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INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. METHODS AND ANALYSIS: This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification crit

BACKGROUND: Colistin serves as the last line of defense against multidrug resistant Gram-negative bacterial infections in both human and veterinary medicine. This study aimed to investigate the occurrence and spread of colistin-resistant Enterobacterales (ColR-E) using a One Health approach in Belgium and in the Netherlands.METHODS: In a transnational research project, a total of 998 hospitalized patients, 1430 long-term care facility (LTCF) residents, 947 children attending day care centres, 1597 pigs and 1691 broilers were sampled for the presence of ColR-E in 2017 and 2018, followed by a second round twelve months later for hospitalized patients and animals. Colistin treatment incidence in livestock farms was used to determine the association between colistin use and resistance. Selective cultures and colistin minimum inhibitory concentrations (MIC) were employed to identify ColR-E. A combination of short-read and long-read sequencing was utilized to investigate the molecular characteristics of 562 colistin-resistant isolates. Core genome multi-locus sequence typing (cgMLST) was applied to examine potential transmission events.RESULTS: The presence of ColR-E was observed in all One Health sectors. In Dutch hospitalized patients, ColR-E proportions (11.3 and 11.8% in both measurements) were higher than in Belgian patients (4.4 and 7.9% in both measurements), while the occurrence of ColR-E in Belgian LTCF residents (10.2%) and children in day care centres (17.6%) was higher than in their Dutch counterparts (5.6% and 12.8%, respectively). Colistin use in pig farms was associated with the occurrence of colistin resistance. The percentage of pigs carrying ColR-E was 21.8 and 23.3% in Belgium and 14.6% and 8.9% in the Netherlands during both measurements. The proportion of broilers carrying ColR-E in the Netherlands (5.3 and 1.5%) was higher compared to Belgium (1.5 and 0.7%) in both measurements. mcr-harboring E. coli were detected in 17.4% (31/178) o

A neurocysticercosis-like lesion in an 11-year-old boy in the Netherlands was determined to be caused by the zoonotic Taenia martis tapeworm. Subsequent testing revealed that 15% of wild martens tested in that region were infected with T. martis tapeworms with 100% genetic similarity; thus, the infection source was most likely local.

OBJECTIVE: We evaluated the uptake of medicines licensed as orphan drugs by the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) into the WHO Model list of essential medicines and the WHO Model list of essential medicines for children from 1977 to 2021. METHODS: We collated and analysed data on drug characteristics, reasons for adding or rejecting medicines, and time between regulatory approval and inclusion in the lists. We compared trends in listing orphan drugs before and after revisions to the inclusion criteria of the essential medicines lists in 2001, as well as differences in trends for listing orphan and non-orphan drugs, respectively.FINDINGS: The proportion of orphan drugs in the essential medicines lists increased from 1.9% (4/208) in 1977 to 14.6% (70/478) in 2021. While orphan drugs for communicable diseases have remained stable over time, we observed a considerable shift towards more orphan drugs for noncommunicable diseases, particularly for cancer. The median period for inclusion in the essential medicines lists after either FDA or EMA first approval was 13.5 years (range: 1-28 years). Limited clinical evidence base and uncertainty about the magnitude of net benefit were the most frequent reasons to reject proposals to add new orphan drugs to the essential medicines lists.CONCLUSION: Despite lack of a global definition of rare diseases, the essential medicines lists have broadened their scope to include medicines for rare conditions. However, the high costs of many listed orphan drugs pose accessibility and reimbursement challenges in resource-constrained settings.

Purpose: This study explores limitations in communication in daily life of children with developmental language disorder (DLD) from their parents' perspective as well as communicative abilities and social functioning in the classroom from their teacher's perspective. Furthermore, differences between children with mixed receptive–expressive disorder and children with expressive-only disorder in communication in daily life and social functioning are studied. Method: Data were collected through questionnaires completed by parents and teachers of children (5–6 years old) who attended schools for special education for DLD. Language test scores were retrieved from school records. Parents of 60 children answered open-ended questions about situations and circumstances in which their child was most troubled by language difficulties. Teachers of 83 children rated communicative abilities, social competence, and student–teacher relationship. Results: Parents reported communication with strangers as most troublesome and mentioned the influence of the mental state of their child. Parents considered limitations in expressing oneself and being understood and not being intelligible as core difficulties. Teachers rated the children's communicative abilities in the school context as inadequate, but their scores concerning social competence and the quality of teacher–child relationships fell within the normal range. Children with receptive–expressive disorder experienced limitations in communication in almost all situations, whereas those with expressive disorder faced limitations in specific situations. Children with receptive–expressive disorder were also significantly more limited in their communicative abilities and social competence at school than children with expressive disorder. No differences were found between the two groups in the quality of the teacher–child relationship. Conclusions: The results confirm that children with DLD face significant challenges in a va

The aim of this literature study was to examine the evidence of family therapy and familybased interventions for children and adolescents with depression. Additionally, this study highlights how different research perspectives and outcome measures may affect the recommendations of treatment interventions. Nine articles were reviewed and assessed for their scientific quality. Five of the articles were randomized controlled studies (RCTs) and four studies were of a different design (non-RCTs). The overall results of the studies showed that family therapy or family-based interventions reduce depression symptoms. When compared to other treatments (not all studies included comparison with other treatments) the intervention reduced the depression symptoms equivalently to other treatments and in some cases more effectively. Positive side effects on comorbidity as well as familial and environmental factors were also shown in some of the studies. Given the variety and the modest overall quality of the studies some of the results should be interpreted with great caution. Similar results are supported in some meta-analyses but questioned in others. The conclusion of this literature study was that there is evidence to support the recommendation and choice of family therapy in the treatment of depression in children and adolescents on the basis of the Evidence Based Practise (EBP) perspective when taking efficacy, effectiveness and efficiency in consideration. More family therapy studies of higher quality and on the basis of EBP are needed measuring other domains than symptoms of the primary diagnosis. Manualizing family therapy methods or conceptualizing common factors may be an important step forward to identify the specific mechanisms of change in evidence and to be able to generalize them., Syftet med denna litteraturstudie var att undersöka det vetenskapliga stödet for familjeterapi och familjebaserade interventioner vid behandling för depression hos barn och ungdomar. Dessutom ville vi belysa hur olika forskningsperspektiv och utfallsmått kan påverka rekommendationerna för val av behandling. Nio artiklar undersöktes och bedömdes efter dess vetenskapliga kvalitet. Fem av artiklarna var randomiserade kontrollerade studier (RCT) och fyra var studier av annan design. Sammanfattningsvis visade resultaten i studierna att familjeterapi eller familjebaserade interventioner ledde till minskning av depressionssymtom, oftast med likvärdig effekt som annan behandling, i de fall där det gavs, och ibland med bättre effekt. Resultat i form av positiva bieffekter på komorbida symptom samt på familj och andra omgivande faktorer kunde också visas i några av studierna. Resultaten behöver dock tolkas med stor försiktighet med tanke på några av studiernas skiftande och måttliga kvalitet. Liknande resultat stöds av vissa metaanalyser men ifrågasätts i andra. Slutsatsen av denna litteraturstudie var att det finns evidens för att kunna rekommendera valet av familjeterapi som behandling vid depression av barn och ungdomar när EBP (Evidensbaserad praktik) får utgöra grundvalen och när de tre effektmåtten efficacy, effectiveness och efficiency tas i beaktande. Det behövs fler högkvalitativa studier på familjeterapi med avstamp i EBP och med fler utfallsmått än symtomeffekt på den primära diagnosen. Att manualisera familjeterapimetoder eller konceptualisera s.k. common factors skulle kunna vara ett viktigt steg mot att kunna identifiera och generalisera specifika förändringsmekanismer.

Vaccination is a great achievement of current health that every year saves millions of lives, these strengthen and help the body’s immune system to prevent diseases or reduce its mortality. Immunization is an essential part of primary health care as a primary element for the prevention and control of infectious diseases, thus helping to safeguard global and national health security. (WHO, 2023). It is a quantitative study, with an experimental design, descriptive cross-sectional, with a sample of 37 children (as) who come with their guardian to the CESSA Macuspana for vaccination. The results show that 20 (54.05%) have a good level of compliance, while 17 (45.95%) do not have a complete vaccination schedule; that is, it is concluded that it is necessary to work on missed vaccination opportunities to increase the complete schemes in children of Macuspana., La vacunación es un gran logro de la salud actual que cada año salva millones de vidas, estas refuerzan y ayudan al sistema inmune del cuerpo para evitar enfermedades o disminuir su mortalidad. La inmunización forma parte esencial de la atención primaria a la salud siendo un elemento primordial para la prevención y el control de las enfermedades infecciosas ayudando así a resguardar la seguridad sanitaria mundial y nacional. (OMS, 2023). Es un estudio cuantitativo, con diseño no experimental, descriptivo de corte transversal, con una muestra de 37 niños (as) que acuden con su tutor al CESSA Macuspana para vacunación. Los resultados muestran que 20 (54.05%) tienen buen nivel de cumplimiento, mientras que 17 (45.95%) no tienen un esquema de vacunación completo; es decir, se concluye que es necesario trabajar en las oportunidades perdidas de vacunación para aumentar los esquemas completos en niños de Macuspana.

This scientific article focuses on a detailed analysis of the crime of sexual violation of children and young people, as typified in article 308a of the Bolivian Penal Code. The main objective is to deepen the understanding of the nature and nature of this crime, emphasizing the importance of protecting the rights and safety of children under 14 years of age, as they are particularly vulnerable to this type of abuse. In this sense, the legal rights protected by said provisions will be interpreted from a legal point of view, highlighting the importance of the fundamental principle of the physical, mental and gender inviolability of minors. Likewise, the legal nature of the crime in the context of criminal law and its role in protecting the human rights of children and young people will be examined in detail. Special emphasis will be placed on the legal and social consequences of the commission of this crime. From a legal perspective, the sanctions and safeguards provided for by Bolivian legislation will be analyzed, as well as their effectiveness in preventing and prosecuting such crimes. In terms of social impact, the devastating social impact of the rape of babies, girls, boys and young people will be explored, taking into account factors such as revictimization, access to justice and the need for comprehensive care for victims. The purpose of this article is to provide a deep and rigorous analysis of the crime of sexual violation of babies, girls, boys and young people in order to promote the understanding of its essential and legal nature, as well as its legal and social implications in the context of Bolivian laws., Este artículo científico se centra en un análisis detallado del delito de violación sexual de niños, niñas, niños y jóvenes, según tipificado en el artículo 308a del Código Penal boliviano. El objetivo principal es profundizar en la comprensión de la naturaleza y naturaleza de este delito, enfatizando la importancia de proteger los derechos y la seguridad de los niños menores de 14 años, ya que son particularmente vulnerables a este tipo de abuso. En este sentido, los bienes jurídicos protegidos por dichas disposiciones serán interpretados desde el punto de vista jurídico, destacando la importancia del principio fundamental de la inviolabilidad física, psíquica y de género de los menores. Asimismo, se examinará en detalle la naturaleza jurídica del delito en el contexto del derecho penal y su función de protección de los derechos humanos de niños y jóvenes. Se hará especial énfasis en las consecuencias jurídicas y sociales de la comisión de este delito. Desde una perspectiva jurídica, se analizarán las sanciones y salvaguardas previstas por la legislación boliviana, así como su efectividad para prevenir y perseguir tales delitos. En términos de impacto social, se explorará el devastador impacto social de la violación de bebés, niñas, niños y jóvenes, teniendo en cuenta factores como la revictimización, el acceso a la justicia y la necesidad de una atención integral a las víctimas. El propósito de este artículo es proporcionar un análisis profundo y riguroso del delito de violación sexual de bebés, niñas, niños y jóvenes con el fin de promover la comprensión de su naturaleza esencial y jurídica, así como de sus implicaciones jurídicas y sociales en el contexto de las leyes bolivianas.

The main objective of this research was to analyze the cultural patterns generated by the family in relation to child labor, given its significant impact on the formation of individual perceptions and the configuration of mental, social and cultural constructs that influence the interaction of people in society. To achieve this objective, a mixed approach methodology was used that made it possible to process both qualitative and quantitative data, through the inductive method, as well as the application of the survey technique. The results obtained in this research shed light on the normalization of child labor in family contexts and among individuals from vulnerable environments, characterized by needs and deficiencies. These findings indicate the urgency of an effective and rapid response by the State, the judicial system and its operators, government authorities and society as a whole. This response must be focused on education and the promotion of preventive programs and the eradication of child labor, with the aim of safeguarding the rights of children and adolescents. In conclusion, this research highlights the prevailing need to address the problem of child labor from a multidisciplinary approach that involves various social actors, in order to guarantee an adequate environment for the development and well-being of children and young people., La presente investigación tuvo como objetivo principal analizar los patrones culturales generados por la familia en relación con el trabajo infantil, dado su significativo impacto en la formación de las percepciones individuales y en la configuración de constructos mentales, sociales y culturales que influyen en la interacción de las personas en la sociedad. Para lograr este objetivo, se empleó una metodología de enfoque mixto que posibilitó el procesamiento de datos tanto cualitativos como cuantitativos, a través del método inductivo, así como la aplicación de la técnica de encuesta. Los resultados obtenidos en esta investigación arrojaron luz sobre la normalización del trabajo infantil en contextos familiares y entre individuos de entornos vulnerables, caracterizados por necesidades y carencias. Estos hallazgos indican la urgencia de una respuesta eficaz y rápida por parte del Estado, el sistema judicial y sus operadores, las autoridades gubernamentales y la sociedad en su conjunto. Esta respuesta debe estar enfocada en la educación y la promoción de programas preventivos y de erradicación del trabajo infantil, con el objetivo de salvaguardar los derechos de los niños, niñas y adolescentes. En conclusión, esta investigación subraya la necesidad imperante de abordar el problema del trabajo infantil desde un enfoque multidisciplinario que involucre a diversos actores sociales, con el fin de garantizar un entorno adecuado para el desarrollo y bienestar de los niños y jóvenes.

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study. APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, p

Objective: To identify the impacts of the COVID-19 pandemic on the health care of children and youth with oncological diseases. Method: Scoping review based on the Joanna Briggs Institute (JBI) methodological framework. To describe the research question, the population, concept, and context (PCC) strategy was used. The searches occurred in September 2022 in the BVS, Cinahl, Scopus, Lilacs, and PubMed databases, with the following descriptors: cancer; children; teenagers; pandemic; Covid; oncology; child; adolescent; and neoplasia. Rayyan software was used to select the studies, following the PRISMA recommendations. The content analysis method proposed by Bardin was used. Result: There were several impacts of the pandemic on care for children and adolescents’ oncology, related to daily life, the need to (re) organize health services, and, in this context, barriers were identified in maintaining treatment, postponing/reducing the offer of care, which impacted the reduction of specialized professionals and the supply of surgeries, and reduction of inputs and medicines. In the emotional sphere, the impacts were related to the intensification of feelings of fear and anxiety. Conclusion: In addition to the impacts caused by the pandemic, the need for awareness raising and support work for children and their families by primary care and specialized care teams became evident when they could not be assisted by other services, in addition to continued care at home., Objetivo: Identificar os impactos da pandemia de Covid-19 no cuidado à saúde da população infantojuvenil com doença oncológica. Método: Revisão de escopo, com base no referencial metodológico do Joanna Briggs Institute (JBI). Para a formulação da questão de pesquisa, foi utilizada a estratégia Population, Concept e Context (PCC). As buscas ocorreram em setembro de 2022, nas bases de dados BVS, Cinahl, Scopus, Lilacs e Pubmed, com os descritores: câncer; children; adolescents; pandemia; Covid; oncologia; criança; adolescente; e neoplasia. O software Rayyan foi utilizado para a seleção dos estudos, seguindo as recomendações do PRISMA. Para a análise, utilizou-se o método de Análise de Conteúdo proposto por Bardin. Resultado: Constatou-se diversos impactos da pandemia nos atendimentos ao público oncológico infantojuvenil, relacionados ao cotidiano, a necessidade de (re)organização dos serviços de saúde e, nesse contexto, identificaram-se barreiras na manutenção do tratamento, adiamento/redução da oferta de atendimentos, que impactou na redução de profissionais especializados e na oferta de cirurgias, redução de insumos e medicamentos. No âmbito emocional, os impactos foram relacionados a intensificação dos sentimentos de medo e ansiedade. Conclusão: Além dos impactos causados pela pandemia, ficou evidente a necessidade de sensibilização e de um trabalho de suporte às crianças e suas famílias pelas equipes de atenção primária e atenção especializada, quando essas não podem ser assistidas por outros serviços, além de um cuidado continuado no domicílio.

Dengue is a viral infection which is transmitted by the Aedes aegypti mosquito and has four serotypes (DENV-1 to DENV-4). The disease triggers a variety of clinical manifestations, ranging from mild forms without warning signs to severe lifethreatening forms. We present the case of a 5-year-old boy, from the province of Callao, whose first symptoms were fever, headache and general malaise. On the third day, the child had mild abdominal pain and little vomiting; subsequently, abdominal distension, jaundice and choluria. He was admitted to the pediatric intensive care unit being alert and with moderate dehydration, jaundice, edema, distended and tender abdomen, shifting dullness and liver 2 cm below the right costal margin. Complementary tests revealed liver failure, hepatosplenomegaly and pleural effusion in the bases. Using a reactive IgM ELISA, severe dengue was diagnosed, as well as a superinfection due to probable spontaneous bacterial peritonitis. He started treatment with antibiotics, furosemide, fresh frozen plasma, cryoprecipitate and metamizole. As the child did not get better, the diuretic was optimized, and human albumin was administered. Thereafter, he got better showing decreased ascites, edema, jaundice and pleural effusion; improvement of the liver and coagulation profile; and being afebrile. He unexpectedly presented respiratory distress due to congestive heart failure caused by dilated cardiomyopathy diagnosed by echocardiography; thus, he was treated with diuretics. The patient was discharged afebrile, without edema and with resolution of liver failure and coagulation disorder., El dengue es una infección viral transmitida a través del mosquito Aedes aegypti y presenta cuatro serotipos (DENV-1 a DENV-4). La enfermedad desencadena una variedad de manifestaciones clínicas, desde formas leves sin signos de alarma hasta formas graves, potencialmente mortales. Se presenta el caso de un niño de cinco años, procedente de la provincia del Callao, cuyos síntomas iniciales fueron fiebre, cefalea y malestar general. Al tercer día, el niño manifiestó dolor abdominal leve y vómitos escasos; posteriormente, distensión abdominal, ictericia y coluria. Fue hospitalizado en la unidad de cuidados intensivos pediátricos con deshidratación moderada, ictericia, edemas, abdomen distendido y doloroso, matidez desplazable, hígado a 2 cm debajo del reborde costal derecho y lúcido. Por exámenes complementarios, se evidenció falla hepática, hepatoesplenomegalia y derrame pleural en bases. Se diagnosticó dengue grave a través de una prueba de ELISA Ig M reactivo más sobreinfección por probable peritonitis bacteriana espontánea. Se inició el tratamiento con antibióticos, furosemida, plasma fresco congelado, crioprecipitado y metamizol. Al no observarse mejoría, se optimizó el diurético y se administró albúmina humana. Mostró mejoría con disminución de ascitis, edemas, ictericia y efusión pleural; también mejora del perfil hepático y de la coagulación, además de encontrarse afebril. Presentó inesperadamente dificultad respiratoria por insuficiencia cardiaca congestiva debido a miocardiopatía dilatada según ecocardiografía; se manejó con diuréticos. Fue dado de alta en estado afebril, sin edemas y con resolución de falla hepática y trastorno de coagulación.

Mental health is one of the current pillars of global health; therefore, it is considered an essential factor in the wellbeing and quality of human life. The dramatic growth in the incidence and prevalence of mental disorders has brought about a burden of silent and unsustainable disease for healthcare systems, especially in younger age groups such as children and adolescents. Although major depressive disorder, anxious syndrome, and conduct and eating disorders are some of the most frequent in this age group, attention-deficit hyperactivity disorder (ADHD) is also an entity of interest affecting between 5% and 10% of children. There exists a pharmacological treatment for this condition, and it is based on stimulant and nonstimulant medications. Evidence of the highest quality has recently demonstrated that children and adolescents who were administered ADHD medications had a higher risk of some cardiovascular event compared to those who were not. Considering the impact and relevance of ADHD in the child and adolescent populations at present, as well as the use of drugs for its control, it is imperative to have evidence of the highest quality for decision-making in clinical practice. To date, there is no evidence in Spanish that has synthesized and analyzed this phenomenon. Based on the foregoing, the objective of this review is to analyze the most recent evidence of the association between cardiovascular risk and pharmacotherapy in pediatric patients with ADHD. A literature search was conducted using the search terms "Cardiovascular Risk," "Attention Deficit Hyperactivity Disorder," and "Pediatrics," in addition to synonyms, which were combined with the operators "AND" and "OR," in the PubMed, ScienceDirect, Web of Science, and MEDLINE databases. After reviewing the most recent literature, it was identified that the quality of the current evidence regarding the association between increased cardiovascular risk secondary to pharmacotherapy in children and adolescent, La salud mental constituye uno de los pilares actuales de la salud global, por tanto, se considera un factor esencial en el bienestar y calidad de vida del ser humano. El crecimiento dramático de la incidencia y prevalencia de trastornos mentales ha acarreado una carga de enfermedad silenciosa e insostenible para los sistemas de salud, sobre todo en grupos etarios más precoces, como niños y adolescentes. Aunque los desórdenes depresivos mayores, síndromes ansiosos y desorden de la conducta y la alimentación son algunos de los más frecuentes en esta edad, el trastorno por déficit de atención con hiperactividad (TDAH) también es una entidad de interés que afecta entre el 5 %-10 % de los niños. Para su manejo, existe tratamiento farmacológico basado en medicamentos estimulantes y no estimulantes. Recientemente, evidencia de la más alta calidad demostró que existe mayor riesgo de que niños y adolescentes sufran algún evento cardiovascular por la administración de fármacos para el TDAH, en comparación con aquellos que no recibieron la medicación. Considerando el impacto y la pertinencia del TDAH en las poblaciones infantil y adolescente en la actualidad, así como el uso de fármacos para su control, es imperativo disponer de evidencia de la mejor calidad para la toma de decisiones en la práctica asistencial. A la fecha, no existe evidencia en habla hispana que haya sintetizado y analizado este fenómeno. Con base en lo anterior, el objetivo de esta revisión consiste en analizar la evidencia más reciente sobre la asociación entre riesgo cardiovascular y farmacoterapia en pediátricos por el TDAH. Se realizó una búsqueda bibliográfica utilizando los términos de búsqueda “Riesgo Cardiovascular”, “Déficit de Atención por Hiperactividad” y “Pediátricos”, además de sinónimos, los cuales fueron combinados con los operadores “AND” y “OR”, en las bases de datos PubMed, ScienceDirect, Web of Science y MEDLINE. Luego de revisarse la literatura más reciente, se identificó que, aunque l

Objective. To measure the level of competency development of Peruvian primary care nurses in the control of growth and development of children under five years old. Methods. A cross-sectional, descriptive, quantitative study was designed with a population group of 100 nurses working in primary care health networks located in Lima, Ica, and Trujillo, using a non-probabilistic census sampling method. Data were collected using observation as the technique; the instrument was a performance checklist for growth, development, and immunizations. Results. The majority of the studied nurses presented a low level of competencies related to the growth and development of Peruvian children under five years old (60%), while 37% presented a medium level of performance in these competencies, and only 3% demonstrated a high level. Conclusions. Peruvian primary care pediatric nurses present low levels of competencies in the control of growth and development in children., Objetivo. Medir el nivel de desarrollo de competencias de las enfermeras y los enfermeros peruanos de atención primaria en el control del crecimiento y desarrollo (CRED) de niñas y niños menores de cinco años. Métodos. Se diseñó un estudio transversal, descriptivo, cuantitativo, con un grupo poblacional de 100 enfermeras y enfermeros que trabajan en las redes de salud de atención primaria ubicados en Lima, Ica y Trujillo, con una muestra no probabilística de carácter censal. Para recabar datos se utilizó la observación como técnica; el instrumento fue una lista de chequeo para desempeño: crecimiento, desarrollo e inmunizaciones. Resultados. La mayoría de las profesionales enfermeras estudiadas presentaban un nivel bajo en las competencias relacionadas con el crecimiento y desarrollo de niños y niñas peruanos menores de cinco años (60 %), mientras que el 37 % presentaba un nivel medio en el desempeño de estas competencias y sólo en el 3 % se pudo objetivar un nivel alto. Conclusiones. Las enfermeras y los enfermeros pediátricos peruanos de atención primaria presentan bajos niveles de competencias en el control de crecimiento y desarrollo en niños.

Background: The normal nasolabial structure of infants and chil-dren from East Asian, specifically Indonesian, descent groups has been less explored in the literature. This anthropometric study is used as a guide in lip repair in patients with clefts. This retrospective study used archived CT images from the Indonesian population. Materials and Methods: Computed tomography records of children under 5 years of age were extracted from a provincial hospital. The images were then filtered based on the inclusion and exclusion criteria and then the 2D slices were reconstructed using the open source software Invesalius. Twenty-five variable nasolabial parameters of the nasolabial structure were then measured in the 3D rendering mode. Images with craniofacial dysmorphism or cannulas that passed over the nasolabial structure were excluded. Results were summarized using descriptive statistics. Results: Fourteen of 128 CT images were included in this study. The samples were divided into two age groups: 0-12 months and 25-54 months. There were moderate to strong, positive correlations between age and all nasolabial variables, which were statistically significant (p<0.05) except for nasal length, nares circumference, columella width, superior philtrum width, philtrum column height, and cutaneous upper lip height. Conclusions: This study described anthropometric measurements of normal nasolabial structures as a reference point for lip correction surgery. However, to obtain more accurate anthropometric guidelines, further studies with larger sample sizes are desirable. Although surgical repair of the lip is usually performed within the first year of life, some cases of surgery are performed after infancy., Antecedentes: La estructura naso labial normal de bebés y niños de grupos de ascendencia de Asia oriental, específicamente de Indonesia, ha sido menos explorada en la literatura. Este estudio antropométrico se utiliza como guía en la reparación del labio en pacientes con fisuras. Este estudio retrospectivo utilizó imágenes de tomografía computarizada archivadas de la población indonesia. Materiales y Métodos: Se extrajeron los registros de tomografía computarizada de niños menores de 5 años de un hospital provincial. Luego, las imágenes se filtraron según los criterios de inclusión y exclusión y luego se reconstruyeron los cortes 2D utilizando el software de código abierto Invesalius. Luego se midieron veinticinco parámetros nasolabiales variables de la estructura nasolabial en el modo renderizado 3D. Se excluyeron imágenes con dismórfica craneofacial y cánula que pasa sobre la estructura nasolabial. Los resultados se resumen mediante estadística descriptiva. Resultado: En este estudio se incluyeron catorce de 128 imágenes de TC. Las muestras se dividieron en dos grupos de edad: 0-12 meses y 25-54 meses. Hubo una correlación positiva de moderada a fuerte entre la edad y todas las variables nasolabiales, que fueron estadísticamente significativas (p<0,05) excepto la longitud nasal, la circunferencia de las narinas, el ancho de la columela, el ancho del filtrum superior, la altura de la columna del filtrum y la altura cutánea del labio superior. Conclusión: Este estudio describió las medidas antropométricas de estructuras nasolabiales normales como base para la cirugía de corrección de labios. Sin embargo, para obtener directrices antropométricas más precisas, son deseables más estudios con tamaños de muestra más grandes. Aunque la reparación quirúrgica del labio normalmente se realiza dentro del primer año de vida, en algunos casos la cirugía se realiza después de la infancia.

Introduction: Pediatric liquid medications (PLM) are frequently administered to children, yet their usage may contribute to the onset of dental caries. Despite its prevalence, there is a notable scarcity of scientific research regarding caregivers’ knowledge of this potential cariogenic risk. Objective: This study aims to assess the knowledge of the main caregivers of children aged 5 to 12 years concerning the cariogenic potential associated with the use of PLM. Materials and Methods: A cross-sectional analytical obser-vational study involving 152 primary caregivers of children aged 5 to 12 was conducted. Data were collected on caregivers’ perceptions of the cariogenic risk associated with PLMs and their consumption habits. The study also assessed oral hygiene routines and evaluated the level of information provided by healthcare professionals. Results: Research findings indicated a significant lack of awa-reness among primary caregivers regarding the cariogenic risks of PLMs, with 78.95% being unaware of these risks and 47.37% unaware of the sugars present in such medications. Additionally, a high rate of PLM consumption was observed, with 63% of caregivers using them in the last year. The study underscored a notable absence of guidance from healthcare professionals, as 91.45% of the caregivers stated that they had not received instructions on tooth brushing after the administration of the PLM. Conclusions: The study highlights a significant lack of awa-reness among primary caregivers regarding the cariogenic risks associated with the ingestion of pediatric liquid medications. This deficit in information and preventive measures presents a substantial obstacle to children’s oral health. To address this issue, it is crucial for healthcare professionals to offer comprehensive guidance and promote preventive measures., Introducción: La administración de medicamentos líquidos pediátricos (MLP) es una práctica común en la población infantil y puede estar vinculada al desarrollo de lesiones de caries dental. Sin embargo, la evidencia científica que aborda el conocimiento de los cuidadores acerca de este riesgo cariogénico es escasa. Objetivo: Este estudio busca determinar el conocimiento de los cuidadores principales de niños de 5 a 12 años sobre el potencial cariogénico asociado al consumo de MLP. Materiales y Métodos: Se llevó a cabo un estudio observacional analítico transversal que incluyó a 152 cuidadores principales de niños en el rango de edad de 5 a 12 años. Se recopiló información sobre la percepción de los cuidadores acerca del riesgo cariogénico de los MLP, así como sobre sus patrones de consumo. Además, se registraron las prácticas de higiene oral y se evaluó el nivel de información proporcionado por los profesionales de la salud. Resultado: Los hallazgos de la investigación revelaron que un 78,95% de los cuidadores principales desconocen el riesgo cariogénico asociado al consumo de medicamentos líquidos pediátricos (MLP), y un 47,37% de ellos no eran conscientes de la presencia de azúcares en dichos medicamentos. Además, se observó un elevado índice de consumo de MLP, con un 63% de los cuidadores que los utilizaron en el último año. Se destacó la falta de orientaciones por parte de los profesionales de la salud, ya que, un 91,45% de los tutores afirmaron no haber recibido instrucciones sobre el cepillado dental posterior a la administración de los MLP. Conclusión: Este estudio evidencia un relevante porcentaje de desconocimiento entre los cuidadores principales acerca del riesgo cariogénico asociado a la ingesta de medicamentos líquidos pediátricos. La falta de información y medidas preventivas constituye un desafío significativo para la salud oral de los niños. Es imperativo que los profesionales de la salud proporcionen información detallada y fomenten prácticas de pre

Introduction: Early childhood caries is still very prevalent, mainly in developing countries, and it is related to the quality of life of children due to early tooth loss. Objective: The study objective was to determine the association between dental caries and its clinical consequences on nutritional status in children of the “Vaso de Leche (Glass of Milk)’’ social program, in Puno City, Peru, during the year 2020. Materials and Methods: An observational, descriptive-correlational, cross-sectional study; the sample consisted of 740 children between 1 and 5 years old who met the selection criteria; the clinical consequences of untreated dental caries were evaluated using the PUFA index and the prevalence of caries with def-t; the nutritional status was determined by the weight and height of the child according to protocols (NTS No. 357 - MINSA /2017/ DGIESP); the data were analyzed with the SPSS-v25 program, the association between variables was evaluated with the chi-square test, Mann-Whitney U test and Spearman’s Rho test, considering significance at a p-value <0.05. Results: No significant relationship was found when dental caries was evaluated with the nutritional condition (p<0.05). However, when the def-t index values were related to the nutritional condition of the children, a significant difference was found (p<0.05). There was no significant difference with the PUFA index (p>0.05). Conclusions: There is no association between early childhood caries and nutritional status in children aged between 3 and 5 years; however, a significant relationship was found between the values of the def-t index and the nutritional status of the children., Introducción: La caries infantil temprana sigue siendo muy prevalente, principalmente en los países en desarrollo, y está relacionada con la calidad de vida de los niños debido a la pérdida temprana de dientes. Objetivo: El objetivo del estudio fue determinar la asociación entre la caries dental y sus consecuencias clínicas sobre el estado nutricional en niños del programa social “Vaso de Leche”, en la ciudad de Puno, Perú, durante el año 2020. Materiales y Métodos: Estudio observacional, estudio descriptivo-correlacional, transversal; la muestra estuvo conformada por 740 niños entre 1 y 5 años que cumplieron con los criterios de selección, se evaluaron las consecuencias clínicas de la caries dental no tratada mediante el índice PUFA y la prevalencia de caries con d-t; el estado nutricional se determinó mediante el peso y talla del niño según protocolos (NTS N°357 - MINSA/2017/DGIESP; los datos se analizaron con el programa SPSS-v25, la asociación entre variables se evaluó con el chi); -cuadrado, U de Mann-Whitney y Rho de Spearman, considerando significancia a un valor de p<0,05. Resultado: No se encontró relación significativa cuando se evaluó la caries dental con la condición nutricional (p<0,05). Sin embargo, cuando los valores del índice d-t se relacionaron con la condición nutricional de los niños, se encontró una diferencia significativa (p<0,05). No hubo diferencia significativa con el índice PUFA (p>0,05). Conclusión: No existe asociación entre caries de la primera infancia y el estado nutricional en niños de 3 a 5 años; sin embargo, se encontró una relación significativa entre los valores del índice d-t y el estado nutricional de los niños.

Self-injury is the act by which a person intentionally causes death. The aim of this research was to determine the frequency of attempted self-injury and the associated risk factors in 35 patients aged 7 to 13 years who were admitted to the Emergency Department of the Servicio Desconcentrado Hospital Universitario Pediatrico Dr. Agustin Zubillaga during the period January 2017 to June 2022. 63% of the patients were female and 91% of them were older than 10 years old. Eighty-three percent of the patients had no pathological medical history, 97% had no psychiatric pathology and 86% of the cases showed no history of medication use. In 83% of the cases there was no family history of suicide. In the Graffar scale it was found that 61% of the cases were located in stratum IV. Ninety-one percent of the patients were studying and 77% of them were in high school. In 42% of the cases the family group consisted of 4 members. Thirty-nine percent of the patients lived with their mother and siblings and 30% with their father and siblings. Regarding the filial relationship, most of them had no relationship with their parents (33%) and 19% had a bad relationship. In 78% of the cases, some type of substance was ingested orally as a method of self-injury. In 94% of the cases, the attempt at self-injury occurred at home and was unsuccessful. Sixty-seven percent had not attempted it before and 61% had no warning beforehand. The main reasons for attempted self-harm were fights with relatives (51%) and arguments with the mother (17%)., La autólisis es el acto por el que una persona se provoca la muerte de forma intencionada. El presente trabajo de investigación tuvo como objetivo determinar la frecuencia de intento de autólisis y los factores de riesgo asociados en 35 pacientes de 7 a 13 años que ingresaron a la Emergencia del Servicio Desconcentrado Hospital Universitario Pediátrico Dr. Agustín Zubillaga durante el periodo enero 2017 a junio 2022. 63% de los pacientes fueron del sexo femenino y 91% de ellos eran mayores de 10 años. El 83% de los pacientes no tenían antecedentes médicos patológicos, 97% no presentaban patología psiquiátrica y 86% de los casos no mostraban historial de consumo de medicamentos. En el 83% de los casos no había antecedentes familiares de suicidio. En la escala de Graffar se encontró que el 61% de los casos se ubicó en el estrato IV. El 91% de los pacientes estudiaba siendo que 77% de ellos cursaba nivel secundaria. En 42% de los casos el grupo familiar estuvo formado por 4 integrantes. El 39% de los pacientes convivía con su madre y hermanos y el 30% con su padre y hermanos. Con respecto a la relación filial, la mayoría no tienen relación alguna con los padres (33%) y el 19% mantenía mala relación. En el 78% de los casos se ingirió algún tipo de sustancia por vía oral como método de autólisis. En el 94% de los casos, el intento de autólisis ocurrió en casa y fue fallido. El 67% no lo había intentado con anterioridad y el 61% no lo advirtió con anticipación. Los motivos principales de intento de autólisis fueron peleas con familiares (51%) y discusión con la madre (17%).

Following the authorization the use of COVID-19 vaccines in babies age six months through children four years old in the United States, some individuals (parents, pediatricians, and communicators) framed COVID-19 vaccination as an issue of access, while many others expressed hesitancy and some resisted recommendations from the US Centers for Disease Control and Prevention. In this context, this study aimed to explore: 1) divergent reactions to the authorization of COVID-19 vaccine use in children aged six months to four years; and 2) opposing logics underlying attitudes towards pro-vaccination, anti-vaccination, and vaccine hesitancy regarding COVID-19 vaccines. To achieve this, a digital ethnography was conducted, involving monitoring of 5,700 reactions to a series of eight infographics published on social media by the John Hopkins Bloomberg School of Public Health, and participant observation in an online focus group over a one-year period, from December 2021 to December 2022, consisting of 18 mothers. The findings suggest that healthcare professionals should consider different notions of “risk” when interacting with patients, especially those who are hesitant to vaccinate., Luego de que se autorizara en EEUU el uso de la vacuna contra el covid-19 en bebés de seis meses a niños y niñas de cuatro años, algunas personas (padres, madres, pediatras y comunicadores) plantearon la vacunación contra el covid-19 como una cuestión de acceso; sin embargo, muchas otras se mostraron reacias y otras se resistieron a las recomendaciones de los Centers for Disease Control and Prevention de EEUU. En este contexto, este estudio se propuso explorar: 1) reacciones divergentes ante la autorización de uso de la vacuna contra el covid-19 en niños y niñas de seis meses a cuatro años; y 2) lógicas contrapuestas que subyacen a las actitudes provacunación, antivacunación y vacilación ante las vacunas contra el covid-19. Para ello, se realizó una etnografía digital, con monitoreo de 5.700 reacciones a una serie de ocho infografías publicadas en las redes sociales por la John Hopkins Bloomberg School of Public Health, y observación participante en un grupo focal en línea a lo largo de un año, desde diciembre de 2021 hasta diciembre de 2022, conformado por 18 madres. Los resultados indican que el personal médico debe considerar diferentes nociones de “riesgo” al interactuar con los pacientes, especialmente aquellos que dudan en vacunarse.

Statin therapy is a cornerstone in the treatment of systemic vascular diseases. However, statins have failed to translate as therapeutics for pulmonary vascular disease. Early pulmonary vascular disease in the setting of congenital heart disease (CHD) is characterized by endothelial dysfunction, which precedes the more advanced stages of vascular remodeling. These features make CHD an ideal cohort in which to re-evaluate the potential pulmonary vascular benefits of statins, with a focus on endothelial biology. However, it is critical that the full gamut of the pleiotropic effects of statins in the endothelium are uncovered. The purpose of this investigation was to evaluate the therapeutic potential of simvastatin for children with CHD and pulmonary over-circulation, and examine mechanisms of simvastatin action on the endothelium. Our data demonstrate that daily simvastatin treatment preserves endothelial function in our shunt lamb model of pulmonary over-circulation. Further, using pulmonary arterial endothelial cells (PAECs) isolated from Shunt and control lambs, we identified a new mechanism of statin action mediated by increased expression of the endogenous Akt1 inhibitor, C-terminal modifying protein (CTMP). Increases in CTMP were able to decrease the Akt1-mediated mitochondrial redistribution of endothelial nitric oxide synthase (eNOS) which correlated with increased enzymatic coupling, identified by increases in NO generation and decreases in NOS-derived superoxide. Together our data identify a new mechanism by which simvastatin enhances NO signaling in the pulmonary endothelium and identify CTMP as a potential therapeutic target to prevent the endothelial dysfunction that occurs in children born with CHD resulting in pulmonary over-circulation.

OBJECTIVE: This study investigates how team cognition occurs in care transitions from operating room (OR) to intensive care unit (ICU). We then seek to understand how the sociotechnical system and team cognition are related. BACKGROUND: Effective handoffs are critical to ensuring patient safety and have been the subject of many improvement efforts. However, the types of team-level cognitive processing during handoffs have not been explored, nor is it clear how the sociotechnical system shapes team cognition. METHOD: We conducted this study in an academic, Level 1 trauma center in the Midwestern United States. Twenty-eight physicians (surgery, anesthesia, pediatric critical care) and nurses (OR, ICU) participated in semi-structured interviews. We performed qualitative content analysis and epistemic network analysis to understand the relationships between system factors, team cognition in handoffs and outcomes. RESULTS: Participants described three team cognition functions in handoffs-(1) information exchange, (2) assessment, and (3) planning and decision making; information exchange was mentioned most. Work system factors influenced team cognition. Inter-professional handoffs facilitated information exchange but included large teams with diverse backgrounds communicating, which can be inefficient. Intra-professional handoffs decreased team size and role diversity, which may simplify communication but increase information loss. Participants in inter-professional handoffs reflected on outcomes significantly more in relation to system factors and team cognition (p < 0.001), while participants in intra-professional handoffs discussed handoffs as a task. CONCLUSION: Handoffs include team cognition, which was influenced by work system design. Opportunities for handoff improvement include a flexibly standardized process and supportive tools/technologies. We recommend incorporating perspectives of the patient and family in future work.

Clinicians form initial impressions about a childs diagnosis based on behavioral features, but research has not yet identified specific behaviors to guide initial diagnostic impressions. Participants were toddlers (N = 55, mean age 22.9 months) from a multi-site early detection study, referred for concern for ASD due to screening or parent/provider concern. Within 5 min of meeting a child, clinicians noted ASD or non-ASD impression, confidence in impression, and behaviors that informed their impression. These clinicians also determined final diagnoses for each child. When a childs final diagnosis was ASD (n = 35), senior clinicians formed an initial impression of ASD in 22 cases (63%) but missed 13 cases (37%). When final diagnosis was non-ASD (n = 20), senior clinicians made an initial impression of non-ASD in all cases (100%). Results were similar among junior clinicians. Senior and junior clinicians used the same behaviors to form accurate impressions of ASD and non-ASD: social reciprocity, nonverbal communication, and eye contact. Senior clinicians additionally used focus of attention when forming accurate impressions of ASD and non-ASD; junior clinicians used this behavior only when forming accurate non-ASD impressions. Clinicians initial impressions of ASD are very likely to be consistent with final diagnoses, but initial impressions of non-ASD need follow-up. Toddlers who show all four atypical behaviors (social reciprocity, nonverbal communication, eye contact, and focus of attention) might receive expedited ASD diagnoses. However, presence of apparently typical behaviors should not rule out ASD; for some children a longer evaluation is necessary to allow for more opportunities to observe subtle social behavior.

Inequities in urban greenspace have been identified, though patterns by race and socioeconomic status vary across US settings. We estimated the magnitude of the relationship between a broad mixture of neighborhood-level factors and residential greenspace using weighted quantile sum (WQS) regression, and compared predictive models of greenspace using only neighborhood-level, only individual-level, or multi-level predictors. Greenspace measures included the Normalized Difference Vegetation Index (NDVI), tree canopy, and proximity of the nearest park, for residential locations in Shelby County, Tennessee of children in the CANDLE cohort. Neighborhood measures include socioeconomic and education resources, as well as racial composition and racial residential segregation. In this sample of 1012 mother-child dyads, neighborhood factors were associated with higher NDVI and tree canopy (0.021 unit higher NDVI [95% CI: 0.014, 0.028] per quintile increase in WQS index); homeownership rate, proximity of and enrollment at early childhood education centers, and racial composition, were highly weighted in the WQS index. In models constrained in the opposite direction (0.028 unit lower NDVI [95% CI: - 0.036, - 0.020]), high school graduation rate and teacher experience were highly weighted. In prediction models, adding individual-level predictors to the suite of neighborhood characteristics did not meaningfully improve prediction accuracy for greenspace measures. Our findings highlight disparities in greenspace for families by neighborhood socioeconomic and early education factors, and by race, suggesting several neighborhood indicators for consideration both as potential confounders in studies of greenspace and pediatric health as well as in the development of policies and programs to improve equity in greenspace access.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

BACKGROUND AND OBJECTIVES: Vamorolone is a dissociative agonist of the glucocorticoid receptor that has shown similar efficacy and reduced safety concerns in comparison with prednisone in Duchenne muscular dystrophy (DMD). This study was conducted to determine the efficacy and safety of vamorolone over 48 weeks and to study crossover participants (prednisone to vamorolone; placebo to vamorolone). METHODS: A randomized, double-blind, placebo-controlled and prednisone-controlled clinical trial of 2 doses of vamorolone was conducted in participants with DMD, in the ages from 4 years to younger than 7 years at baseline. The interventions were 2 mg/kg/d of vamorolone and 6 mg/kg/d of vamorolone for 48 weeks (period 1: 24 weeks + period 2: 24 weeks) and 0.75 mg/kg/d of prednisone and placebo for the first 24 weeks (before crossover). Efficacy was evaluated through gross motor outcomes and safety through adverse events, growth velocity, body mass index (BMI), and bone turnover biomarkers. This analysis focused on period 2. RESULTS: A total of 121 participants with DMD were randomized. Vamorolone at a dose of 6 mg/kg/d showed maintenance of improvement for all motor outcomes to week 48 (e.g., for primary outcome, time to stand from supine [TTSTAND] velocity, week 24 least squares mean [LSM] [SE] 0.052 [0.0130] rises/s vs week 48 LSM [SE] 0.0446 [0.0138]). After 48 weeks, vamorolone at a dose of 2 mg/kg/d showed similar improvements as 6 mg/kg/d for North Star Ambulatory Assessment (NSAA) (vamorolone 6 mg/kg/d-vamorolone 2 mg/kg/d LSM [SE] 0.49 [1.14]; 95% CI -1.80 to 2.78, p = 0.67), but less improvement for other motor outcomes. The placebo to vamorolone 6 mg/kg/d group showed rapid improvements after 20 weeks of treatment approaching benefit seen with 48-week 6 mg/kg/d of vamorolone treatment for TTSTAND, time to run/walk 10 m, and NSAA. There was significant improvement in linear growth after crossover in the prednisone to vamorolone 6 mg/kg/d group, and rapid reversal o

ObjectiveWe aimed to describe pediatric program directors' perceptions of existing mentorship programs in pediatric residencies, to assess whether characteristics used for mentor-mentee assignments impact mentoring outcomes, and to identify barriers to success in mentorship programs.MethodsWith the support of the Association of Pediatric Program Directors (APPD) Research Task Force, we conducted a cross-sectional survey study of all associate pediatric program directors in the United States in March 2022.ResultsNearly half (82 of 197, 41.6%) of programs responded. Most (87.8%) report having a formal mentoring program. Half of programs (51.4%) do not provide training to residents on how to be a mentee, and only slightly more than half (62.5%) provide training to faculty mentors. Most programs (80.6%) do not provide protected time for faculty mentors. There were no meaningful associations with characteristics used for mentorship matches and perceived successful mentorship. Top barriers from the program leadership perspective included faculty and residents lacking time, residents lacking skills to be proactive mentees, and inadequate funding.ConclusionsWhile a majority of programs have formal mentorship programs, many do not provide training to mentors or mentees. Barriers to mentorship include a lack of funding and time. National organizations, such as APPD and the Accreditation Council for Graduate Medical Education, have an opportunity to provide guidance and support for protected time, funding, and training for mentors and mentees.

Background Diffuse midline glioma (DMG) is a devastating pediatric brain tumor unresponsive to hundreds of clinical trials. Approximately 80% of DMGs harbor H3K27M oncohistones, which reprogram the epigenome to increase the metabolic profile of the tumor cells. Methods We have previously shown preclinical efficacy of targeting both oxidative phosphorylation and glycolysis through treatment with ONC201, which activates the mitochondrial protease ClpP, and paxalisib, which inhibits PI3K/mTOR, respectively. Results ONC201 and paxalisib combination treatment aimed at inducing metabolic distress led to the design of the first DMG-specific platform trial PNOC022 (NCT05009992). Conclusions Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such that we offer direction on future clinical trials in DMG.

BACKGROUND: Plusoptix photoscreeners are capable of measuring refractive errors of children from 1 meter distance, without cyloplegia. We aimed to compare refractive data obtained from the newest version of Plusoptix (model 12) with cycloplegic autorefraction. METHODS: We examined 111 consecutive children aged 3-7 years first by Plusoptix A12C under manifest condition and subsequently for cycloplegic refraction by Topcon KR-1 tabletop autorefractometer. Sphere, spherical equivalent, cylinder and axis of astigmatism measured by the two methods were analyzed to determine correlation, agreement and differences. RESULTS: Binocular examination of 111 children aged 4.86±1.27 years revealed good agreement between refractive data obtained by Plusoptix and cycloautorefraction, according to Bland-Altman plots. Significant (p < 0.001) and strong correlation was found between all refractive measurements (Pearsons r value of 0.707 for sphere, 0.756 for pherical equivalent, and 0.863 for cylinder). Plusoptix mean sphere, spherical equivalent and cylinder were 1.22, 0.56, and -1.32 D, respectively. Corresponding values for cycloautorefraction were 1.63, 1.00, and -1.26 D. The difference between axis of cylinder measured by the two methods was < 10° in 144 eyes (64.9%). CONCLUSIONS: Considering the significant agreement and correlation between Plusoptix photoscreener and cycloplegic autorefraction, the need for cycloplegic drops in refractive examination of children may be obviated. The mean difference between cylinder measurements are considerably trivial (0.06 D), but sphere is approximately 0.4 D underestimated by Plusoptix compared to cycloautorefraction, on average.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obt

We examined associations between prenatal fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) exposures and child respiratory outcomes through age 8-9 years in 1279 ECHO-PATHWAYS Consortium mother-child dyads. We averaged spatiotemporally modeled air pollutant exposures during four fetal lung development phases: pseudoglandular (5-16 weeks), canalicular (16-24 weeks), saccular (24-36 weeks), and alveolar (36+ weeks). We estimated adjusted relative risks (RR) for current asthma at age 8-9 and asthma with recent exacerbation or atopic disease, and odds ratios (OR) for wheezing trajectories using modified Poisson and multinomial logistic regression, respectively. Effect modification by child sex, maternal asthma, and prenatal environmental tobacco smoke was explored. Across all outcomes, 95% confidence intervals (CI) included the null for all estimates of associations between prenatal air pollution exposures and respiratory outcomes. Pseudoglandular PM2.5 exposure modestly increased risk of current asthma (RRadj = 1.15, 95% CI: 0.88-1.51); canalicular PM2.5 exposure modestly increased risk of asthma with recent exacerbation (RRadj = 1.26, 95% CI: 0.86-1.86) and persistent wheezing (ORadj = 1.28, 95% CI: 0.86-1.89). Similar findings were observed for O3, but not NO2, and associations were strengthened among mothers without asthma. While not statistically distinguishable from the null, trends in effect estimates suggest some adverse associations of early pregnancy air pollution exposures with child respiratory conditions, warranting confirmation in larger samples.

BACKGROUND: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery. METHODS: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders. RESULTS: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive

BACKGROUND: Health care providers are a key source of reports of infants to child welfare related to birthing peoples substance use. Many of these reports are overreports, or reports that exceed what is legally mandated, and reflect racial bias. We developed and evaluated a webinar for health professionals to address overreporting related to birthing peoples substance use. METHODS: This evaluation study collected data from health professionals registering to participate in a professional education webinar about pregnancy, substance use, and child welfare reporting. It collected baseline data upon webinar registration, immediate post-webinar data, and 6 month follow-up data. Differences in both pre-post-and 6 month follow-up data were used to examine changes from before to after the webinars in beliefs, attitudes, and practices related to pregnant and birthing people who use drugs and child welfare reporting. RESULTS: 592 nurses, social workers, physicians, public health professionals, and other health professionals completed the baseline survey. More than half of those completing the baseline survey (n = 307, 52%) completed one or both follow-up surveys. We observed statistically significant changes in five of the eleven opioid attitudes/beliefs and in four of the nine child welfare attitudes/beliefs from baseline to follow-ups, and few changes in control statements, i.e. beliefs we did not expect to change based on webinar participation. All of the changes were in the direction of less support for child welfare reporting. In particular, the proportion agreeing with the main evaluation outcome of I would rather err on the side of overreporting to child welfare than underreporting to child welfare decreased from 41% at baseline to 28% and 31% post-webinar and at 6-month follow up (p = 0.001). In addition, fewer participants endorsed reporting everyone at the 6 month follow-up than at baseline (12% to 22%) and more participants endorsed reporting no one at t

Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840). The prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. We find that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen, and that higher day 7 lumefantrine concentrations decrease the probability of ring-stage parasites in the early post-treatment period. Longitudinal amplicon sequencing reveals remarkably dynamic patterns of multiclonal infections that include new and persistent clones in both the early post-treatment and later time periods. Our data indicate that post-treatment parasite dynamics are highly complex despite efficacious therapy, findings that will inform strategies to optimize regimens in the face of emerging partial artemisinin resistance in Africa.

INTRODUCTION: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana. METHODS: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participants household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development. DISCUSSION: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa. TRIAL REGISTRATION: The trial was r

BACKGROUND: Global shortages of iodinated contrast media (ICM) during COVID-19 pandemic forced the imaging community to use ICM more strategically in CT exams. PURPOSE: The purpose of this work is to provide a quantitative framework for preserving iodine CNR while reducing ICM dosage by either lowering kV in single-energy CT (SECT) or using lower energy virtual monochromatic images (VMI) from dual-energy CT (DECT) in a phantom study. MATERIALS AND METHODS: In SECT study, phantoms with effective diameters of 9.7, 15.9, 21.1, and 28.5 cm were scanned on SECT scanners of two different manufacturers at a range of tube voltages. Statistical based iterative reconstruction and deep learning reconstruction were used. In DECT study, phantoms with effective diameters of 20, 29.5, 34.6, and 39.7 cm were scanned on DECT scanners from three different manufacturers. VMIs were created from 40 to 140 keV. ICM reduction by lowering kV levels for SECT or switching from SECT to DECT was calculated based on the linear relationship between iodine CNR and its concentration under different scanning conditions. RESULTS: On SECT scanner A, while matching CNR at 120 kV, ICM reductions of 21%, 58%, and 72% were achieved at 100, 80, and 70 kV, respectively. On SECT scanner B, 27% and 80% ICM reduction was obtained at 80 and 100 kV. On the Fast-kV switch DECT, with CNR matched at 120 kV, ICM reductions were 35%, 30%, 23%, and 15% with VMIs at 40, 50, 60, and 68 keV, respectively. On the dual-source DECT, ICM reductions were 52%, 48%, 42%, 33%, and 22% with VMIs at 40, 50, 60, 70, and 80 keV. On the dual-layer DECT, ICM reductions were 74%, 62%, 45%, and 22% with VMIs at 40, 50, 60, and 70 keV. CONCLUSIONS: Our work provided a quantitative baseline for other institutions to further optimize their scanning protocols to reduce the use of ICM.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) remains underdiagnosed and undertreated in girls. Inattentive symptoms, often predominant in girls with ADHD, represent a key driver of impairment and often persist into adulthood. AKL-T01 is a regulated digital therapeutic targeting inattention. We examined potential sex differences in the efficacy of AKL-T01 in three separate trials for 1) children, 2) adolescents, and 3) adults. METHODS: We conducted secondary analyses of clinical outcomes by sex in three AKL-T01 randomized clinical trials in ADHD (n1 = 180 children 30.6% female, M(SD) age = 9.71 (1.32); n2 = 146 adolescents; 41.1% female, M(SD) age = 14.34 (1.26); n3 = 153 adults; 69.9% female, M(SD) age = 39.86 (12.84)). Active treatment participants used AKL-T01 for 25 min/day over 4-6 weeks. Primary outcomes included change in attention on the Test of Variables of Attention (TOVA) and symptom change on the clinician-rated ADHD Rating Scale (ADHD-RS). To evaluate study hypotheses, we conducted a series of robust linear regressions of TOVA and ADHD-RS change scores by sex, adjusting for baseline scores. RESULTS: In children, girls demonstrated greater improvement in objective attention relative to boys following AKL-T01 (TOVA Attentional Composite Score; Cohens d = .36 and Reaction Time Mean Half; Cohens d = .54), but no significant sex differences in ADHD rating scale change. We did not observe significant sex differences in outcomes in the adolescent or adult trials. Limitations include binary sex categorization and slight study design variation across the three samples. CONCLUSION: AKL-T01 might notably improve attentional functioning in girls with ADHD relative to boys. Objective attention measures may be particularly important in the assessment of attentional improvement in childhood, given known gender biases in ADHD symptom reporting. We emphasize the importance of considering sex and gender-specific factors in

U.S. women's age at first birth has increased substantially. Yet, little research has considered how this changing behavior may have affected the motherhood pay penalty, or the wage decrease with a child's arrival, experienced by the current generation. Using Rounds 1-19 of the National Longitudinal Survey of Youth 1997 (NLSY97), in this research note we examine shifts in hourly pay with childbirth for a cohort of women who became mothers mostly in the 2000s and 2010s. Results from fixed-effects models indicate that the motherhood pay penalty for NLSY97 women who had their first child before their late 20s is generally similar to that of previous cohorts. Those who became mothers near or after age 30, however, encounter a parenthood premium, as men do. The growing proportion of women delaying motherhood, coupled with the rising heterogeneity in motherhood wage outcomes by childbearing timing, contributes to a comparatively small motherhood penalty for this recent cohort. The pay advantage of "late mothers" cannot be explained by factors such as their labor market locations, number of children, stage of childrearing, marital status, or ethnoracial composition. Instead, the hourly gain stems from such mothers' tendency to reduce working hours more than other mothers without experiencing a commensurate decrease in total pay. Unlike the fatherhood premium, the premium for late mothers does not lead to a real boost in income.

Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against childrens incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with childrens risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce childrens risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against childrens incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. METHODS AND FINDINGS: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Ea

BACKGROUND AND OBJECTIVE: Prior Epstein-Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS. METHODS: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. Participants were categorized as seropositive and seronegative for EBV-viral capsid antigen (VCA). The association between prior EBV infection and having POMS was estimated with logistic regression. Interactions between EBV serostatus, major HLA MS risk factors, and non-HLA POMS risk variants associated with response to EBV infection were also evaluated with logistic regression. Models were adjusted for sex, age, genetic ancestry, and the mothers education. Additive interactions were calculated using relative risk due to interaction (RERI) and attributable proportions (APs). RESULTS: A total of 473 POMS cases and 702 controls contributed to the analyses. Anti-VCA seropositivity was significantly higher in POMS cases compared to controls (94.6% vs 60.7%, p < 0.001). There was evidence for additive interaction between childhood EBV infection and the presence of the HLA-DRB1*15 allele (RERI = 10.25, 95% confidence interval (CI) = 3.78 to 16.72; AP = 0.61, 95% CI = 0.47 to 0.75). There was evidence for multiplicative interaction (p < 0.05) between childhood EBV infection and the presence of DRB1*15 alleles (odds ratio (OR) = 3.43, 95% CI = 1.06 to 11.07). Among the pediatric MS variants also associated with EBV infection, we detected evidence for additive interaction (p = 0.02) between prior EBV infection and the presence of the GG genotype in risk va

BACKGROUND: According to the Physical Activity Guidelines Advisory Committee Scientific Report, limited evidence is available on sedentary behaviors (screen time) and their joint associations with physical activity (steps) for cardiovascular health in adolescence. The objective of this study was to identify joint associations of screen time and physical activity categories with cardiovascular disease (CVD) risk factors (blood pressure, hemoglobin A1c, cholesterol) in adolescence. METHODS: This study analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, comprising a diverse sample of 4,718 U.S. adolescents aged 10-15 years between 2018 and 2021. Steps were measured by a Fitbit wearable device and levels were categorized as low (1,000-6,000), medium (> 6,000-12,000), and high (> 12,000) averaged daily step counts. Self-reported recreational screen time hours per day were classified as low (0-4), medium (> 4-8), and high (> 8) hours per day. CVD risk factors including blood pressure, hemoglobin A1c, and cholesterol (total and HDL) were measured. RESULTS: The analytical sample averaged 6.6 h of screen time per day and 9,722 steps per day. In models including both screen time and steps, the high screen time category was associated with a 4.27 higher diastolic blood pressure percentile (95% CI 1.83-6.73) and lower HDL cholesterol (B= -2.85, 95% CI -4.77 to -0.94 mg/dL) compared to the low screen time category. Medium (B = 3.68, 95% CI 1.24-6.11) and low (B = 7.64, 95% CI 4.07-11.20) step categories were associated with higher diastolic blood pressure percentile compared to the high step category. The medium step category was associated with lower HDL cholesterol (B= -1.99, 95% CI -3.80 to -0.19 mg/dL) compared to the high step category. Findings were similar when screen time and step counts were analyzed as continuous variables; higher continuous step count was additionally associated with lower total cholesterol (mg/dL). C

Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process. Despite treatment with IV steroids, he deteriorated, manifesting hemiparesis and later impaired consciousness, requiring intubation. A repeat brain MRI demonstrated new bilateral supratentorial lesions associated with venous sinus thrombosis, hemorrhage, and midline shift. Anti-MOG antibody was present at a high titer. CSF IL-6 protein was >2,000 times above the upper limits of normal. He improved after plasma exchange, then began monthly treatment alone with anti-IL-6 receptor antibody, tocilizumab, and has remained stable. This case highlights how adult-onset MOGAD, like childhood ADEM, can rapidly become life-threatening. The markedly elevated CSF IL-6 observed here supports consideration for evaluating CSF cytokines more broadly in patients with acute MOGAD.