistemas de triagem foram avaliados para validação e confiabilidade nem se aplicam a todas as regiões do mundo. Para a aplicação de sistemas de triagem no Brasil, devem ser feitos adaptação cultural e treinamento do estafe de saúde local, bem como estudos de validação e confiabilidade em nosso país, dado o seu contexto social e cultural diferente daquele dos países onde essas ferramentas foram desenvolvidas.

Acute upper gastrointestinal bleeding due to portal hypertension in children: What is the best timing of endoscopy?

OBJECTIVE: To compare initial clinical/laboratory parameters and outcomes of mortality/rebleeding of endoscopy performed <12 h(early UGIE) versus endoscopy performed after 12-24h(late UGIE) of ED admission in children with acute upper gastrointestinal bleeding(AUGIB) due to portal hypertension. METHODS: This is a retrospective cohort study. From January 2010 to July 2017, medical records of all children admitted to a tertiary care hospital with AUGIB due to portal hypertension were reviewed until 60 days after ED admission. RESULTS: A total of 98 ED admissions occurred from 73 patients. Rebleeding was identified in 8/98(8%) episodes, and 9 deaths were observed. UGIE was performed in 92(94%) episodes, and 53(58%) of them occurred within 12 h of ED admission. Episodes with early UGIE and late UGIE were similar in terms of history/complaints/laboratory data at admission, chronic liver disease associated, AUGIB duration, and initial management. No statistically significant associations were found between early UGIE and the outcomes of death/rebleeding and prevalence of endoscopic hemostatic treatment (band ligation or sclerotherapy) compared to late UGIE. In the multivariable logistic regression model, the endoscopic hemostatic treatment showed a negative association with early UGIE(OR=0.33;95%CI=0.1-0.9;p = 0.04). CONCLUSIONS: This study suggests that in pediatric patients with AUGIB and portal hypertension, UGIE may be performed after 12-24 h without harm to the patient, facilitating better initial clinical stabilization/treatment and optimization of resources.

Post-varicella arterial ischemic stroke in children and neurocognitive performance: a 4-year follow-up study

ABSTRACT Objective To analyze data from children who were previously healthy and presented with post-varicella arterial ischemic stroke upon arrival when admitted to the emergency room, with focus on the clinical/laboratory aspects, and neurocognitive performance after four-year follow-up. Methods Seven children presenting with arterial ischemic stroke after varicella were evaluated at pediatric emergency services in the city of São Paulo (SP), Brazil. Ischemic stroke was determined by magnetic resonance imaging/magnetic resonance angiography in a topography compatible with the areas supplied by the middle cerebral or internal carotid arteries. IgG-class antibodies against varicella zoster virus and varicella-zoster virus DNA by polymerase chain reaction in cerebrospinal fluid were tested. Patients with prothrombotic conditions were excluded. The Pediatric Stroke Outcome Measure was applied upon admission and 4-years after the stroke. Results All patients (age range: 1.3 to 4 years) included presented chickenpox 5.1 (±3.5) months before. All patients had analysis of anti-varicella-zoster-virus-IgG in cerebrospinal fluid, but only three (43%) had a positive result. Of the patients 43% had no vascular lesions identified in magnetic resonance angiography. All patients showed improvement in their sequela scores. After 4 years, five patients displayed good evolution in the Pediatric Stroke Outcome Measure, and only one patient presented with a score of 2 in the sensorimotor and cognition areas. No recurrence of arterial ischemic stroke was observed. Conclusion We reinforced the non-progressive course of post-varicella arterial ischemic stroke after 4-year follow-up. The presence of varicella-zoster-virus-DNA detected by polymerase chain reaction, and/or intrathecal IgG antibody against varicella zoster virus, and angiopathy location in magnetic resonance angiography were not determining for the diagnosis. Invasive tests, with low sensitivity, should be well considered in the diagnosis of post-varicella arterial ischemic stroke.

SARS-CoV-2 and rhinovirus infections: are there differences in clinical presentation, laboratory abnormalities, and outcomes in the pediatric population?

ABSTRACT This study aims to assess COVID-19 and other respiratory viruses in pediatric patients. Between April 17 and September 30, 2020, we collected 1,566 respiratory samples from 1,044 symptomatic patients who were younger than 18 years old to assess SARS-CoV-2 infection. Of these, 919 were analyzed for other respiratory pathogens (ORP). Patients with laboratory-confirmed COVID-19 or ORP were included. We evaluated 76 pediatric COVID-19 infections and 157 other respiratory virus infections. Rhinovirus occurred in 132/157 (84%). COVID-19 patients who were significantly older, had more fevers, headaches and pneumonia than those with ORP. The median white blood cell count was lower in patients with SARS-CoV-2 than in those with ORP (6,470 versus 8,170; p=0.02). COVID-19 patients had significantly worse symptoms than those with ORP.

Impacto na saúde mental de enfermeiros pediátricos: um estudo transversal em hospital pediátrico terciário durante a pandemia de COVID-19 / Mental health impacts in pediatric nurses: a cross-sectional study in tertiary pediatric hospital during the COVID-19 pandemic / Impacto en la salud mental de enfermeros pediátricos: un estudio transversal en un hospital pediátrico de tercer nivel durante la pandemia de COVID-19

Resumo Objetivo: avaliar problemas de saúde mental em enfermeiros pediátricos durante a pandemia causada pelo coronavírus 2019. Método: estudo transversal realizado com enfermeiros pediátricos do Instituto da Criança e do Adolescente, por meio de uma pesquisa online de autoavaliação sobre prática clínica e impacto na saúde mental, durante a pandemia de COVID-19. Foram avaliadas escalas de autoavaliação validadas para ansiedade, depressão e burnout. Resultados: 107/298(36%) enfermeiros responderam, dos quais 90% eram do sexo feminino, a mediana de idade atual era 41(23-64) anos, 68% trabalhavam com adolescentes, 66% trabalhavam na linha de frente. Burnout, ansiedade e depressão moderada/grave ocorreram em 65%, 72% e 74% dos enfermeiros, respectivamente. Falta de protocolo de tratamento padronizado nas enfermarias (27% vs. 10%, p=0,049), depressão moderada/grave (74% vs. 16%, p=0,002) e burnout (82% vs. 58%, p=0,01) foram significativamente maiores em enfermeiros pediátricos com ansiedade, em comparação com enfermeiros sem essa condição. Os enfermeiros pediátricos que trabalhavam com adolescentes apresentaram maior frequência de burnout, quando comparados aos que não trabalhavam com esse grupo (77% vs. 32%, p=0,0001). A análise multivariada revelou que o cumprimento adequado da quarentena aumentou a presença de ansiedade em 4,6 vezes [OR 4.6(IC 1,1-20,2), p=0,04]. Conclusão: a maioria dos enfermeiros pediátricos atuava na linha de frente da COVID-19, em condições precárias, trabalhando com equipe reduzida e enfrentando perdas expressivas de renda. A ansiedade atual foi um tema relevante e o burnout também foi uma condição mental importante para esses profissionais, reforçando a cultura do bom trabalho em equipe, das práticas de colaboração e do cuidado psicológico/psiquiátrico.

Abstract Objective: to assess mental health issues in pediatric nurses during coronavirus pandemic in 2019. Method: cross-sectional study was conducted with pediatric nurses at the Instituto da Criança e do Adolescente based on online self-rated survey about clinical practice and mental health impact during COVID-19 pandemic. Validated self-reported scales for anxiety, depression and burnout were used for assessing these professionals. Results: 107/298 (36%) nurses answered, 90% were female, median age was 41(23-64) years, 68% worked with adolescents, 66% in frontline. Burnout, anxiety and moderate/severe depression occurred in 65%, 72% and 74%, respectively. Lack of standardized treatment protocol for nurses (27%vs.10%, p=0.049), moderate/severe depression (74% vs. 16%, p=0.002) and burnout (82% vs. 58%, p=0.01) were significantly higher in pediatric nurses with anxiety compared to those without. Pediatric nurses that worked with adolescents compared to those that did not showed higher frequency of burnout in the former group (77% vs. 32%, p=0.0001). Multivariable analysis revealed that adequate quarantine adherence increased the presence of anxiety in 4.6 times [OR4.6(CI 1.1-20.2), p=0.04]. Conclusion: most pediatric nurses who had worked in the frontline of COVID-19 were under precarious conditions, working with reduced team, and with an expressive changes in their monthly income. Current anxiety was a relevant issue, burnout was also an important mental condition for these professionals, reinforcing culture of good teamwork, collaboration practices and psychological/psychiatric approach.

Resumen Objetivo: evaluar los problemas de salud mental en enfermeros pediátricos durante la pandemia del coronavirus 2019. Método: estudio transversal realizado con enfermeros pediátricos del Instituto da Criança e do Adolescente mediante una encuesta de autoevaluación en línea sobre la práctica clínica y el impacto en la salud mental durante la pandemia de COVID-19. Se evaluaron escalas de autoevaluación validadas para ansiedad, depresión y burnout. Resultados: respondieron 107/298 (36%) de los enfermeros, de los cuales 90% eran del sexo femenino, la mediana de edad actual fue de 41 (23-64) años, 68% trabajaban con adolescentes, 66% trabajaban en primera línea. Burnout, ansiedad y depresión moderada/grave ocurrieron en 65%, 72% y 74% de los enfermeros, respectivamente. Falta de protocolo de tratamiento estandarizado en las enfermerías (27% vs. 10%, p=0,049), depresión moderada/grave (74% vs. 16%, p=0,002) y burnout (82% vs. 58%, p=0,01) fueron significativamente mayores en enfermeros pediátricos con ansiedad en comparación con enfermeros sin esta condición. Los enfermeros pediátricos que trabajaban con adolescentes presentaron mayor frecuencia de burnout en comparación con los que no trabajaban con adolescentes (77% vs. 32%, p=0,0001). El análisis multivariado reveló que el adecuado cumplimiento de la cuarentena aumentó 4,6 veces la presencia de ansiedad [OR 4.6(IC 1,1-20,2), p=0,04]. Conclusión: La mayoría de los enfermeros pediátricos trabajaban en la primera línea de la COVID-19, en condiciones precarias, trabajando con un equipo reducido y enfrentando importantes pérdidas de ingresos. La ansiedad actual fue un tema relevante y el burnout también fue una condición mental importante para estos profesionales, reforzando la cultura del buen trabajo en equipo, las prácticas colaborativas y la atención psicológica/psiquiátrica.

Air pollution influence on serum inflammatory interleukins: A prospective study in childhood-onset systemic lupus erythematous patients.

OBJECTIVE: To assess the effect of individual exposure, in real-time, to traffic-related pollutants on serum interleukin levels of childhood-onset lupus erythematous systemic (c-SLE) patients. METHODS: A longitudinal and observational design was conducted in 12 repeated measures of serum samples and clinical evaluations (totaling 108 measurements) of c-SLE patients over 30 consecutive months. Real-time, individual exposure to fine particles (PM2.5) and nitrogen dioxide (NO2) was measured with portable monitors. Generalized estimating equation was used to evaluate the association between exposure to PM2.5 and NO2 and the following serum cytokine levels on the 7 days preceding clinical assessment and serum collection: MCP1, IL-6, IL-8, IL-10, IL-17, IFN-alpha, and TNF-alpha. Disease activity and other risk factors were also controlled. RESULTS: An interquartile range (IQR) increase in PM2.5 daily concentration was significantly associated with increased levels of TNF-alpha on the third, fourth, and seventh day after exposure; IL-10 on the third and fourth day after exposure; IL-17 on the third and seventh day after exposure; and INF-alpha on the third day after exposure (p < 0.05). An IQR increase in 7-day moving average of PM2.5 was associated with a 6.2 pg/mL (95% CI: 0.5; 11.8; p = 0.04) increase in serum IFN-alpha level. An unexpected significant association was observed between an IQR increase in NO27-day cumulative concentration and a decrease of 1.6 pg/mL (95% CI: -2.6; -0.7; p < 0.001) in serum IL-17. CONCLUSION: Real-time exposure to PM2.5 prospectively associated with increased serum TNF-alpha, INF-alpha, IL-10, and IL-17 levels in c-SLE patients.

O coração de pacientes pediátricos com COVID-19: novos insights a partir de um estudo ecocardiográfico sistemático em um Hospital Terciário no Brasil / The heart of pediatric patients with COVID-19: new insights from a systematic chocardiographic study in a Tertiary Hospital in Brazil

Resumo Fundamento A pandemia da COVID-19 representa uma enorme carga para o sistema de saúde do mundo. Apesar de pacientes pediátricos terem sido relativamente poupados em comparação a adultos, estudos recentes mostraram um número crescente de pacientes críticos com Síndrome Inflamatória Multisistêmica Pediátrica (SIM-P) com disfunção cardiovascular importante. No entanto, pouco se conhece a respeito da relação entre anormalidades cardíacas e biomarcadores inflamatórios e de coagulação. Objetivos Investigar anormalidades ecocardiográficas em pacientes pediátricos com COVID-19 admitidos em um hospital terciário. Métodos Este foi um estudo longitudinal retrospectivo, baseado na revisão de prontuários médicos e ecocardiogramas de pacientes (0-19 anos) admitidos em um hospital terciário entre 30 de março e 30 de junho de 2020. Para a análise estatística, o nível de significância foi estabelecido em 5% (p<0,05). Resultados Foram incluídos 48 pacientes, 73% com doenças pré-existentes, 20 (41,7%) com SIM-P. A idade mediana foi 7,5 (0-18,6) anos; 27 (56,2%) eram do sexo masculino. A duração mediana de internação foi 15,4 (2-92) dias e sete (14,6%) pacientes morreram. Um total de 70 ecocardiografias foram realizadas, 66,7% submeteram-se ao exame somente uma vez, e 33,3% várias vezes. Vinte e três (48%) pacientes apresentaram anormalidades no ecocardiograma: oito (16.6%) disfunção sistólica do ventrículo esquerdo, seis (12.5%) disfunção sistólica do ventrículo direito, e 12 (25%) dilatação da artéria coronária (Z-score>+2,5). Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, admissão na unidade de terapia intensiva pediátrica, suporte ventilatório/vasoativo, e morte ( p <0,05). Níveis significativamente mais altos de d-dímero (ng/mL) foram detectados em pacientes com disfunção ventricular esquerda [16733(4157-115668) vs. 2406.5(190-95040)], disfunção ventricular direita [25769(3422-115668) vs. 2803.5(190-95040)] e dilatação da artéria coronária [9652.5(921-115668) vs. 2724(190- 95040)] (p<0,05). Conclusão Anormalidades ecocardiográficas eram frequentes nos pacientes pediátricos com COVID-19 e associadas com piores desfechos clínicos. Exacerbação das vias de inflamação e coagulação pode exercer um importante papel na lesão cardiovascular nesses pacientes.

Abstract Background COVID-19 pandemic represents a huge burden to the health system in the world. Although pediatric COVID-19 patients have been relatively spared compared with adults, recent reports showed an increasing number of critically ill patients with multisystemic inflammatory syndrome in children (MIS-c), with marked cardiovascular impairment. Nevertheless, little is known about the relationship between cardiac abnormalities and inflammatory and coagulation biomarkers. Objectives to investigate echocardiographic abnormalities in pediatric patients with COVID-19 admitted to tertiary hospital. Methods this was a retrospective longitudinal study, based on the review of medical records and echocardiograms of patients (0-19 years) admitted to a tertiary hospital between March 30 and June 30, 2020. For statistical analysis, the significance level was set at 5% (p < 0.05). Results Forty-eight patients were enrolled, 73% with preexisting diseases, 20 (41.7%) with MIS-c. Median age was 7.5 (0-18.6) years; 27 (56.2%) were male. Median duration of hospitalization was 15.4 (2-92) days and seven (14.6%) patients died. A total of 70 echocardiograms were performed; 66.7% patients were scanned only once and 33.3% multiple times. Twenty-three (48%) patients showed echocardiographic abnormalities: eight (16.6%) left ventricle (LV) systolic dysfunction, six (12.5%) right ventricle (RV) systolic dysfunction and 12 (25%) coronary dilatation (Z-score>+2.5). Echocardiographic abnormalities were significantly associated with MIS-c, admission to the pediatric intensive care unit, multiple organ dysfunction, ventilatory/vasoactive support, and death (p<0.05). Significantly higher d-dimer (ng/mL) levels were detected in patients with LV dysfunction [16733(4157-115668) vs. 2406.5(190-95040)], RV dysfunction [25769(3422-115668) vs. 2803.5(190-95040)] and coronary artery dilation [9652.5(921-115668) vs. 2724(190- 95040)] (p<0.05). Conclusion Echocardiographic abnormalities in COVID-19 pediatric patients were frequent and associated with worse clinical outcomes. Exacerbation of the inflammation and coagulation pathways may play an important role in cardiovascular injury in those patients.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Changing the view: Video versus direct laryngoscopy for intubation in the pediatric emergency department.

The aim of this study was to compare the success of first-attempt tracheal intubation in pediatric patients >1-year old performed using video versus direct laryngoscopy and compare the frequency of tracheal intubation-associated events and desaturation among these patients.Prospective observational cohort study conducted in an Academic pediatric tertiary emergency department. We compared 50 children intubated with Mcgrath Mac video laryngoscope (VL group) and an historical series of 141 children intubated with direct laryngoscopy (DL group). All patients were aged 1 to 18 years.The first attempt success rates were 68% (34/50) and 37.6% (53/141) in the VL and DL groups (P < .01), respectively. There was a lower proportion of tracheal intubation-associated events in the VL group (VL, 31.3% [15/50] vs DL, 67.8% [97/141]; P < .01) and no significant differences in desaturation (VL, 35% [14/50] vs DL 51.8% [72/141]; P = .06). The median number of attempts was 1 (range, 1-5) for the VL group and 2 (range, 1-8) for the DL group (P < .01). Multivariate logistic regression showed that video laryngoscope use was associated with higher chances of first-attempt intubation with an odds ratio of 4.5 (95% confidence interval, 1.9-10.4, P < 0.01).Compared with direct laryngoscopy, VL was associated with higher success rates of first-attempt tracheal intubations and lower rates of tracheal intubation-associated events.

Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial.

BACKGROUND: The Butantan Institute has manufactured a lyophilised tetravalent live-attenuated dengue vaccine Butantan-DV, which is analogous to the US National Institutes of Health (NIH) TV003 admixture. We aimed to assess the safety and immunogenicity of Butantan-DV. METHODS: We did a two-step, double-blind, randomised placebo-controlled phase 2 trial at two clinical sites in São Paulo, Brazil. We recruited healthy volunteers aged 18-59 years; pregnant women, individuals with a history of neurological, heart, lung, liver or kidney disease, diabetes, cancer, or autoimmune diseases, and individuals with HIV or hepatitis C were excluded. Step A was designed as a small bridge-study between Butantan-DV and TV003 in DENV-naive participants. In step A, we planned to randomly assign 50 dengue virus (DENV)-naive individuals to receive two doses of Butantan-DV, TV003, or placebo, given 6 months apart. In step B, we planned to randomly assign 250 participants (DENV-naive and DENV-exposed) to receive one dose of Butantan-DV or placebo. Participants were randomly assigned, by computer-generated block randomisation (block sizes of five); participants in step A were randomly assigned (2:2:1) to receive Butantan-DV, TV003, or placebo and participants in step B were randomly assigned (4:1) to receive Butantan-DV or placebo. Participants and study staff were unaware of treatment allocation. The primary safety outcome was the frequency of solicited and unsolicited local and systemic adverse reactions within 21 days of the first vaccination, analysed by intention to treat. The primary immunogenicity outcome was seroconversion rates of the DENV-1-4 serotypes measured 91 days after the first vaccination, analysed in the per-protocol population, which included all participants in step A, and all participants included in step B who completed all study visits with serology sample collection. This trial is registered with ClinicalTrials.gov, NCT01696422. FINDINGS: Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received placebo. Butantan-DV and TV003 were both immunogenic, well-tolerated, and no serious adverse reactions were observed. In step A, rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4. INTERPRETATION: Butantan-DV and TV003 were safe and induced robust, balanced neutralising antibody responses against the four DENV serotypes. Efficacy evaluation of the Butantan-DV vaccine is ongoing. FUNDING: Intramural Research Program US NIH National Institute of Allergy and Infectious Diseases, Brazilian National Bank for Economic and Social Development, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Fundação Butantan.

Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome

OBJECTIVES: To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). METHODS: This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control. RESULTS: MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p<0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p<0.001), vasoactive agent use (83% vs. 3%, p<0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p<0.001), and death (67% vs. 3%, p<0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p<0.001), aspirin therapy (50% vs. 0%, p<0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39-526.79; p<0.0001]. CONCLUSIONS: Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.

Risk Factors Associated with Juvenile Idiopathic Arthritis: Exposure to Cigarette Smoke and Air Pollution from Pregnancy to Disease Diagnosis.

OBJECTIVE: To evaluate exposure to environmental factors inhaled during pregnancy and after birth until juvenile idiopathic arthritis (JIA) diagnosis among residents of a large city. METHODS: This is an exploratory case-control study that consists of 66 patients with JIA and 124 healthy controls matched by age and sex, living in the São Paulo, Brazil, metropolitan area until JIA diagnosis, and whose mothers had resided in this region during pregnancy. A structured and reliable questionnaire (κ index for test-retest was 0.80) assessed demographic data, gestational and perinatal-related factors, and exposure to inhalable environmental elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, exposure to cigarette smoke, and the presence of industrial activities or gas stations near the home, work, daycare, or school). Tropospheric pollutants included particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO). RESULTS: During pregnancy, intrauterine cigarette smoke exposure (OR 3.43, 95% CI 1.45-8.12, p = 0.005) and maternal occupational exposure (OR 13.69, 95% CI 4.4-42.3, p < 0.001) were significant independent risk factors for JIA diagnosis. In contrast, maternal employment (OR 0.06, 95% CI 0.02-0.2, p < 0.001) and ideal maternal weight gain (OR 0.36, 95% CI 0.2-0.8, p = 0.017) presented negative associations. Secondhand smoke exposure from birth to JIA diagnosis (OR 3.6, 95% CI 1.8-7.3, p < 0.001) and exposure to O3 during the second year of life (OR 2.76, 95% CI 1.20-6.37, p = 0.017) were independent and significant risk factors for the pathogenesis of JIA. CONCLUSION: In our study, cigarette smoke exposure (intrauterine and after birth), exposure to O3 in the second year of life, and maternal occupational exposure were identified as potential risk factors for JIA, warranting further study.

Influence of air pollution on airway inflammation and disease activity in childhood-systemic lupus erythematosus.

Exposure to fine particles may trigger pulmonary inflammation/systemic inflammation. The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus (cSLE) patients. A longitudinal panel study was carried out in 108 consecutive appointments with cSLE patients without respiratory diseases. Over four consecutive weeks, daily individual measures of nitrogen dioxide (NO2), fine particulate matter (PM2.5), ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate-EBC [interleukins (IL) 6, 8, 17 and tumoral necrose factor-α (TNF-α)], fractional exhaled NO (FeNO), and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 (SLEDAI-2K) ≥ 8, EBC cytokines, and FeNO, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. An IQR increase in PM2.5 4-day moving average (18.12 µg/m3) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in IL-17 and TNF-α EBC levels, respectively. Additionally, a short-term effect on FeNO was observed: the PM2.5 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in FeNO. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of SLEDAI-2K ≥ 8 was associated with PM2.5 7-day moving average. Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in cSLE patients.

Ozone decreases sperm quality in systemic lupus erythematosus patients / O ozônio diminui a qualidade do sêmen em pacientes com lúpus eritematoso sistêmico

Abstract Objective To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). Methods A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. Results Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01–89.65; p = 0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93–216.38; p = 0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80–88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8–40.0; p = 0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3–128.7; p = 0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80–88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0–53.0; p = 0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1–155.9; p = 0.044). Conclusion Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities.

Resumo Objetivo Investigar os efeitos deletérios da exposição aos poluentes do ar na Região Metropolitana de São Paulo sobre a qualidade do sêmen de pacientes com lúpus eritematoso sistêmico (LES). Métodos Foi feito um estudo longitudinal de painel com medidas repetidas de sete anos no Laboratório de Poluição Atmosférica Experimental e Reumatologia. Foram analisadas duas amostras de sêmen de 28 pacientes com LES pós‐púberes. Foram avaliadas as concentrações diárias de exposição aos poluentes do ar PM10, SO2, NO2, ozônio e CO e variáveis meteorológicas 90 dias antes de cada data de coleta de sêmen com o uso do método de equações de estimativas generalizadas. Resultados A ciclofosfamida intravenosa (CICIV) e o ozônio estiveram associados a uma diminuição na qualidade do sêmen dos pacientes com LES. A CICIV esteve associada a um decréscimo de 64,3 milhões de espermatozoides/mL (IC 95% 39,01‐89,65; p = 0,0001) e 149,14 milhões de espermatozoides/ejaculado (IC 95% 81,93‐216,38; p = 0,017). Em relação ao ozônio, os efeitos adversos mais relevantes foram observados entre os lags (intervalo de tempo) 80 e 88, quando a exposição a uma concentração média de ozônio um intervalo interquartil maior em nove dias móveis levou a um decréscimo de 22,9 milhões de espermatozoides/mL (IC 95% 5,8‐40; p = 0,009) e 70,5 milhões de espermatozoides/ejaculado (IC 95% 12,3‐128,7; p = 0,016). Uma análise mais aprofundada dos 17 pacientes que nunca usaram CICIV mostrou associação entre a exposição ao ozônio (80‐88 dias) e o decréscimo de 30 milhões de espermatozoides/mL (IC 95% 7‐53; p = 0,011) e 79 milhões de espermatozoides/ejaculado (IC 95% 2,1‐155,9; p = 0,044). Conclusão O ozônio e a CICIV tiveram um efeito adverso consistente sobre a qualidade do sêmen de pacientes com LES durante a espermatogênese. Deve‐se considerar a minimização da exposição à poluição do ar, especialmente para pacientes com doenças inflamatórias sistêmicas crônicas que vivem nas grandes cidades.

Air pollution and children's health: sickle cell disease / Poluição do ar e a saúde das crianças: a doença falciforme / Contaminación atmosférica y salud de los niños: la enfermedad de células falciformes

The hallmarks of sickle cell disease are anemia and vasculopathy. The aim of this study was to assess the association between air pollution and children's emergency room visits of sickle cell patients. We adopted a case-crossover design. Daily counts of children's and adolescents' sickle cell disease emergency room visits from the pediatric emergency unit in São Paulo, Brazil, were evaluated from September 1999 to December 2004, matching by temperature, humidity and controlling for day of the week. Interquartile range increases of the four-day moving averages of PM10, NO2, SO2, CO, and O3 were associated with increases of 18.9% (95%CI: 11.2-26.5), 19% (95%CI: 8.3-29.6), 14.4% (95%CI: 6.5-22.4), 16,5% (95%CI: 8.9-24.0), and 9.8% (95%CI: 1.1-18.6) in total sickle cell emergency room visits, respectively. When the analyses were stratified by pain, PM10 was found to be 40.3% higher than in sickle cell patients without pain symptoms. Exposure to air pollution can affect the cardiovascular health of children and may promote a significant health burden in a sensitive group.

O objetivo deste estudo foi avaliar a associação entre a poluição do ar e atendimentos de emergência pediátrica de pacientes portadores de anemia falciforme. Adotamos um estudo de case-crossover. Visitas de crianças e adolescentes portadores de anemia falciforme ao pronto-socorro pediátrico, em São Paulo, Brasil, foram avaliadas a partir de setembro de 1999 até dezembro de 2004, controlando a temperatura, umidade e dia da semana. Variações interquartis das médias móveis de quatro dias de PM10, NO2, SO2, CO e O3 foram associadas com aumentos de 18,9% (IC95%: 11,2-26,5), 19% (IC95%: 8,3-29,6), 14,4% (IC95%: 6,5-22,4), 16,5% (IC95%: 8,9-24,0) e 9,8% (IC95%: 1,1-18,6) nos atendimentos totais, respectivamente. Quando as análises foram estratificadas por dor, verificou-se que PM10 apresentou correlação 40,3% maior do que a observada em pacientes falciformes sem sintomas de dor. A exposição à poluição do ar pode afetar a saúde cardiovascular de crianças e promover um fardo significativo para a saúde em um grupo suscetível, como o de pacientes com anemia falciforme.

El objetivo de este estudio fue evaluar la asociación entre la contaminación atmosférica y las visitas de emergencia de los pacientes pediátricos con anemia de células falciformes. Hemos adoptado un estudio de casos cruzados. Visitas de niños y adolescentes con anemia de células falciformes en urgencias pediátricas, en São Paulo, Brasil, se evaluaron entre 1999 y 2004 con un control de la temperatura, humedad y día de la semana. El rango intercuartil de los promedios móviles de 4 días de PM10, NO2, SO2, CO y O3 se asociaron con un aumento del 18,9% (IC95%: 11,2-26,5), 19,0% (IC95%: 8,3-29,6), 14,4% (IC95%: 6,5-22,4), 16,5% (IC95%: 8,9-24,0), y 9,8% (IC95%: 1,1-18,6) en el total de visitas, respectivamente. Cuando los análisis se estratificaron por el dolor, se encontró que el PM10 mostró una correlación un 40,3% mayor que la observada en pacientes sin síntomas de dolor. La exposición a la contaminación del aire puede afectar la salud cardiovascular de los niños y puede promover una importante carga para la salud en pacientes con anemia de células falciformes.

Mortalidade em hospital secundário pediátrico na Libéria pós-conflito em 2009 / Mortality in a pediatric secondary-care hospital in post-conflict Liberia in 2009

OBJETIVO: Descrever e analisar as causas de morte em um hospital secundário pediátrico (administrado pelos Médicos sem Fronteiras) na Monróvia, Libéria, 6 anos após o fim da guerra civil, para determinar a qualidade dos cuidados e a mortalidade em uma realidade com recursos limitados. MÉTODOS: Os dados foram coletados retrospectivamente de março a outubro de 2009. Os prontuários e dados laboratoriais foram revisados para verificar a causa de morte. Além disso, prontuários de pacientes com mais de 1 mês de vida com causa de morte infecciosa foram analisados, para avaliar a presença de choque séptico descompensado ou choque séptico refratário a fluidos. RESULTADOS: Do total de 8.254 pacientes admitidos, 531 morreram, com taxa de mortalidade de 6,4%. Noventa por cento dos óbitos ocorreram em crianças <5 anos. A maioria das mortes ocorreu nas primeiras 24 horas de internação. A causa principal (76%) foi doença infecciosa. Apresentaram choque séptico 78 (23,6%) pacientes com mais de 1 mês de idade e doença infecciosa, e 28 (8,6%) apresentaram choque séptico descompensado ou refratário a fluidos. CONCLUSÃO: Desde o fim da devastadora guerra civil na Libéria, o Island Hospital tem melhorado a qualidade de cuidado e diminuído a taxa de mortalidade, apesar de atuar com recursos limitados. Com base nos dados disponíveis, a mortalidade do Island Hospital aparenta ser menor do que em outras instituições liberianas e africanas, e semelhante a de outros hospitais administrados pelos Médicos sem Fronteiras na África. A explicação para esse fato é o apoio logístico e financeiro dos Médicos sem Fronteiras. A maior carga de mortalidade está relacionada a doenças infecciosas e condições neonatais. A mortalidade por sepse variou entre diferentes infecções. Isso sugere que a mortalidade ainda pode ser reduzida ao se melhorarem o tratamento e os cuidados neonatais.

OBJECTIVE: To describe and analyze the causes of death in a pediatric secondary-care hospital (run by Médecins sans Frontières), in Monrovia, Liberia, 6 years post-civil war, to determine the quality of care and mortality in a setting with limited resources. METHODS: Data were retrospectively collected from March 2009 to October 2009. Patient charts and laboratory records were reviewed to verify cause of death. Additionally, charts of patients aged over 1 month with an infectious cause of death were analyzed for decompensated septic shock, or fluid-refractory septic shock. RESULTS: Of 8,254 admitted pediatric patients, 531 died, with a mortality rate of 6.4%. Ninety percent of deaths occurred in children <5 years old. Most deaths occurred within 24 hours of admission. The main cause of death (76%) was infectious disease. Seventy-eight (23.6%) patients >1 month old with infectious disease met the criteria for septic shock, and 28 (8.6%) for decompensated or fluid-refractory septic shock. CONCLUSION: Since the end of Liberia's devastating civil war, Island Hospital has improved care and mortality outcomes, despite operating with limited resources. Based on the available data, mortality in Island Hospital appears to be lower than that of other Liberian and African institutions and similar to other hospitals run by Médecins sans Frontières across Africa. This can be explained by the financial and logistic support of Médecins sans Frontières. The highest mortality burden is related to infectious diseases and neonatal conditions. The mortality of sepsis varied among different infections. This suggests that further mortality reduction can be obtained by tackling sepsis management and improving neonatal care.

Parental smoking patterns and their association with wheezing in children.

OBJECTIVE: To investigate parental smoking patterns and their association with wheezing in children. METHODS: We performed a case-control study that included 105 children between 6 and 23 months of age who were divided into two groups: cases (children with 3 previous episodes of wheezing) and controls (healthy children without wheezing). The children's exposure to cigarette smoking was estimated using a questionnaire completed by the mothers and by the children's urinary cotinine levels. RESULTS: Based on both the questionnaire results and cotinine levels, exposure to cigarette smoking was higher in the households of cases in which the incidence of maternal smoking was significantly higher than that of paternal smoking. Children in this group were more affected by maternal smoking and by the total number of cigarettes smoked inside the house. Additionally, the questionnaire results indicated that the risk of wheezing was dose dependent. The presence of allergic components, such as atopic dermatitis and siblings with allergic rhinitis and asthma, greatly increased the odds ratio when wheezing was associated with cotinine levels. CONCLUSION: Children exposed to tobacco smoke have an increased risk of developing wheezing syndrome. This risk increases in association with the number of cigarettes smoked inside the house and the presence of other allergic components in the family.

Parental smoking patterns and their association with wheezing in children

OBJECTIVE: To investigate parental smoking patterns and their association with wheezing in children. METHODS: We performed a case-control study that included 105 children between 6 and 23 months of age who were divided into two groups: cases (children with 3 previous episodes of wheezing) and controls (healthy children without wheezing). The children's exposure to cigarette smoking was estimated using a questionnaire completed by the mothers and by the children's urinary cotinine levels. RESULTS: Based on both the questionnaire results and cotinine levels, exposure to cigarette smoking was higher in the households of cases in which the incidence of maternal smoking was significantly higher than that of paternal smoking. Children in this group were more affected by maternal smoking and by the total number of cigarettes smoked inside the house. Additionally, the questionnaire results indicated that the risk of wheezing was dose dependent. The presence of allergic components, such as atopic dermatitis and siblings with allergic rhinitis and asthma, greatly increased the odds ratio when wheezing was associated with cotinine levels. CONCLUSION: Children exposed to tobacco smoke have an increased risk of developing wheezing syndrome. This risk increases in association with the number of cigarettes smoked inside the house and the presence of other allergic components in the family. .