Medicine and Pharmacology

Abstract: Preterm and critically ill infants rely on plastic-containing medical systems for respiratory support, nutrition, vascular access, medication delivery, and monitoring. These systems are potential sources of microplastic (MP) exposure, although evidence varies by route. This narrative review examines intravascular, enteral, and respiratory exposure in neonatal intensive care unit (NICU) and considers how to measure and interpret these exposures in neonates. Evidence is strongest for the intravascular pathway, more limited for the enteral pathway, and currently insufficient to characterize either device-derived respiratory exposure or ambient-air exposure in the NICU. Across all three pathways, differences in analytical methods, particle-size ranges, contamination control, and source attribution make it difficult to determine what particles reach the infant and where they originate. Interpretation is further complicated because the most premature and critically ill infants receive the most intensive and prolonged device-dependent care. This makes it difficult to separate treatment-associated exposure from the effects of prematurity and illness severity, which also determine treatment intensity and influence neonatal outcomes. Addressing this problem will require quantitative studies that determine what particles reach the infant, identify their sources, and assess whether they are also detected in neonatal specimens.

Abstract: Background: India has the largest number of preterm births in the world, roughly 3 million a year, and about one in six newborns is born with low birth weight (LBW). Preterm birth and LBW reduce nephron endowment and roughly double the lifetime risk of chronic kidney disease (CKD). Yet structured kidney follow-up of neonatal intensive care unit (NICU) and special newborn care unit (SNCU) graduates is rare in India, and no risk stratification tool exists for this population. Aim: To review the evidence linking preterm birth and LBW to CKD, describe the Indian care pathway for at-risk infants, draw on recent clinician-perspective research on clinical decision support (CDS) tools, and propose an India-adapted framework for CKD risk prediction in children. Key points: (1) Risk factors that can be captured at NICU/SNCU discharge — gestational age, birth weight, small-for-gestational-age status, neonatal acute kidney injury, nephrotoxic drug exposure, and congenital anomalies of the kidney and urinary tract (CAKUT) — allow simple tiered risk stratification. (2) International data show clinicians want CDS tools that fit workflow, integrate with records and give actionable advice with family education. (3) In India, paper-based discharge summaries, the Mother and Child Protection Card, Rashtriya Bal Swasthya Karyakram (RBSK) and the Ayushman Bharat Digital Mission (ABDM) offer practical delivery routes. (4) Low-cost tests — blood pressure, urine dipstick for protein, serum creatinine with bedside Schwartz eGFR — suit resource-limited follow-up. (5) Over-referral to scarce paediatric nephrologists and false reassurance must be designed against. Conclusion: A tiered, low-cost, family-centred CKD risk tool for children born preterm or LBW is feasible in India and is needed. We outline a research agenda, starting with a multi-stakeholder qualitative study of Indian clinicians and families.

Abstract: Background: Short-course antibiotic therapy is increasingly recommended for children with uncomplicated community-acquired pneumonia (CAP), but uncertainty remains about its applicability to bacterial disease and whether antibiotics are needed in routine pediatric outpatient care settings. Methods: We conducted a narrative review of literature published from January 2010 through September 2026. PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, agency websites, and reference lists were searched. Evidence was synthesized descriptively; no formal risk-of-bias assessment or meta-analysis was performed. Results: Systematic reviews and randomized trials indicate that three- to six-day courses can achieve outcomes comparable to longer regimens in children, mainly outpatients with mild, uncomplicated CAP. However, many trials relied on clinical diagnosis, rarely established etiology, and excluded children with severe disease or major comorbidities. Inclusion of children without bacterial infection may have contributed to similar outcomes across treatment durations; evidence is insufficient to establish efficacy in confirmed bacterial CAP or higher-risk populations. Shorter courses reduce antibiotic exposure among treated children but do not determine who needs antibiotics. Lung ultrasound offers a radiation-free point-of-care approach to identifying pneumonia, while procalcitonin and rapid viral testing may refine etiological assessment. Yet evidence for combined diagnostic strategies largely concerns accuracy rather than outpatient prescribing outcomes. Conclusions: Short courses are supported for carefully selected children with uncomplicated CAP, but their generalizability is limited. Improving diagnosis and identifying children likely to benefit from antibiotics may reduce unnecessary use beyond what shortening treatment alone can achieve. Prospective outpatient studies should evaluate whether integrated imaging, biomarkers, and microbiological tests improve prescribing and clinical outcomes.

Abstract: Introduction: Proctalgia fugax (PF) is an anorectal disorder characterized by sudden, transient episodes of rectal pain. Although it has traditionally been described in adults, its recognition in pediatrics has gained relevance with its inclusion in the Rome V Criteria. Objective: To determine the prevalence of PF according to the Rome IV Criteria for adults modified for pediatrics, in schoolchildren and adolescents attending a Public School in Cali, Colombia. Methods: An observational, descriptive, cross-sectional study was conducted in schoolchildren and adolescents aged 10–18 years. Demographic, clinical, and socioaffective variables were collected. Questionnaires were administered to identify disorders of gut-brain interaction (DGBIs) (QPGS-IV), quality of life (PedsQL), and anx-iety/depression (PROMIS-Anxiety/PROMIS-Depression). PF was defined using the Rome IV Criteria for adults modified for pediatrics. Statistical analysis included measures of central tendency and the chi-square or Fisher's exact test, with p< 0.05 considered statis-tically significant. Results: A total of 199 schoolchildren and adolescents were included (mean age 14.3 ± 2.0 years; 75.4% adolescents; 53.8% male; 39.7% mixed race). Regarding socioaffective variables, 65.8% had separated or divorced parents; school and social ab-senteeism were present in 43.2% and 34.2%, respectively; impaired quality of life in 53.8%; anxiety in 35.2%; and depression in 37.2%. The prevalence of any DGBI was 28.1%, defecation-related DGBIs 16.6%, and PF 3.0%. None of the variables analyzed showed significant differences for PF, except anxiety (p=0.002). Conclusions: PF was identified in 3.0% of the participants, showing that it can occur in schoolchildren and adolescents, with anxiety being an important factor to consider.

Abstract: Introduction: Iron deficiency during pregnancy and early childhood may affect myelination, neurotransmission, and neural network maturation, with potential consequences for motor, cognitive, and language development. Objective: To quantitatively synthesize the effects of iron supplementation on motor, cognitive/global, and language development by integrating the original dataset with a complementary search for original studies. Methods: Systematic review with random-effects quantitative synthesis. The expanded review included 11 publications. Continuous outcomes and adjusted estimates were harmonized to log odds ratios (logOR), with positive values indicating better performance with greater iron exposure. Between-study variance was estimated by restricted maximum likelihood (REML). Ten motor, 11 cognitive/global, and 7 language effect estimates were pooled. Results: For motor development, the pooled effect was logOR 0.31 (95% CI 0.14 to 0.48; OR 1.36; p < 0.001; τ² = 0.044; I² = 69.3%). For cognitive/global development, the pooled effect was logOR 0.11 (95% CI -0.10 to 0.33; OR 1.12; p = 0.307; τ² = 0.088; I² = 74.8%). For language, the pooled effect was logOR -0.02 (95% CI -0.26 to 0.21; OR 0.98; p = 0.851; τ² = 0.048; I² = 50.7%). Conclusion: The expanded synthesis yielded a positive pooled estimate for motor development, whereas pooled cognitive/global and language estimates remained close to the null. Effect magnitude and direction varied across populations, timing and dose of supplementation, baseline iron status, and age at assessment.

Abstract: Background: Perinatal asphyxia is a critical condition resulting from various complications around birth. Despite advances in neonatal care reliable prediction of long-term neurodevelopmental outcomes remains challenging. Therefore, standardized clinical follow-up assessments are recommended to detect impairments early and provide optimal support. This study aimed to characterize five-year neurodevelopmental outcomes in children with history of perinatal asphyxia treated at a tertiary neonatal care center in Austria. Methods: This retrospective analysis included infants with perinatal asphyxia, defined as umbilical artery pH < 7.0, admitted to the neonatal intensive care unit in Graz, Austria, between January 2004 and September 2020. The primary outcome was neurodevelopmental status at five years of age. This was assessed by trained clinicians during routine follow-up examinations and classified as age-appropriate development or mild, moderate, or severe developmental delay. Where feasible, the intelligence quotient was additionally quantified by certified psychologists using the standardized Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Demographic characteristics, causes of asphyxia, neonatal clinical course and short-term outcomes were also assessed. Data were extracted from the local electronic patient documentation system and analyzed descriptively. Results: Of 139 eligible neonates, 25 (18%) died. Five-year follow-up data were available for 35 (31%) of the 114 survivors, their median gestational age was 36.6 (IQR 31.3–39.3) weeks; 16 (46%) were term infants and 19 (54%) preterm infants. Hypoxic-ischemic encephalopathy was diagnosed in 19 (54%) infants. 10 (29%) infants received therapeutic hypothermia, and 30 (86%) required invasive respiratory support. At five years, five (31%) term infants achieved age-appropriate development, while five (31%) had mild, three (19%) moderate, and three (19%) severe developmental delay. Among preterm infants, four (21%) showed age-appropriate development, whereas 10 (53%) had mild, three (16%) moderate, and two (11%) severe developmental delay. Conclusion: Developmental delay was common among both term and preterm infants assessed five years after perinatal asphyxia. However, the small cohort and incomplete follow-up limit the generalizability of these findings. Improved strategies for risk stratification, neuroprotective interventions and long-term developmental surveillance are warranted.

Abstract: The neutropenic diet (ND), also called a low-bacterial or low-microbial diet, is widely used in pediatric oncology and hematology to reduce the risk of presumed foodborne infection. Practices vary among centers, and its effectiveness remains debated. This narrative review aimed to assess the ND’s effectiveness, feasibility, health outcomes, and risks in pediatric hematologic and oncologic populations. Available pediatric evi-dence has not established a consistent infection-prevention benefit over standard food safety practices. Evidence remains limited, and findings in adults, including high-risk patients, cannot be directly generalized to children. The review also identifies potential costs of restrictive diets. Excluding foods such as fresh produce and limiting dietary variety may reduce palatability and energy intake, compromise nutrient and fiber in-take, and affect nutritional status. Dietary restrictions may burden families and inter-fere with children’s food preferences and social experiences. Possible effects on the gut microbiome and intestinal barrier warrant further study; current evidence does not establish these as clinical outcomes of ND in children. Overall, routine ND use in pedi-atric patients is not supported by evidence of superior infection prevention and may impose avoidable nutritional and psychosocial burdens. The review favors careful food handling and hygiene, alongside adequate intake and individualized nutritional sup-port, over blanket food-group exclusions. Clinicians should consider treatment, neu-tropenia duration and severity, nutritional status, and family context. Patients at par-ticularly high risk, including some undergoing hematopoietic stem cell transplantation or experiencing prolonged neutropenia, may need tailored precautions. Further pedi-atric research is needed to clarify benefits, risks, and the appropriate duration of any restrictions.

Abstract: Background: Influenza causes substantial seasonal illness in children, particularly infants and young children. Children with chronic conditions, prematurity, neurologic disorders, or immunocompromise are at increased risk of complications. Although antiviral treatment complements vaccination and supportive care, pediatric evidence remains uneven: randomized trials have largely involved otherwise healthy outpatients, while evidence in hospitalized and medically complex children is mostly observational. Methods: This narrative review synthesizes evidence on the mechanisms, clinical use, and limitations of currently available influenza antivirals in children. It prioritizes pediatric trials, observational studies, and clinical guidance, with adult evidence considered where pediatric data are limited. Results: Oseltamivir remains the most widely recommended treatment, particularly for hospitalized children and those at increased risk. Its benefits in uncomplicated illness are generally modest, and vomiting is a recognized adverse effect. Zanamivir and peramivir are alternatives for selected patients, but their use is constrained by inhaled administration, airway disease, intravenous delivery, and limited evidence in severe illness. Baloxavir offers single-dose oral treatment and rapid suppression of viral replication; however, pediatric trials remain relatively small, reduced susceptibility can emerge during treatment, and evidence in severe disease is insufficient. Novel polymerase inhibitors and host-directed therapies remain investigational or have not established a clear clinical role in children. Conclusions: Future research should prioritize infants, children with comorbidities, and hospitalized patients, while addressing age-specific pharmacokinetics, antiviral resistance, and outcomes that matter to children and families.

Abstract: Background: Different modes of respiratory support may affect cardiovascular performance and systemic hemodynamics differently in neonates. Objective: The study aimed to evaluate the effects of invasive and non-invasive respiratory support on hemodynamic status and clinical outcomes in neonates. Methods: This prospective observational cohort study was conducted in the NICU. We enrolled 90 neonates and allocated them to three groups: invasive ventilation, non-invasive ventilation, and a control. Echocardiographic measurements were performed, including stroke volume (SV), cardiac output (CO), cardiac index (CI), mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (FAC), pulmonary artery systolic pressure (PASP), and myocardial performance indices for the left and right ventricles, as well as Doppler evaluation of the superior mesenteric and renal arteries. Assessments were conducted one hour after initiation of respiratory support and repeated after three days of ventilation. Results: After three days, invasive ventilation was associated with significantly lower SV, CO, CI, MAPSE, TAPSE, FAC, right ventricular SV, and pulmonary acceleration time, together with higher pulmonary artery systolic pressure compared with the non-invasive group (p=0.001, 0.001, 0.001, 0.002, 0.002, 0.006), respectively. The invasive group showed a significant reduction in Vmax values in the studied arteries. Neonates who developed acute kidney injury or died exhibited significantly impaired biventricular performance. Conclusions: Invasive mechanical ventilation is associated with lower cardiac output and evidence of greater impairment in both left and right ventricular functional indices over time, accompanied by higher rates of adverse clinical outcomes.

Abstract: Rotavirus-associated encephalopathy is a rare, severe complication in infants and young children, but its molecular basis remains unclear. Rotavirus nonstructural protein 4 (NSP4) is secreted from infected cells as a phospholipid-associated oligomer and can disrupt calcium homeostasis, yet its presence in circulation, interactions with the blood-brain barrier (BBB), and central nervous system access remain unproven. This hypothesis article integrates evidence on NSP4 structure and lipoprotein-like behavior, low-density lipoprotein receptor-related protein 1 (LRP1), caveolin-1, and developmental BBB transport. This article proposes that NSP4–lipid complexes could interact with glycosaminoglycans and, potentially, with LRP1- and caveolin-associated uptake in brain endothelial cells. If NSP4 crosses or is retained within the BBB, it might perturb calcium signaling and cellular homeostasis in endothelial and neural cells, including astrocytes, microglia, neurons, and oligodendrocyte precursor cells. These links are hypothesis-generating because NSP4–LRP1 binding, BBB transcytosis, and cell-specific effects in the developing brain remain unproven. This article outlines experiments to test or refute this developmental lipid-transport model.

Abstract: Primary hypertension (PH) in children is an increasingly prevalent multifactorial disorder involving complex interactions between genetic, metabolic, neurohormonal, immune, and environmental factors. Recent studies highlight the potential role of gut microbiota composition and immune dysregulation in the development and progression of PH and hypertension-mediated organ damage (HMOD) in children. The gut microbiota strongly influences immune responses and vascular function through its metabolites, such as short-chain fatty acids (SCFAs), which help maintain the intestinal barrier and modulate inflammation. Conversely, dysbiosis, defined as reduced microbial diversity and increased proinflammatory taxa, can exacerbate systemic inflammation and hypertension. Immune mechanisms, including T helper 17 (Th17) cell polarization and impaired regulatory T cell (Treg) function, facilitate sodium retention, endothelial dysfunction, and organ remodeling. This narrative review summarizes current knowledge of gut microbiota alterations and immunological pathways in pediatric PH, emphasizing the potential of inflammatory markers as early biomarkers. The review also discusses how lifestyle factors such as diet and physical activity modify the gut microbiota-immune axis and blood pressure regulation. Additionally, the study highlights gaps in current knowledge and possible directions for further research. Understanding these pathways offers promising opportunities for early diagnosis, risk stratification, and novel therapeutic interventions to prevent long-term cardiovascular complications in hypertensive children.

Abstract: The perinatal period has emerged as a critical window for the development of overweight and obesity and has therefore become a focus of scientific interest. According to the concept of developmental origins of health and disease (DOHaD), the first 1000 days after conception are of critical importance for the proper programming of stem cells. Multipotent mesenchymal stem cells (MSCs) have the capacity to differentiate into adipocytes both prenatally and postnatally. The aim of this review is to provide translational evidence for increased adipogenic programming of MSCs due to maternal obesity, cesarean delivery, and infant formula feeding. All three perinatal exposures plausibly converge on impaired canonical Wnt/β-catenin signaling in MSCs; this is directly supported for maternal obesity and indirectly for cesarean delivery and formula feeding through gut–endocrine mechanisms. Deficient Wnt/β-catenin signaling plays a pivotal role for the early committment of MSCs to the adipocyte lineage. These insights open up a comprehensive new approach to the understanding of the perinatal sequence of molecular events promoting early obesity development. Common medical practices during the perinatal period require reconsideration for the primary prevention of obesity.

Abstract: Introduction: Which of the two leading infectious killers of children—lower respiratory infections (LRIs) or diarrheal diseases—ends first should order child-survival investments, yet whether their transitions are symmetric is unknown. We compared the systems on a single counterfactual scale—a cross-system death-ratio series with formal uncertainty—at ages 0–19 years in the Global Burden of Disease Study (GBD) 2023. Methods: We extracted deaths and incident episodes, 1990–2023, from the GBD 2023 Results Tool, aggregating the under-5 band plus ages 5–9, 10–14 and 15–19. We computed cross-system death-ratio series, estimated annual percentage changes (EAPCs), pandemic-window changes with Monte Carlo uncertainty, an episode-fatality ratio proxy (EFR; deaths per 1,000 episodes, for 204 countries in 2023), and cross-system Escherichia coli trend correlations. Results: In 1990 the systems were indistinguishable (2.04 million LRI versus 2.00 million diarrhea deaths; ratio 0.98, 95% uncertainty interval 0.74–1.31). By 2023, LRI deaths (711,713) exceeded diarrhea deaths (379,958) 1.87-fold (ratio 0.53, 0.36–0.79; parity first excluded in 2013 and in every year thereafter except the 2020–2021 pandemic window). Improvement was age-synchronous for diarrhea but age-asymmetric for LRI (5–19-year EAPC −4.48% versus −1.74% per year). The pandemic window suppressed then released LRI deaths (year-on-year −18.4%, −9.0%, +12.8%, +8.1%; rebound in all five Socio-demographic Index quintiles) while diarrhea declined monotonically. Fatality gradients widened twice over: the 2023 LRI EFR was 49 times the diarrhea EFR; the low-to-high-SDI gradient steepened from 2.58 to 7.29 (LRI) and 6.40 to 22.50 (diarrhea); and country-level diarrhea EFRs tracked GDP per capita (ρ=−0.76) and LRI EFRs (ρ=0.85). E. coli mortality, coupled across systems until 2010 (ρ=1.000), decoupled thereafter (ρ=0.371): enteric deaths halved, respiratory deaths plateaued. Conclusion: The two systems share a starting point but no longer a trajectory. Pediatric infection frameworks should treat fatality, not incidence, as the binding constraint for LRI and extend case management and surveillance to the school-age children the transition has left behind.

Abstract: Aims Maternal infection during pregnancy is associated with offspring autism spectrum disorder (ASD) in individual-level studies (pooled OR 1.13–1.32; hospitalisation-grade 1.30–1.81), but negative-control and sibling designs attribute most of it to familial confounding (2.4 million Swedish children: pregnancy HR 1.16; pre-pregnancy control HR 1.25; sibling HR 0.94). Whether any country-level coupling exists has never been tested.Methods We conducted an ecological bounding analysis of the Global Burden of Disease Study 2023 (GBD 2023; 204 countries and territories, 1990–2023). Exposure: incident maternal sepsis and other maternal infections per 1,000 live births; outcome: ASD years-lived-with-disability (YLD) rate at ages 5–9 years. Distributed lags aligned exposure to birth cohorts (k=0–9; primary 7); country-and-year fixed effects and first differences were co-primary, with Driscoll–Kraay baseline inference and cluster- and bootstrap-robust variants. Bidirectional negative controls were judged by equivalence testing (TOST; δ=0.02 fixed before result inspection), future-exposure tests (t+3, t+5), and minimum-detectable-effect bounds.Results The within-country association was weakly negative (FE β=−0.0137; 95% CI −0.0234 to −0.0040 under Driscoll–Kraay; −0.0507 to +0.0233 under country clustering) and structurally non-causal: a flat lag profile with no birth-cohort peak at k≈7; future exposure associated at the same sign and two-thirds magnitude (−0.009/−0.008 at t+3/t+5); the main estimate sat below the negative-control background band's lower edge (band |β|≈0.02–0.05); and the association was zero where diagnostic capacity was high and stable (top HAQ tertile +0.0007), driven by middle-HAQ transition countries (−0.071). The conservative bound excludes positive elasticities above +0.023 (exposure doubling → +2.3% ASD YLDs); the individual-literature-implied elasticity (0.005–0.015) lies within it.Conclusions Country-level data bound but cannot adjudicate the maternal infection–autism question. Maternal sepsis reduction is justified by maternal and neonatal outcomes, not measurable ASD benefit, and GBD ASD maps should be read as diagnostic-capacity maps. Bidirectional negative controls with fixed equivalence margins and future-exposure tests offer a portable standard for reporting ecological nulls.

Abstract: Thalassaemias, sickle cell disease, and glucose-6-phosphate dehydrogenase (G6PD) deficiency share an evolutionary origin in malaria selection pressure, yet their pediatric trajectories may have diverged under unequal control programs. We jointly analyzed the 0–19-year burden of all three in the Global Burden of Disease Study (GBD) 2023. We extracted deaths, prevalence, and incidence (with 95% uncertainty intervals [UIs]) for the three causes from the GBD 2023 Results Tool—globally, by Socio-demographic Index (SDI) quintile and region—at seven key years (1990–2023), aggregated pediatric age bands into a 0–19-year total, computed key-year estimated annual percentage changes (EAPCs), and examined the 2019–2023 pandemic window. In 2023 the three diseases together caused 39,391 deaths (95% UI 24,456–54,325) at ages 0–19 years—equivalent to 45% of pediatric tuberculosis deaths—with sickle cell disorders contributing 74.6%. Their fates diverged: thalassaemia deaths fell 41.7% since 1990 (mortality-rate EAPC −2.11% per year), whereas sickle cell deaths rose 30.9% (EAPC +0.27%, non-significant). G6PD deficiency affected 168.7 million children (about one in 15) but caused only 1,554 deaths. Sub-Saharan Africa carried 91.8% of pediatric sickle cell deaths, and the low-versus-high-SDI mortality gradient was 66-fold for sickle cell disease versus 8-fold for the other two. The 2019–2023 pandemic window showed no global care-disruption signal. Three malaria-belt diseases met three fates—controlled, stagnating, and silently prevalent. Sickle cell disease, the largest pediatric killer of the three, has been left behind by the intervention architecture that succeeded against thalassaemias; closing the newborn-screening and hydroxyurea gap in sub-Saharan Africa is the defining equity task.

Abstract: Background: Asthma accounts for the great majority of the chronic respiratory disease burden below 25 years of age, yet pediatric analyses based on the Global Burden of Disease (GBD) 2021 round terminate in 2021, predating the full COVID-19 period. We estimated the global, regional, and national burden of asthma among individuals aged 0–24 years from 1990 to 2023. Methods: We extracted estimates from the GBD Results Tool, GBD Study 2023 (data downloaded 13–15 August 2026), and aggregated six measures (prevalence, incidence, deaths, disability-adjusted life-years [DALYs], years lived with disability, and years of life lost) across the 0–24-year age range—using the official under-5-years aggregate row (which includes the 1-year age group, for which no single-year estimates are published) plus the 5–9, 10–14, 15–19, and 20–24-year bands—for 204 countries and territories, 21 GBD regions, and five Socio-demographic Index (SDI) quintiles, with 95% uncertainty intervals (UIs). Trends were quantified as estimated annual percentage changes (EAPCs) for 1990–2023 and the 2019–2023 pandemic window. Results: In 2023, an estimated 150,837,112 (95% UI 103,730,853–218,576,263) individuals aged 0–24 years were living with asthma, with 22,126 (15,409–32,090) deaths and 7,753,206 (5,069,966–11,580,326) DALYs. Between 1990 and 2023, prevalent cases rose by 23.1% while the all-population age-standardized prevalence rate (ASPR) was stable (EAPC +0.01, 95% confidence interval −0.04 to +0.05) and the all-population age-standardized mortality rate (ASMR) declined (EAPC −1.56). During 2019–2023, the all-population ASPR increased significantly (EAPC +1.07, +0.63 to +1.52) and deaths increased by 3.78% in absolute counts (point estimate). Low-SDI countries concentrated 55.3% of asthma deaths at these ages, with an all-population ASMR 13.6 times that of high-SDI countries. The male-to-female ratio of deaths converged from 1.758 in 1990 to near parity (1.017) in 2023, with sex-specific UIs overlapping throughout. Ten countries accounted for 46.3% of global cases, led by the United States (12.90 million). Conclusions: Case numbers continue to grow while the all-population age-standardized prevalence rate remains flat, and mortality remains concentrated where health systems are weakest. Priorities include reliable inhaled-corticosteroid access in low-SDI settings, surveillance of adolescent girls and young women, and protection of chronic respiratory care continuity in pandemic preparedness.

Abstract: Objective To describe, for every country, pathogen-attributable fractions (PAFs) of childhood (0–19 years) lower respiratory infection (LRI) deaths in 2023, and to classify countries by etiologic composition for vaccine, treatment and hospital policy.Methods We analysed the Global Burden of Disease Study (GBD) 2023 etiology module: PAFs for 26 pathogens, 204 countries and four childhood age groups. Country PAFs for ages 0–19 years were computed as deaths-weighted averages. We derived a five-type typology by k-means clustering, quantified a hospital-associated pathogen group, and cross-tabulated profiles against pneumococcal conjugate vaccine (PCV) policy, death burden and age.Findings Streptococcus pneumoniae was the largest single contributor in all 204 countries (PAF 13.1%–51.5%; median 26.4%); nineteen countries exceeded 40%. Five composition types traced a gradient from pneumococcus hyper-dominance to diversified high-income profiles; Klebsiella pneumoniae ranked second in 125 countries and Staphylococcus aureus in 75. The hospital-associated group accounted for 19.1%–33.8% of deaths in every country (mean 27.6%), without high-income exemption. Intersecting PAF above 40% with the 20 highest-burden countries isolated Indonesia, Chad and, borderline, Somalia as priority cells (threshold-sensitive; Text S8); India, Nigeria and the Democratic Republic of the Congo formed the volume core. All 19 high-PAF countries completed nationwide PCV introduction only from 2021, or lacked a universal programme by end-2023.Conclusion One pathogen leads childhood LRI mortality everywhere, but with a four-fold gradient; country PAF profiles are a direct, reproducible input for prioritizing PCV completion, hospital-platform interventions and age-stratified strategies.

Abstract: Asthma accounts for the great majority of the chronic respiratory disease burden below 25 years of age, yet pediatric analyses based on the Global Burden of Disease (GBD) 2021 round terminate in 2021, predating the full COVID-19 period. We extracted estimates from the GBD Results Tool, GBD Study 2023, and aggregated six measures (prevalence, incidence, deaths, disability-adjusted life-years [DALYs], years lived with disability, and years of life lost) across ages 0–24 years for 204 countries and territories, 21 GBD regions, and five Socio-demographic Index (SDI) quintiles, with 95% uncertainty intervals (UIs); trends were quantified as estimated annual percentage changes (EAPCs). In 2023, an estimated 150,837,112 (95% UI 103,730,853–218,576,263) individuals aged 0–24 years were living with asthma, with 22,126 (15,409–32,090) deaths and 7,753,206 (5,069,966–11,580,326) DALYs. Between 1990 and 2023, prevalent cases rose by 23.1% while the age-standardized prevalence rate was stable (EAPC +0.01, 95% confidence interval −0.04 to +0.05) and mortality declined (EAPC −1.56); during 2019–2023, prevalence rose significantly (EAPC +1.07, +0.63 to +1.52) and deaths increased by 3.78%. Low-SDI countries concentrated 55.3% of asthma deaths at these ages; the male-to-female ratio of deaths converged from 1.758 (1990) to near parity (1.017; 2023). A country-level case-fatality proxy varied 1,446-fold across 178 countries, and reducing every country’s proxy to the best-quartile threshold would avert an estimated 91.0% of under-20 asthma deaths. Case numbers continue to grow while age-standardized prevalence remains flat, and mortality remains concentrated where health systems are weakest; priorities include inhaled-corticosteroid access in low-SDI settings, surveillance of adolescent girls and young women, and protection of chronic respiratory care continuity in pandemic preparedness.

Abstract: Background: Childhood and adolescent cancer mortality has declined for three decades, yet whether the COVID-19 pandemic interrupted this decline has never been quantified at the population level; the official Global Burden of Disease (GBD) 2023 childhood cancer analysis does not examine the 2019–2021 window. We analyzed the 0–19-year neoplasm burden in GBD 2023 with explicit attention to the pandemic window.Methods: We extracted deaths and incident cases for the GBD Level-2 cause “Neoplasms”—an envelope of malignant, benign and in-situ tumors—at ages 0–19 years, both sexes, 1990–2023, globally, for 21 regions and five Socio-demographic Index (SDI) quintiles. We computed crude rates on back-calculated populations, long-term estimated annual percentage changes (EAPCs), and pandemic-window changes with Monte Carlo-propagated uncertainty intervals (UIs); a mortality-to-incidence (M/I) ratio served as a comparative detection-and-survival proxy. Same-pipeline pediatric tuberculosis and lower respiratory infection series provided internal controls. Because approximately 96% of incident cases are benign or in-situ tumors, incidence-side and M/I absolute values are interpreted comparatively only; all primary inference is mortality-based.Results: In 2023, neoplasms caused 148,436 deaths (95% UI 139,201–157,671) at ages 0–19 years, 26.6% fewer than in 1990—versus 144,000 (131,000–162,000) in the official malignant-only analysis, whose intervals fully overlap ours. Reversing three decades of decline, deaths rose 4.7% (−3.3 to +13.5) between 2019 and 2021 to 152,553, the highest since 2008; the rise was broadly graded by development (high-SDI −2.1% to low-SDI +7.9%) and had not fully receded by 2023. Mortality declined slowest among comparator diseases (EAPC −1.61 versus tuberculosis −3.96 and lower respiratory infections −3.89); the neoplasm-to-tuberculosis death ratio crossed over from 0.78 to 1.69. The low-to-high-SDI M/I gap widened from 14.5-fold to 21.7-fold. Adolescents aged 15–19 years became the largest mortality band among ages 5–19 years—nearly level with the under-5 band (41,182 versus 42,222 deaths)—and rose most of any band over 2019–2023 (+8.0%), while under-5 deaths fell 6.3%. Interrupted time series analysis formally confirmed the mortality reversal: at the BIC-optimal intervention year of 2019, the global mortality series showed an immediate level increase of 7.5% (95% CI 2.4 to 12.9), with 2023 mortality 15.8% (10.7 to 21.2) above the counterfactual pre-pandemic trend.Interpretation: The pandemic window marks a fault line in pediatric cancer control: a development-graded mortality reversal superimposed on a widening survival divide. Because GBD 2023 mortality models incorporate pandemic-period covariates, we present this as a data-and-model signal requiring triangulation, not a pure causal claim. Reaching the WHO childhood cancer survival targets requires closing the diagnostic-treatment gap the pandemic exposed.

Abstract: Purpose: To present a case of mirtazapine associated seizures in an adolescent boy and to conduct a systematic review of published cases of seizures occurring in association with mirtazapine use. Methods: We presented our case and conducted a systematic search, following the PRISMA Statement, in the PubMed and Scopus databases for mirtazapine associated seizure cases, until 12th September 2026. Results: A 15-year-old patient arrived at the emergency department of our hospital via ambulance due to a generalized tonic-clonic seizure occurring 15 minutes prior. The toxicology report of his urine sample was positive for mirtazapine metabolites. He was self-administering mirtazapine for an unknown amount of time. This was the most likely cause of the generalized tonic-clonic seizures. No further seizures occurred during hospitalization. Our systematic search yielded 7 published cases. The median age was 50 years. The dosage of mirtazapine ranged from 7.5 mg to 60 mg per day. Excluding one case with an overdose, seizures presented a few days after mirtazapine initiation or dosage escalation—three cases presented with focal seizures and 3 cases with generalized seizures. Two cases had a positive history of epilepsy, and 4 cases were on other medications that can lower the seizure threshold. In most cases, withdrawal of mirtazapine was sufficient for seizure resolution. Conclusion: The available evidence cannot establish a causative relationship between mirtazapine and seizures. The temporal association observed in several cases suggests that physicians should remain vigilant for seizure occurrence, particularly in individuals with pre-existing epilepsy or other potential seizure risk factors.