Treatments for multi-system inflammatory syndrome in children - discharge, fever, and second-line therapies.

Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p = 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p = 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43-13.5, p = 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05-9.82, p < 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.    Conclusions: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment. What is Known: • Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low. What is New: • Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes. • In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.

Integrase inhibitors in children and adolescents: clinical use and resistance.

BACKGROUND: Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART. METHODS: Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts. Resistance mutations were identified by the Stanford HIV Drug Resistance Database. RESULTS: Overall, 318 INI-based regimens were implemented in 288 patients [53.8% female; median age at start of 14.3 years (IQR 12.0-16.3)]. Most were born in Spain (69.1%), vertically infected (87.7%) and treatment-experienced (92.7%). The most frequently prescribed INI was dolutegravir (134; 42.1%), followed by raltegravir (110; 34.6%) and elvitegravir (73; 23.0%). The median exposure was 2.0 years (IQR 1.1-3.0). The main reasons to start an INI-based therapy were treatment simplification (54.4%) and virological failure (34.3%). In total, 103 (32.4%) patients interrupted their regimen: 14.5% for simplification and 8.5% due to virological failure. Most subjects who received dolutegravir (85.8%) and elvitegravir (83.6%) did not interrupt their regimen and maintained undetectable viral load. There were only five virological failures with dolutegravir and three with elvitegravir. There were no interruptions related to adverse events. Seven patients with virological failure presented major resistance mutations to INIs; none of them were on dolutegravir. CONCLUSIONS: INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.

Innovative strategies for the surveillance, prevention, and management of pediatric infections applied to low-income settings.

INTRODUCTION: Infectious diseases still cause a significant burden of morbidity and mortality among children in low- and middle-income countries (LMICs). There are ample opportunities for innovation in surveillance, prevention, and management, with the ultimate goal of improving survival. AREAS COVERED: This review discusses the current status in the use and development of innovative strategies for pediatric infectious diseases in LMICs by focusing on surveillance, diagnosis, prevention, and management. Topics covered are: Minimally Invasive Tissue Sampling as a technique to accurately ascertain the cause of death; Genetic Surveillance to trace the pathogen genomic diversity and emergence of resistance; Artificial Intelligence as a multidisciplinary tool; Portable noninvasive imaging methods; and Prognostic Biomarkers to triage and risk stratify pediatric patients. EXPERT OPINION: To overcome the specific hurdles in child health for LMICs, some innovative strategies appear at the forefront of research. If the development of these next-generation tools remains focused on accessibility, sustainability and capacity building, reshaping epidemiological surveillance, diagnosis, and treatment in LMICs, can become a reality and result in a significant public health impact. Their integration with existing healthcare infrastructures may revolutionize disease detection and surveillance, and improve child health and survival.

Burden of child mortality from malaria in high endemic areas: Results from the CHAMPS network using minimally invasive tissue sampling.

BACKGROUND: Malaria is a leading cause of childhood mortality worldwide. However, accurate estimates of malaria prevalence and causality among patients who die at the country level are lacking due to the limited specificity of diagnostic tools used to attribute etiologies. Accurate estimates are crucial for prioritizing interventions and resources aimed at reducing malaria-related mortality. METHODS: Seven Child Health and Mortality Prevention Surveillance (CHAMPS) Network sites collected comprehensive data on stillbirths and children <5 years, using minimally invasive tissue sampling (MITS). A DeCoDe (Determination of Cause of Death) panel employed standardized protocols for assigning underlying, intermediate, and immediate causes of death, integrating sociodemographic, clinical, laboratory (including extensive microbiology, histopathology, and malaria testing), and verbal autopsy data. Analyses were conducted to ascertain the strength of evidence for cause of death (CoD), describe factors associated with malaria-related deaths, estimate malaria-specific mortality, and assess the proportion of preventable deaths. FINDINGS: Between December 3, 2016, and December 31, 2022, 2673 deaths underwent MITS and had a CoD attributed from four CHAMPS sites with at least 1 malaria-attributed death. No malaria-attributable deaths were documented among 891 stillbirths or 924 neonatal deaths, therefore this analysis concentrates on the remaining 858 deaths among children aged 1-59 months. Malaria was in the causal chain for 42.9% (126/294) of deaths from Sierra Leone, 31.4% (96/306) in Kenya, 18.2% (36/198) in Mozambique, 6.7% (4/60) in Mali, and 0.3% (1/292) in South Africa. Compared to non-malaria related deaths, malaria-related deaths skewed towards older infants and children (p < 0.001), with 71.0% among ages 12-59 months. Malaria was the sole infecting pathogen in 184 (70.2%) of malaria-attributed deaths, whereas bacterial and viral co-infections were identified in the causal pathway in 24·0% and 12.2% of cases, respectively. Malnutrition was found at a similar level in the causal pathway of both malaria (26.7%) and non-malaria (30.7%, p = 0.256) deaths. Less than two-thirds (164/262; 62.6%) of malaria deaths had received antimalarials prior to death. Nearly all (98·9%) malaria-related deaths were deemed preventable. INTERPRETATION: Malaria remains a significant cause of childhood mortality in the CHAMPS malaria-endemic sites. The high bacterial co-infection prevalence among malaria deaths underscores the potential benefits of antibiotics for severe malaria patients. Compared to non-malaria deaths, many of malaria-attributed deaths are preventable through accessible malaria control measures.

Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months.

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted.

IgA deficiency and autoimmune comorbidities in Juvenile Idiopathic Arthritis.

OBJECTIVES: (1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and, (2) to evaluate whether patients with JIA and IgAD present other autoimmune diseases more frequently than patients with normal serum levels of IgA. METHODS: Retrospective chart review of a cohort of patients diagnosed with JIA followed at the paediatric rheumatology units of two hospitals in Madrid, Spain. RESULTS: A total of 193 patients were included. Of them, 123 were females (64%). Median age at disease onset was 5.6 years (IQR 2.5-9.7) and the median time of follow-up was 5.1 years (IQR 2.2-8.1). The three most common ILAR categories were oligoarticular (53%), polyarticular RF negative (20%) and enthesitis related arthritis (10%). Serum IgA levels were available in 172/193 (89%); 25/172 (15%) had selective (<7mg/dl, n=8) or partial (7-69mg/dl, n=17) IgAD. All the patients had periodic eye exams. Eighteen children (9%) had anterior uveitis, 15/18 chronic and 3/18 acute. Serum anti transglutaminase IgA, or IgG in IgAD were obtained in 135/193 (70%). Four children (3%) were diagnosed with CD either by intestinal biopsy (n=3) or by the combination of characteristic clinical, serological and genetic features (n=1); two of them had IgAD (p=0.12; OR=6.4; 95% CI 0.9-47.6). Only 1/153 (0.7%) patient had hyperthyrotropinemia with positive anti-thyroid antibodies and required replacement therapy. CONCLUSION: Patients with JIA frequently present autoimmune comorbidities. IgAD does not seem to increase their prevalence, with the possible exception of CD.

Rituximab as Second-Line Treatment in Anti-NMDAR Encephalitis after Herpes Simplex Encephalitis in Children.

The long-term response of two infants with anti-N-methyl-D-aspartate receptor (anti-NMDAR) post herpes simplex encephalitis treated with rituximab is reported here. Rituximab may improve the course of the disease and should be considered early as second-line treatment. Data on the long-term effect of rituximab in B cell depletion and immunoglobulins levels in infants are needed.

Acute bronchiolitis and respiratory syncytial virus seasonal transmission during the COVID-19 pandemic in Spain: A national perspective from the pediatric Spanish Society (AEP).

INTRODUCTION AND OBJECTIVES: The COVID-19 pandemic and the widespread associated use of non-pharmaceutical interventions have impacted viral circulation and the incidence of respiratory tract infections. We compared Pediatric Emergency Department visits, bronchiolitis admissions, and respiratory syncytial virus (RSV) cases in 2020 with those documented for the preceding four years. METHODS: This was a retrospective multicentric national survey study, driven by the Pediatric Spanish Society, and gathering monthly data from Spanish hospitals between 1st January 2016 and 31st December 2020. An Interrupted Time Series Analysis and Poisson regression models were performed for each index. RESULTS: Thirty-eight hospitals representing most of the different regions of Spain participated. Compared to the preceding four years, in 2020, Pediatric emergency department visits significantly decreased immediately after initiation of the national lockdown. The median number of visits averted per month was 39,754 (IQR 26,539-50,065). RSV diagnoses during the 2020 winter season nearly disappeared with only 21 cases being documented among participating hospitals. The expected seasonal peak of bronchiolitis hospitalizations never occurred. The median number of admissions in 2020 averted per month was 100 (IQR 37-185) compared to 2016-2019. Only 3 hospitalized cases were RSV-confirmed. Reopening of schools and kindergarten was not associated with a remarkable increase in RSV cases or bronchiolitis hospitalizations. CONCLUSION: A dramatic reduction of bronchiolitis admissions and near disappearance of RSV cases was observed in Spanish hospitals coinciding with the peak of the COVID-19 pandemic.

Etiology and outcome of febrile children coming from the tropics.

INTRODUCTION: International travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. METHODS: Retrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. RESULTS: 188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5-8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. CONCLUSION: Children with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Etiology and outcome of febrile children coming from the tropics.

INTRODUCTION: International travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. METHODS: Retrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. RESULTS: 188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5-8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. CONCLUSION: Children with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Severe Rifampicin-induced Vitamin K Deficiency Coagulopathy in a Child.

An 8-month-old child under tuberculosis treatment presented with multiple ecchymotic lesions. A severe coagulopathy was evidenced compatible with vitamin K deficiency [II (3%), VII (2%), IX (3%) and X (1%)]. It was reversed with vitamin K and plasma administration. Rifampicin-induced vitamin K deficiency is very rare, reported only once before, possibly related to an inhibition of vitamin K cycle.

Cross-cultural consistency and relativity in the enjoyment of thinking versus doing.

Which is more enjoyable: trying to think enjoyable thoughts or doing everyday solitary activities? Wilson et al. (2014) found that American participants much preferred solitary everyday activities, such as reading or watching TV, to thinking for pleasure. To see whether this preference generalized outside of the United States, we replicated the study with 2,557 participants from 12 sites in 11 countries. The results were consistent in every country: Participants randomly assigned to do something reported significantly greater enjoyment than did participants randomly assigned to think for pleasure. Although we found systematic differences by country in how much participants enjoyed thinking for pleasure, we used a series of nested structural equation models to show that these differences were fully accounted for by country-level variation in 5 individual differences, 4 of which were positively correlated with thinking for pleasure (need for cognition, openness to experience, meditation experience, and initial positive affect) and 1 of which was negatively correlated (reported phone usage). (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Recepción de series televisivas y formación de esquemas cognoscitivos asociados a sus personajes: un estudio con niños y adolescentes costarricenses / Reception of Television Series and Formation of Cognitive Schemas Associated to their Characters: A Study of Costa Rican Children and Adolescents

El estudio indaga la asociación entre el visionado televisivo, específicamente la intensidad de uso de la televisión y la valoración de series de televisión, en la formación de esquemas de personas. Compara la organización categorial ante una serie de televisión en un grupo de niños, niñas y adolescentes. Se estudiaron variables cognoscitivas y psicomediáticas, como variables intervinientes. Los resultados muestran diferencias entre los grupos de edad con respecto a la accesibilidad y variabilidad del contenido de los esquemas y la participación diferencial de las variables cognoscitivas y psicomediáticas. Se discuten sus implicaciones para el estudio de la comprensión del mensaje televisivo, específicamente de las series televisivas, y para el desarrollo de las competencias para la recepción televisiva.

The study inquires the association between television viewing, specifically television use intensity and TV series evaluation on the formation of person schemata. It compares categorical organization among a group of children and adolescents facing a TV series. As intervening variables are studied cognitive and media psychological variables. Results show age differences concerning accessibility and variability of schemata content and differential participation of cognitive and media psychological variables. Implications for the study of the comprehension of TV series and for the development of competences for TV reception are discussed.