Clinical, epidemiological, and care profile of hospitalized patients with retinoblastoma in Brazil

ABSTRACT Purpose: To describe the epidemiological and clinical profile of hospitalized patients with retinoblastoma in Brazil. Methods: Using data from the Hospital Cancer Registry of the Instituto Nacional de Câncer, patients with the morphological codes of retinoblastoma who were diagnosed between 2000 to 2018, aged 0-19 years, and followed up in registered hospitals (analytical cases) were selected. The relative and absolute frequencies of demographic, clinical, diagnostic, therapeutic, and outcome variables were described. Hospital performance indicators were calculated and compared between hospitals qualified and not qualified to treat pediatric oncology cases and between hospitals with different case volumes (<20, 20-75, >75 cases). Results: Of the 2,269 identified analytical cases from 86 institutions, 48% were from the Southeast, 54% were male, and 66% were aged <4 years. The proportion of missing data (NA) was too high for several variables. Approximately 84% of the patients were from the public health system, 40% had a positive family history, and 88% had unilateral involvement. The first treatment included surgery in 58.3% of the patients (NA=2), Approximately 36.6% of these patients achieved complete remission, 10.8% achieved partial remission, and 12.7% died (NA=59%). Hospital performance indicators were within the target in >90% of the patients. The median time between the first appointment and diagnosis (6 days, interquartile range [IQR] 1-14) was significantly lower and the median time to death was longer (343 days, IQR, 212-539) in high-volume hospitals (>75 cases) than in medium- and low-volume hospitals. Conclusions: Despite the high proportion of missing data, we found that the delay in diagnosis is due to prehospital factors. Additionally, there is a need for educational programs for healthcare professionals and families that emphasize early identification and referral to specialized centers. Future studies should focus on the impact of Hospital Cancer Registry data completeness on outcomes, causes of delay in diagnosis, regional inequalities, and barriers to accessing specialized services.

Comparison of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy conducted by pediatric gastroenterologists.

Objectives: The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared. Methods: We retrospectively analyzed the cases of pediatric patients (≤15 years old) who had undergone bidirectional endoscopy, esophagogastroduodenoscopy, and colonoscopy by pediatric gastroenterologists. Demographic data, indications, sedatives/dosages, clinical outcomes, endoscopic findings, adverse events, and total patient time requirements (total time in which patients stay in our hospital) were compared in the two sedation groups. Results: Ninety-one children (51 boys, 40 girls, mean age 13 years, range 9-15) treated at our hospital were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was administered to 51 patients (propofol-based sedation group). Midazolam alone or in combination with pentazocine was administered to the other 40 patients (midazolam sedation group). In the propofol group, the following mean doses were used: propofol, 96 mg (range 40-145 mg); midazolam, 4.9 mg (range 3-5 mg); and pentazocine, 7.5 mg. In the midazolam group, the mean doses of midazolam and pentazocine were 6.2 mg (range 4-10 mg) and 15 mg, respectively. All procedures were successfully completed by pediatric gastroenterologists. The total procedure times and endoscopic findings were similar in the two groups, but the median patient time requirement in the propofol group was significantly shorter versus the midazolam group (7.3 h vs. 8.4 h, p < 0.001). No adverse events occurred in either group. Conclusions: Propofol-based sedation in pediatric bidirectional endoscopy was safely and effectively performed by pediatric gastroenterologists, and its patient time requirement was shorter than that for midazolam sedation.

Multi-informant evaluation of Cognitive Disengagement Syndrome (formerly Slow Cognitive Tempo). Children's self-reported measures in relation to parents / Evaluación multi-informante del Síndrome de Desconexión Cognitiva (anteriormente Tempo Cognitivo Lento). Medidas autoinformadas de los niños con relación a padres

El objetivo fue examinar, desde una aproximación multi-informante, las medidas del Síndrome de Desconexión Cognitiva (SDC) de padres/madres e hijos/as y su relación con síntomas internalizantes y externalizantes. 279 niños/as (9-13 años), y sus padres/madres completaron las evaluaciones sobre SDC, la inatención del trastorno por déficit de atención e hiperactividad (TDAH) y otras medidas internalizadas y externalizadas. Los ítems de las tres medidas de SDC convergieron razonablemente bien en el factor SDC. Se aportaron pruebas discriminantes de la validez de las relaciones entre las puntuaciones de las pruebas y las medidas de los tres constructos diferentes (SDC, soledad y preferencia por la soledad). La asociación más estrecha estuvo entre la evaluación parental de las medidas de SDC con ansiedad y depresión, y entre inatención con hiperactividad/impulsividad y trastorno negativista desafiante. Se observó capacidad predictiva de la medida de SDC sobre la soledad y preferencia por estar solo autoinformadas. Se encontró una posible asociación entre la medida del SDC evaluado por padres/madres y sexo y edad de los niños. En conclusión, los datos apoyan la inclusión de medidas autoinformadas en la evaluación del SDC. Las medidas del SDC en niños se vinculan con medidas internalizantes y, la inatención con las externalizantes.(AU)

Management of aortic disease in children with FBN1-related Marfan syndrome.

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000-1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients. Prompt diagnosis, appropriate follow-up, and timely treatment can prevent aortic events. Currently there are no specific recommendations for treatment of children with MFS, and management is greatly based on adult guidelines. Furthermore, due to the scarcity of studies including children, there is a lack of uniform treatment across different centres. This consensus document aims at bridging these gaps of knowledge. This work is a joint collaboration between the paediatric subgroup of the European Network of Vascular Diseases (VASCERN, Heritable Thoracic Aortic Disease Working Group) and the Association for European Paediatric and Congenital Cardiology (AEPC). A group of experts from 12 different centres and 8 different countries participated in this effort. This document reviews four main subjects, namely, (i) imaging of the aorta at diagnosis and follow-up, (ii) recommendations on medical treatment, (iii) recommendations on surgical treatment, and (iv) recommendations on sport participation.

Effectiveness of a Mobile App (Meds@HOME) to Improve Medication Safety for Children With Medical Complexity: Protocol for a Randomized Controlled Trial.

BACKGROUND: This study will pilot-test the mobile app, Medication Safety @HOME-Meds@HOME intervention to improve medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management for children with medical complexity (CMC). The Meds@HOME app was co-designed with CMC families, secondary caregivers (SCGs), and health professionals to support medication management for primary caregivers (PCGs) and SCGs of CMC. We hypothesize that Meds@HOME will improve caregivers' medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management. OBJECTIVE: This study aims to evaluate the effectiveness of Meds@HOME on medication administration accuracy for PCGs and SCGs. METHODS: This study will recruit up to 152 PCGs and 304 SCGs of CMC who are prescribed at least 1 scheduled high-risk medication and receive care at the University of Wisconsin American Family Children's Hospital. PCGs will be randomly assigned, for the 6-month trial, to either the control group (not trialing Meds@HOME) or the intervention group (trialing Meds@HOME) using 1:1 ratio. The Meds@HOME app allows caregivers to create a child profile, store medication and care instructions, and receive reminders for upcoming and overdue care routines and medication refills. Surveys completed both at the start and end of the trial measure demographics, medication delivery knowledge, confidence in the CMC's caregiving network, and comfort with medical information. Univariate and multivariate generalized estimation equations will be used for primary statistical analysis. The primary outcome is the PCG's rate of medication administration accuracy measured as correct identification of each of the following for a randomly selected high-risk medication: indication, formulation, dose, frequency, and route at baseline and after 6 months. Secondary outcomes include SCG medication administration accuracy (indication, formulation, dose, frequency, and route), count of University of Wisconsin hospital and emergency department encounters, PCG-reported medication adherence, count of deaths, and PCG medication confidence and understanding. RESULTS: Recruitment for this study began on November 29, 2023. As of May 15, 2024, we have enrolled 94/152 (62%) PCGs. We expect recruitment to end by August 1, 2024, and the final participant will complete the study by January 28, 2025, at which point we will start analyzing the complete responses. We expect publication of results at the end of 2025. CONCLUSIONS: The Meds@HOME mobile app provides a promising strategy for improving PCG medication safety for CMC who take high-risk medications. In addition, this protocol highlights novel procedures for recruiting SCGs of CMC. In the future, this app could be used more broadly across diverse caregiving networks to navigate complex medication routines and promote medication safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT05816590; https://clinicaltrials.gov/study/NCT05816590. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60621.

The relationship between sphingomyelin and ceramide levels and soft neurological signs in ADHD.

Attention deficit hyperactivity disorder (ADHD), characterized by attention deficit, hyperactivity, and impulsivity, has recently been associated with lipid metabolism. In particular, the roles of sphingomyelin, ceramide, andgalactosylceramidase in the pathophysiology of ADHD are being investigated. This study aims to explore the relationship between sphingolipid metabolism markers and soft neurological signs (SNS) in children diagnosed with ADHD who are not undergoing medication treatment. A cross-sectional analysis was conducted on 41 children and adolescents aged 7-12 years diagnosed with ADHD and 39 neurotypically developing controls. Plasma levels of ceramide, sphingomyelin, and galactosylceramidase were measuredusing Enzyme-Linked Immunosorbent Assay (ELISA). SNS were assessed using the Physical and Neurological Examination for Soft Signs (PANESS). Statistical analyses included Student's t-tests, Mann-Whitney U tests, and Multivariate Analysis ofCovariance (MANCOVA), along with logistic regression analysis. Plasma levels of ceramide and sphingomyelin in children with ADHD showed significant differences compared to the neurotypically developing control group; however, there were no significant differences in galactosylceramidase levels between the two groups. Positive correlations were found between plasma levels of ceramide and sphingomyelin and the PANESS subscales F1 (Total Gait and Station) and F3 (Total Dysrhythmia). Additionally, logistic regression analysis indicated that high ceramide levels were positively associated with ADHD. This study underscores a significant association between alterations in sphingolipid metabolism (specifically increased levels of ceramide and sphingomyelin) and the presence of SNS in children with ADHD. These findings elucidate the potential role of sphingolipid metabolism in the pathophysiology of ADHD and provide suggestions for future therapeutic research targeting sphingolipid metabolism in the treatment of ADHD.

The Richness of Reports Provided by Children in Israel: Examination of the Impact of Social Affiliations.

Forensic interviews following child sexual abuse (CSA) are of central importance to the children, their families and all those involved. Moreover, the legal system expects rich, forensically relevant reports from the children. The current study focuses on the impact of children's social affiliation on the richness of their reports, and how question types contribute to rich reports. The sample included 314 forensic interviews conducted in Israel between 2015 and 2018. The findings revealed a relationship between child characteristics (gender), abuse characteristics (perpetrator identity, abuse type, abuse frequency) and social affiliation with report richness. Furthermore, question types (free recall prompts, summaries, directive, option-posing, suggestive) moderated the relationship between the child's characteristics, abuse characteristics, and social affiliation with report richness, when these effects were not equal. The findings emphasized that contextual observation of sexually abused children may promote better services for them and, in addition, stressed the importance of advancing future training and practical guidelines for practitioners.

Human adenovirus type 4 (HAdV-4) associated acute respiratory tract infection in children & genetic characteristics of HAdV-4 in China: a prospective multicenter study.

BACKGROUND: Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. METHODS: Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. RESULTS: There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. CONCLUSIONS: The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs.

Low-carbohydrate diet in children and young people with type 1 diabetes: A randomized controlled trial with cross-over design.

AIMS: We investigated whether a short period of tightly controlled low-carbohydrate diet (LCD) leads to higher time in range without increasing the associated risks in children and young people with diabetes (CYPwD). METHODS: Thirty-five (CYPwD) were recruited into this randomized controlled cross-over study (20 female; 20 CSII; age 14.5 ± 2.9 years; HbA1c 48.9 ± 9.4 mmol/mol). The interventions were five and five weeks of ready-made food box deliveries of isocaloric diets in random order: either LCD (94.5 ± 4.7 g/day) or recommended carbohydrate diet (RCD) (191 ± 19.2 g/day). The outcomes were continuous glucose monitoring parameters, anthropometric, laboratory and quality of life (QoL) data. RESULTS: Time in range was significantly higher in the LCD than in the RCD period (77.1 % vs. 73.8 %, P=0.008). Times in hyperglycemia and average glycaemia were significantly lower in the LCD. There was no difference between the diets in time in hypoglycemia or glycemic variability. The subjects' body weight and BMI were significantly lower during the LCD. There was no significant difference in the LDL-cholesterol levels. No significant differences were observed in the self-assessed QoL. CONCLUSIONS: Short-term LCD led to an improvement of glycemic parameters without increasing time in hypoglycemia, disturbing the lipid profile or negatively affecting the quality of life of CYPwD.

Exhaled volatile organic compounds (VOCs) for prediction of asthma exacerbation in children.

OBJECTIVES: To find possible relationship between asthma exacerbation and metabolomic profile of airways, assessed by non-invasive method - free volatile organic compounds (VOCs) in exhaled air in children. MATERIAL AND METHODS: The study included 80 children aged 4-18 years with asthma: 42 children with a min. 3 asthma exacerbations in the past 12 months, and 38 children without a history of exacerbations in the past year. During the study visit, each patient was examined, medical history (including information regarding atopy and eosinophil blood count) was taken, spirometry and fractional exhaled nitric oxide (FeNO) were tested, an exhaled air sample was taken to test for the presence of VOCs, and the patient also completed standardized form - Asthma Control Questionnaire. Volatile organic compounds were measured by combined gas chromatography coupled to mass spectrometry. RESULTS: The obtained results of VOCs were correlated with the history of the disease. The 2 gas profiles were defined and they formed 2 clinically distinct clusters (p = 0.085). Cluster 2 was characterized for children with a higher number of bronchial asthma exacerbations and worse lung function parameters (predicted percentage forced expiratory volume in 1 s [FEV1] [p = 0.023], FEV1/ forced vital capacity ratio [FVC] [p = 0.0219]). The results were independent of the age, sex, BMI, atopy (house dust mite allergy) and eosinophil blood count. CONCLUSIONS: The study findings suggest that a relative group of gases may be a useful predictor of having asthma exacerbations in children. Additionally, a single FeNO value was unlikely to be clinically useful in predicting asthma exacerbations in children. The VOCs profile reflecting the metabolism of the airway epithelium and local microbiota was associated with the course of asthma, which strongly justifies further prospective validation studies. Int J Occup Med Environ Health. 2024;37(3):351-59.

Thoracoabdominal aortic replacement in a 6-year-old boy with Loeys-Dietz syndrome.

Connective tissue disorders such as Marfan- and Loeys-Dietz syndrome (LDS) can lead to aortic aneurysms and aortic dissections in children. Patients with LDS often necessitating multiple aortic surgeries throughout their lives to extend their lifespan. A boy with LDS underwent Bentall procedure at the age of three for aortic aneurysm. At the age of six, this boy was referred to the hospital again due to severe abdominal pain. Computed tomographic angiography (CTA)indicates aortic dissection (DeBakey Type III, Stanford Type B). After a multidisciplinary team discussion, a successful thoracoabdominal aortic replacement was performed.

Remote electrical neuromodulation to treat children and adolescents with migraine in the emergency department: A randomized double-dummy pilot trial.

OBJECTIVE: Using a double-dummy pilot randomized controlled trial design, we aimed to determine the feasibility and acceptability of comparing remote electrical neuromodulation (REN) to typical care intravenous pharmacologic interventions for the treatment of children and adolescents visiting the emergency department (ED) with migraine, and to compare parallel-group versus crossover trial designs. BACKGROUND: There are limited data to guide the management of migraine in the ED. Children and adolescents are interested in neuromodulation, and specifically REN, for treatment in this setting, but there are no existing data on this approach. METHODS: We employed a double-dummy, double-blind, pilot randomized controlled trial that tested two designs in two phases: a parallel-group design and a crossover design (ClinicalTrials.gov identifier: NCT05102591). The intervention arms consisted of: (i) active REN stimulation with matched normal saline placebo intravenously, and (ii) matched sham REN stimulation, intravenous metoclopramide (0.15 mg/kg, maximum 10 mg), and intravenous ketorolac (0.5 mg/kg, maximum 30 mg). Youth aged 8.0-<18.0 years visiting a Canadian tertiary care pediatric ED with migraine attacks as per criteria B-E of the International Classification of Headache Disorders third edition were eligible. Primary outcomes were focused on trial feasibility and acceptability, and preliminary efficacy and safety data were also collected. RESULTS: A total of 34% (22/65) of those who screened eligible were enrolled. Three participants (14%) withdrew prior to receiving any study interventions. In all, 10 participants were allocated to typical care, and nine to REN. All treated participants (19/19) completed all assessments. Recruitment was higher during the parallel-group phase: 1.1 participants/month versus 0.6 participants/month, and 36% (17/47) versus 28% (five of 18) of screened eligible were enrolled in the parallel-group and crossover phases, respectively. Participants reported positive impressions of REN use in the ED, e.g., higher mean (standard deviation [SD]) levels of interest in using REN only at 3.7 (1.0) versus 2.8 (1.0) in using intravenous interventions only for a future ED visit. Participants and clinical staff reported overall positive impressions regarding the study protocol. Employing an 11-point pain numerical rating scale, the mean (SD) reduction in pain severity score was 2.1 (1.3) and 2.9 (2.9) from baseline to 1 h, and 2.4 (1.6) and 4.0 (3.5) from baseline to 2 h for REN and intravenous interventions, respectively. One participant in the typical care group and none in the REN group experienced adverse events. CONCLUSION: We demonstrated the feasibility and acceptability of our trial protocol and of using REN to treat youth presenting to the ED with migraine. The parallel-group design generated a higher recruitment rate than the crossover design. Our preliminary efficacy and safety data suggest that REN could be non-inferior to typical care, but we were not powered for these outcomes. Further research on REN's use in the ED setting is warranted.

Omalizumab reduces anaphylactic reactions and allows food introduction in food-allergic in children with severe asthma: An observational study.

BACKGROUND: In Europe, Omalizumab (anti-IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE-mediated food allergy (FA). OBJECTIVE: We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA-QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. METHODS: Food-allergic children (6-18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4-month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food-allergic reactions, Asthma Control Test (ACT) scores, FA-QoL, and total IgE levels. RESULTS: In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243- and 488-fold for fresh and baked milk, respectively; 172- and 134-fold for raw and baked egg; 245-fold for hazelnut; 55-fold for peanut; 31-fold for wheat; and 10-fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety-five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1-Q3: 15-17) to 23.6 (Q1-Q3: 23-25). The FA-QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50. CONCLUSIONS: During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT06316414.

Environmental toxicants modulate disease severity in pediatric metabolic dysfunction-associated steatohepatitis.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in children. We hypothesized environmental toxins could drive progression to metabolic dysfunction-associated steatohepatitis (MASH), and assayed serum toxins and metabolites in children with histologically characterized MASLD/MASH. METHODS: Environmental chemicals, common in household items, perfluoroalkyl substances (PFAS), brominated flame retardants (PBDEs), and metabolic profiles were assayed in children enrolled in the multicenter NASH Clinical Research Network Pediatric Database 2. Mixture models, using repeated holdout weighted quantile sum regression (WQSrh) were run in addition to single chemical/metabolite logistic regression. For metabolomic analyses, random subset version of WQSrh was used for the large number of predictors versus participants. Nominal and false discovery rate (FDR) p-values (two-sided) were computed. RESULTS: Four hundred and thirty-five children distributed across MASH (n = 293) and MASLD (n = 142), with 304 (69.9%) males. Mean (standard deviation) for Nonalcoholic Steatohepatitis Score (NAS) and alanine aminotransferase (ALT) for MASLD were 3.1 (1.0), 67.9 (43.4), and for MASH 4.2 (1.4), 144 (121). There was an inverse association between PFAS/PBDE mixture and MASH versus MASLD, lobular inflammation (p = 0.026), NAS (p = 0.009, FDR p = 0.04), and log-transformed ALT (p = 0.005, FDR p = 0.025) driven by perfluorohexane sulfonate (PFHxS). Metabolites from positive hydrophilic interaction liquid chromatography mode, biliverdin (p = 0.002) and 1-methylhistidine (associated with meat ingestion, p = 0.02) and reverse phase negative mode, hippuric acid (solvent exposure, p = 0.022) significantly associated with MASH. CONCLUSIONS: Significant negative PFAS/PBDE mixture effect and odds of MASH were dominated by PHFXS. Several metabolites are significantly associated with MASH which inform mechanistic pathways and could drive key therapeutic and diagnostic strategies in children.

Efficient use of mepolizumab in children: An analysis of the economically justifiable price in Colombia.

INTRODUCTION: Asthma imposes a crucial economic burden on health systems, especially with the incorporation of new drugs. Recently, mepolizumab has been approved to prevent exacerbations in patients with eosinophilic asthma. This study explores the economically justifiable price of mepolizumab for preventing exacerbations in children with severe asthma. MATERIALS AND METHODS: A model was developed using the microsimulation to estimate the quality-adjusted costs and life years of two interventions: mepolizumab versus not applying standard treatment without mepolizumab. This analysis was made during a time horizon of 50 years and from a third-payer perspective. RESULTS: Mepolizumab was cost-effective using a WTP of U$ 19,992 per QALY, but not at a WTP of U$ 4828, U$ 5128 per QALY. The economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of U$ 4828, and U$ 5128 respectively. At the current price of Mepolizumab, U$ 780 per dose, only using a WTP higher than U$ 10,300 per QALY mepolizumab will be the best alternative to no mepolizumab. CONCLUSION: Our study shows that the economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of 4828 and 5180 respectively. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Early-pregnancy BMI, maternal gestational weight gain, and asthma and allergic diseases in children.

BACKGROUND: Association of early pregnancy body mass index (BMI) and maternal gestational weight gain (GWG), and asthma and allergic disease in children is unclear. METHODS: We analyzed data from 3176 mother-child pairs in a prospective birth cohort study. Maternal anthropometric measurements in the first and last antenatal clinic visits were obtained through post-delivery questionnaires to calculate early pregnancy BMI and maternal GWG. Asthma and allergic diseases in children by the age of 5 years was assessed using a validated questionnaire. Furthermore, serum samples were analyzed for IgE antibodies to eight allergens. We applied Cox proportional hazards and logistic regression analyses to estimate the association of early pregnancy BMI and maternal GWG (as continuous variables and categorized into quarters), and asthma, atopic eczema, atopic sensitization, and allergic rhinitis in children. RESULTS: Neither early pregnancy BMI nor maternal GWG was associated with asthma and allergic disease in children when analyzed as continuous variables. However, compared to the first quarter of GWG (a rate <0.32 kg/week), mothers in the third quarter (rate 0.42-0.52 kg/week) had children with significantly higher odds of developing atopic eczema (adjusted OR 1.49, 95% CI [1.13-1.96]) by 5 years of age. CONCLUSION: Association of early pregnancy BMI and maternal GWG, and asthma and allergic disease in children, is inconsistent. High maternal GWG may be associated with increased odds of atopic eczema.

Heart rate to identify non-febrile children with dehydration and acute kidney injury in emergency department: a prospective validation study.

We previously developed and retrospectively validated the estimated percentage of heart rate variation (EHRV) as a predictor of the composite outcome of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile children. The current study aimed to prospectively validate EHRV as a predictor for dehydration or AKI in a different cohort of children attending the Pediatric Emergency Department. From July 2022 to August 2023, 256 pediatric patients aged 0-18 years attending the Pediatric Emergency Department were enrolled. EHRV was calculated as follows: [(HR at admission - 50th percentile of HR for age and sex)/HR at admission] × 100. Dehydration was categorized as < 5% or ≥ 5% fluid deficit. AKI was defined according to KDIGO creatinine criteria. Statistical analyses included receiver-operating characteristic (ROC) curves and logistic regression analysis. Among enrolled patients, 52 had ≥ 5% dehydration, 50 had AKI, and 16 had both conditions. EHRV demonstrated significant predictive ability for both ≥ 5% dehydration (AUROC = 0.71; 95% confidence interval (CI), 0.63-0.78; p < 0.001) and AKI (AUROC = 0.78; 95% CI, 0.71-0.84; p < 0.001). An EHRV > 24.5% was associated with an increased odds ratio (OR), adjusted for confounders, of ≥ 5% dehydration (OR = 3.5; 95% CI, 1.6-8.0; p = 0.003) and AKI (OR = 3.4; 95% CI, 1.6-7.3; p = 0.002). The sensitivity and specificity of this cut-off were 34% and 83% for ≥ 5% dehydration and 36% and 84% for AKI, respectively. CONCLUSIONS: This study prospectively validates the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. An EHRV > 24.5% could serve as a marker for suspecting dehydration or AKI. Further validation across diverse patient populations and settings is needed. WHAT IS KNOWN: • An increased heart rate (HR) is a readily detectable sign of dehydration in children. • In a retrospective validation cohort, an estimated HR variation (EHRV) greater than 24.5% compared to the 50th percentile of HR was predictive of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile patients. WHAT IS NEW: • We prospectively validated the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. • We confirmed that an EHRV greater than 24.5% is associated with increased odds of ≥ 5% dehydration and AKI.

Risk of depression in patients with atopic dermatitis: An updated systematic review and meta-analysis of children, adolescent and adult groups.

AIM: Atopic dermatitis is a popular allergy disease among children, adolescents and adults. The risk of depression in patients with atopic dermatitis can be evaluated using an updated systemic review and meta-analysis of observational and cross-sectional studies. METHODS: The log odds ratio (OR) was transformed using the OR and 95% confidence interval (CI) to assess the risk of depression in patients with atopic dermatitis across the children, adolescent and adult groups. After a restricted selection, 39 studies of 234 306 patients with atopic dermatitis and 10 935 459 reference individuals were enrolled. The focused outcome was the OR and 95% CI of depression risk in each included study, assigned according to the age for the children, adolescent and adult groups. RESULTS: In adult patients with atopic dermatitis, a significantly higher risk of depression was observed. In addition, the similar significantly higher risk of depression was observed in children and adolescent patients with atopic dermatitis, respectively. However, the significantly high heterogeneity was observed across children, adolescent and adult groups. CONCLUSIONS: In the current meta-analysis, the patients with atopic dermatitis had a higher risk of depression across the children, adolescent and adult groups, respectively. However, substantial heterogeneity should be considered during the interpretation of our meta-analysis results.

3D printed personalized therapies for pediatric patients affected by adrenal insufficiency.

BACKGROUND: Adrenal insufficiency is usually diagnosed in children who will need lifelong hydrocortisone therapy. However, medicines for pediatrics, in terms of dosage and acceptability, are currently unavailable. RESEARCH DESIGN AND METHODS: Semi-solid extrusion (SSE) 3D printing (3DP) was utilized for manufacturing of personalized and chewable hydrocortisone formulations (printlets) for an upcoming clinical study in children at Vall d'Hebron University Hospital in Barcelona, Spain. The 3DP process was validated using a specific software for dynamic dose modulation. RESULTS: The printlets contained doses ranging from 1 to 6 mg hydrocortisone in three different flavor and color combinations to aid adherence among the pediatric patients. The pharma-ink (mixture of drugs and excipients) was assessed for its rheological behavior to ensure reproducibility of printlets through repeated printing cycles. The printlets showed immediate hydrocortisone release and were stable for 1 month of storage, adequate for prescribing instructions during the clinical trial. CONCLUSIONS: The results confirm the suitability and safety of the developed printlets for use in the clinical trial. The required technical information from The Spanish Medicines Agency for this clinical trial application was compiled to serve as guidelines for healthcare professionals seeking to apply for and conduct clinical trials on 3DP oral dosage forms.

Comparison of clinical characteristics and severity of COVID-19 with or without viral co-infection in hospitalized children.

BACKGROUND: Co-infection with other pathogens can alter the severity and clinical outcomes of viral infections. However, the information regarding viral co-infections in pediatric coronavirus disease 2019 (COVID-19) cases is still limited. METHODS: This is a nationwide, retrospective cohort study using the data from the COVID-19 Registry Japan. The pediatric (<18 years), laboratory confirmed, hospitalized COVID-19 patients in the Omicron variant of concern predominant period (January 2022 to January 2024) were included. Co-infection was investigated by multiplex PCR. We compared clinical characteristics, symptoms, severity, and outcomes between children with and without co-infection. RESULTS: Among 245 hospitalized pediatric COVID-19 patients, 78 (31.8 %) had co-infections. The patient backgrounds of the "co-infection" and "SARS-CoV-2 alone" groups were similar, although age distribution was different, with a lower number of patients over 12 years in the co-infection group (n = 2, 2.6 % vs. n = 29, 17.4 %; P < 0.001). Among the patients with co-infection, the most common pathogen was enterovirus/rhinovirus (51.3 %), followed by parainfluenza virus (23.1 %) and adenovirus (12.8 %). Patients with co-infection more commonly had respiratory symptoms, including SpO2 < 96 %, shortness of breath, runny nose, and wheezing. Requirement of non-invasive oxygen support was higher in the co-infection group (n = 27, 34.6 % vs. n = 28, 16.8 %, P = 0.006). By multivariable logistic regression analysis, co-infection and presence of any comorbidity were identified as significant risk factors for necessity of oxygen therapy (odds ratio [95 % confidence interval] 2.44 [1.29-4.63] and 3.99 [2.07-7.82], respectively). CONCLUSIONS: Viral co-infection may increase the risk of respiratory distress in pediatric COVID-19 patients.