Children

Abstract Importance Acute otitis media is the most common infection in children and a major reason for antibiotic prescriptions, up to one third of which may be unnecessary. Sector of care may influence AOM management through differences in access to care, specialist involvement, parental expectations and financial foundation. Objective The objective is to examine differences in antibiotic prescribing practices between healthcare sectors. Design This is a nationwide register-based study comparing data from different healthcare sectors. Setting Finnish primary and secondary healthcare, covering both public- and private-sector visits. Prescriptions and sociodemographic information were linked from nationwide registers. Participants We included children under 18 years old who received a diagnosis of acute otitis media, defined by ICD-10 codes H65-H67, between January 1, 2017 and December 31, 2022. Exposures The exposure is the sector of care (public sector vs. private sector). Main Outcomes and Measures Primary outcomes were antibiotic prescribing, guideline adherence of the prescribed antibiotics, and rates of management failure. Secondary outcomes included antibiotic selection and guideline-adherent eligibility for tympanostomy tube placement. Associations were estimated using adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results The study included 295 064 children with 596 634 acute otitis media index visits, of which 77.6% resulted in an antibiotic prescription. Private-sector visits were associated with higher odds of antibiotic being prescribed (adjusted odds ratio [aOR]: 1.45; 95% CI: 1.41-1.49). Overall, 87.3% of antibiotic prescriptions were guideline adherent, but private-sector care was associated with lower odds of guideline-adherent prescribing (aOR: 0.64; 95% CI: 0.60-0.69). Compared with amoxicillin, the private sector showed higher odds of prescribing amoxicillin-clavulanic acid (32.8% vs. 8.3%; aOR: 3.00; 95% CI: 2.91-3.10). Management failure occurred in 7.0% of episodes and was more common in the private sector (aOR:1.52; 95% CI: 1.48-1.56). Only 48.7% of all tympanostomy tube insertions met the eligibility criteria. Conclusions and Relevance In this study overall adherence to guideline-recommended antibiotic treatment for AOM was high in Finland. Nevertheless, observed clinically meaningful sectoral differences in antibiotic selection, treatment failure, and tympanostomy eligibility adherence indicate a need for targeted antimicrobial stewardship and quality-improvement efforts, especially in the private sector.

Introduction Language functional MRI (fMRI) is a valuable tool for presurgical planning in epilepsy. Functional MRI can be challenging in children, and head motion can compromise its utility. The candidacy of patients with ADHD for fMRI is sometimes queried regarding concerns about possible head motion. In 2020, we implemented an fMRI task training program, via telehealth and/or mock MRI. We aimed to determine whether training increased language lateralisation success and/or reduced head motion in all patients, and in those with ADHD. We also aimed to determine whether patients with ADHD exhibited more head motion during fMRI than those without ADHD. Methods We retrospectively identified 223 epilepsy (85%) and other neurosurgery patients, (241 scans including repeats) with language fMRI at Royal Children's Hospital, Melbourne, Australia, 2016-2024. There were 24 individuals with ADHD listed in the Electronic Medical Record, five of whom had diagnoses of both ADHD and autism; and nine with autism. Language lateralisation success was determined by clinician description recorded as left/right/bilateral in the medical record. 99 patients were provided the training including fMRI task practise. Head motion was quantified by maximum Framewise Displacement (FDmax; mm). Results ADHD was associated with lower language lateralisation success. Training was associated with greater language lateralisation success, across all patients, and in those with ADHD. Regarding ADHD and head motion, outliers in FDmax were seen in 5 young patients with ADHD. Data were trimmed to allow separate investigation of FDmax for the sample with and without extremes of head motion. In untrimmed data, FDmax was significantly higher in patients with ADHD than in those without. In trimmed data, FDmax was on average lower in patients with ADHD than those without, however this was not statistically supported. Regarding training and head motion, across all patients, FDmax was significantly lower for scans with training than without. In patients with ADHD, FDmax was on average lower for scans with training, however training was not associated with FDmax. Conclusions Language fMRI training was associated with higher language lateralization success, particularly in patients with ADHD. Training was associated with reduced head motion across all patients. Although some young patients with ADHD had substantial head motion, most in our sample did not move more than those without ADHD. We conclude that the training program increases success of language fMRI, and that an ADHD diagnosis should not be a contraindication to language fMRI.

Background Advancements in medical imaging have enabled non-invasive diagnosis and staging of cystic fibrosis (CF) using CT scans, revealing dilated airways, an increased number of visible airways, and airway generation splits in these patients. However, manual characterization of airways remains time-consuming and challenging due to the numerous structural changes, thereby limiting clinical feasibility. This study aims to develop an automated algorithm to characterize airways from segmented lung CT scans and apply this to a retrospective population. This approach reduces the time required to analyze images and obtain disease-staging results. Methods This framework consists of two stages. The first stage extracts and skeletonizes the airway tree from lung CTs, while the second stage measures lung features, including airway volumes, branch counts, generation splits, diameters, and cross-sectional areas. This permits comprehensive characterization for use in clinical assessment. Results The airways analysis was performed on 169 CT volumes ranging in age from 6 to 18 years of age, revealing substantial differences in detected airway branches, generation splits, and normalized airway volume between the control and CF groups. The framework also measures airway diameters and cross-sectional areas, revealing an increase in the number of small airways in cystic fibrosis patients, due to early bronchiectasis. These findings align with previous research and demonstrate the framework's ability to accurately quantify airway changes in patients with CF. Discussion The framework extracts entire airway trees, facilitating measurements of volume, branch count, diameters, and cross-sectional areas, which change with CF severity and/or treatment. However, partial lung atelectasis can limit the accuracy of airway detection in moderate-to-severe cases. Funding NIA U54 AG054345 and NIA R21 AG07857501

This cross-sectional study evaluated the association of tooth loss and oral health-related quality of life (OHRQoL) with sexual function in adult women attending a primary dental care service. Methodology: Ninety-nine sexually active women aged 19-66 years were consecutively recruited from a primary dental care service between January and October 2023. Tooth loss was quantified by standardized oral examination. OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14), and sexual function was assessed using the Female Sexual Function Index (FSFI). Sexual dysfunction was defined as FSFI <=26.5. Spearman rank correlation was used for bivariate analyses. Multivariable logistic regression was used to evaluate factors associated with sexual dysfunction, including number of missing teeth, OHIP-14 score, age, and relationship status. Results: Tooth loss was present in 83.8% of participants, with a median of 4 missing teeth (interquartile range [IQR], 1-10). Sexual dysfunction was identified in 62.6% of women. FSFI scores were negatively correlated with number of missing teeth (rho = -0.407; p < 0.001), OHIP-14 score (rho = -0.279; p = 0.005), and age (rho = -0.334; p < 0.001). In multivariable logistic regression, OHIP-14 score was independently associated with sexual dysfunction (OR = 1.05; 95% CI, 1.01-1.10; p = 0.015), whereas number of missing teeth was not independently associated after adjustment. Conclusion: Worse OHRQoL was independently associated with sexual dysfunction, whereas tooth loss was associated with lower FSFI scores only in bivariate analysis. These findings are compatible with the hypothesis that the impact of tooth loss on sexual function may be partly explained by oral health-related quality of life, but longitudinal studies are required to test causal and mediational pathways. Keywords: tooth loss; oral health; quality of life; sexual dysfunction, physiological; women; cross-sectional studies

Background Alveolar bone assessment in periodontal practice relies on radiography and clinical probing, both of which have well-documented limitations in precision. Intraoral high-frequency ultrasonography (US) offers a radiation-free alternative with potential for sub-millimeter resolution, the validity and precision for detecting minute osseous changes have not been established. The purpose of this study was to evaluate the concurrent validity and measurement precision of intraoral US for detecting alveolar bone-level changes in patients undergoing crown lengthening and osseous surgery, thereby enabling its translation to monitor osseous changes in patients with periodontitis. Methods Ten patients (28 tooth sites) undergoing crown lengthening or osseous surgery at a USC Advanced Grad Perio clinic were enrolled in this prospective observational study. Distance from the cementoenamel junction (CEJ) to the Alveolar bone crest (ABC) was measured at pre- and post-operative time points using a 40 MHz handheld intraoral US transducer and, intraoperatively, by standardized clinical photography. Agreement was assessed by Pearson correlation and Bland-Altman analysis. Measurement precision was quantified using the standard error of measurement (SEM) and minimum detectable change (MDC). Results Preoperative agreement between methods was excellent (r = 0.977; Bland-Altman bias = -0.009 mm; 95% limits of agreement [LoA]: +-0.40 mm). Post-operative correlation remained strong (r = 0.912; bias = 0.123 mm; LoA: -0.85 to +1.10 mm). Both methods detected statistically significant post-surgical increases in the ABC-to-CEJ distance (p < 0.001), as anticipated. US demonstrated substantially superior precision: preoperative SEM 0.058 mm with US versus 0.128 mm clinically, yielding MDC values of 0.160 mm (US) versus 0.354 mm (clinical), providing a 2.2-fold precision advantage. Conclusions Intraoral US demonstrated strong concurrent validity with clinical photography and a reproducible precision advantage in detecting alveolar bone-level changes in patients with periodontitis. These findings support its clinical utility as a radiation-free, high-sensitivity bone monitoring tool. Larger longitudinal studies with CBCT validation are warranted.

Background: Accurately identifying patients who will require opioids after third molar extraction could improve pain management while supporting opioid stewardship. This study evaluated surgeon accuracy in predicting supplemental opioid use following treatment with ibuprofen and acetaminophen. Methods: Patients (N=85) undergoing third molar extraction were treated with a standardized analgesic regimen of ibuprofen+acetaminophen, with supplemental opioid if needed. Four surgeons independently reviewed preoperative radiographs, assessed surgical difficulty using the Pederson scale, and rated the likelihood of supplemental opioid use on a 5-point Likert scale. Inter-rater reliability was assessed using intraclass correlation coefficients (ICC). The relationship between surgeon ratings and postoperative opioid use was evaluated using logistic regression and receiver operating characteristic (ROC) analysis. Results: Seventeen patients used supplemental opioid analgesics. Inter-rater reliability among surgeons was moderate (ICC3=0.606, 95%CI: 0.505-0.700), while reliability of the average rating across surgeons was good (ICC3k = 0.860, 95% CI: 0.804-0.903). Median surgeon rating was not associated with postoperative opioid use (OR: 0.800, 95% CI: 0.414-1.51, p=0.496) and demonstrated poor discrimination (AUC: 0.551, 95% CI: 0.392-0.710). Surgeon ratings were positively associated with Pederson score (beta=0.073, 95%CI: 0.050-0.096; p<0.001). Conclusions: Surgeons demonstrated moderate agreement, but these assessments did not accurately identify patients who ultimately required supplemental opioids. Surgeon judgments appeared to be influenced by anticipated surgical difficulty. Practical Implications: Clinicians should follow current recommendations against routine "just-in-case" opioid prescribing after third molar extraction. Future studies should focus on identifying clinical and biological predictors of inadequate analgesic response to NSAIDs to support individualized pain management strategies.

Relapse of aligned mandibular anterior teeth and the progressive collapse of the mandibular anterior arch are historically striking problems for orthodontists. The etiology of this collapse, and the cause of mesial molar drift, are unknown. However, light continuous (quasi-continuous) intra-oral pressures and forces applied to the mandibular dentition have been implicated. To explore this further, we use three-dimensional finite element analysis to investigate the influence of these intra-oral loads (tongue pressure, lip-cheek pressure, and interdental force) on mandibular arch collapse and mesial molar drift. Dentitions of three-dimensional finite element mandibular models were subjected to a wide range of simulated tongue pressures, lip-cheek pressures, and transseptal fiber-mediated interdental forces reported in the literature. Resulting crown displacement measurements from these isolated loads were made along with measurements resulting from simultaneous combined application of literature-defined mean tongue pressure, lip-cheek pressure, and interdental force. Our results indicate that tongue pressure alone results in generalized arch expansion and tooth spacing while lip-cheek pressure and interdental force result in generalized arch collapse, anterior crowding, and mesial molar displacement. Simultaneous application of tongue pressure, lip-cheek pressure, and interdental force mean values, as would occur in vivo, results in incisor crowding, intercanine width reduction, and mesial molar displacement. Our results suggest mandibular anterior arch collapse (incisor crowding / intercanine width reduction), and mesial molar displacement result from simultaneous application of tongue pressure, lip-cheek pressure, and interdental force.

Background/Objectives Dental anxiety remains a significant psychological barrier to oral healthcare, particularly for invasive surgical procedures such as tooth extraction. Aromatherapy using Lavandula angustifolia (lavender) has been proposed as a non-pharmacological adjunct to manage acute preoperative anxiety. This clinical trial evaluated the efficacy of inhaled lavender essential oil on anxiety severity in patients awaiting elective single-tooth extraction. Methods An assessor-blinded randomized controlled clinical trial with limited participant blinding (inherent to the recognizable scent of the intervention), registered with the Iranian Registry of Clinical Trials (IRCT20190920044824N1), was conducted among 60 patients requiring non-surgical tooth extraction. Participants were randomly assigned to an intervention group (n=30), receiving two drops of pure lavender essential oil on a sterile gauze for 20 minutes of inhalation, or a control group (n=30), receiving sweet almond oil as an olfactory placebo. The primary outcome was the severity of somatic anxiety symptoms, measured pre- and post-intervention using the Beck Anxiety Inventory (BAI). Because a significant baseline-by-treatment interaction was detected, a General Linear Model (GLM) retaining this interaction term was used to estimate adjusted group means at the grand-mean baseline, with bootstrap 95% confidence intervals (10,000 resamples). Two pre-specified checks of robustness were performed: (i) an unadjusted, baseline-naive Mann-Whitney U comparison of raw post-intervention scores, and (ii) a sensitivity analysis re-fitting the adjusted model after excluding two baseline outliers identified by inspection of model residuals. Results There were no significant baseline differences between the intervention and control groups regarding sex distribution (p=0.100), mean age (p=0.479), or pre-intervention BAI scores (Mann-Whitney p=0.215). A significant baseline-by-treatment interaction was detected (p<0.001). In the full sample (n=60), the baseline-adjusted GLM estimated a lower post-intervention BAI mean in the intervention group (22.38) than the control group (23.09), an adjusted difference of -0.71 (bootstrap 95% CI: -1.41 to -0.06; p=0.028). However, this signal was not robust: after excluding two patients identified as outliers in the model residuals (n=58), the adjusted difference attenuated to -0.51 and was no longer statistically significant (bootstrap 95% CI: -1.11 to 0.10; p=0.098). The unadjusted comparison of raw post-intervention scores was likewise not significant in the full sample (Mann-Whitney p=0.754). Conclusions A baseline-adjusted analysis of this trial produced an initial signal suggesting a small anxiolytic effect of inhaled lavender, but this signal was not stable under a pre-specified outlier-exclusion sensitivity analysis and was not supported by the unadjusted comparison of raw scores. Taken together, the totality of evidence from this trial is insufficient to conclude that inhaled lavender aromatherapy produces a reliable reduction in acute preoperative dental anxiety. Beyond its clinical findings, this trial offers a concrete, quantified illustration of how baseline imbalance and a small number of influential observations can generate a fragile, model-dependent treatment signal in a modestly sized randomized trial, a methodological caution directly relevant to the design and analysis of future small RCTs in dental and complementary medicine research.

Background: Automatic tube compensation (ATC) was designed to compensate for the additional resistive load imposed by the endotracheal tube during spontaneous breathing. In ATC mode, the ventilator adds or subtracts the flow-dependent pressure drop across the tube during both inspiration and expiration so that tracheal pressure remains close to PEEP. Early prototype ventilators achieved true tracheal-pressure control and showed physiological and clinical benefits, but clinical studies with commercial systems have failed to confirm these earlier findings. A 2003 bench study found that commercial ventilators provided, at best, only partial tube compensation, unlikely to result in meaningful clinical benefit. We therefore tested whether this limitation has been remedied in contemporary ICU ventilators. Methods: We performed a bench comparison of five commercial ICU ventilators and an ATC prototype ventilator designed to accurately compensate for the flow-dependent resistance over a wide range of flow rates. An active lung simulator generated spontaneous breathing patterns with weak, moderate, and strong inspiratory efforts at different PEEP levels. We tested each breathing pattern through endotracheal tubes with inner diameters of 7 and 8 mm, and measured airway pressure, tracheal pressure, and flow during CPAP with and without ATC. Breathing through the tube against open atmosphere served as a zero-PEEP/T-piece reference. Results: In CPAP mode, the commercial ventilators showed flow-dependent airway-pressure deviations, amounting to a substantial added resistance of 1.5 - 6.5 mbar/(L/s), whereas the ATC prototype ventilator imposed an added resistance of only 0.6 mbar/(L/s). In ATC mode, the commercial ventilators reduced the resistive load by no more than by 25%, and large tracheal-pressure deviations remained, especially at higher inspiratory effort and during expiration. In some cases, the residual load during ATC was even greater than the load during unsupported breathing through the tube. By contrast, the ATC prototype ventilator maintained tracheal pressure close to PEEP throughout the breathing cycle and eliminated on average 79% of the tube-related resistive load. Conclusions: In the commercial ventilators evaluated in this study, the defining physiological objective of ATC was only partially achieved. Therefore, clinical benefits previously reported for tracheal-pressure control support should be interpreted with caution when applied to commercial ATC implementations, unless effective tube compensation has been demonstrated under relevant conditions. These findings suggest that more advanced control approaches, such as those implemented in the ATC prototype ventilator, may be required to achieve consistent and physiologically accurate tube compensation.

Objective: Breast milk is the optimal source of nutrition for preterm infants, however, low breast milk production is common following a preterm birth. This study aimed to determine if taking brewers yeast' or beta-glucan improves daily expressed breast milk volume. Design: Randomised, blinded, parallel, placebo-controlled trial. Setting: Three Australian tertiary level neonatal units. Patients: Mothers with a singleton or twin pregnancy who gave birth at less than 34 weeks' gestation. Interventions: Mothers were randomised within 72 hours of birth into three parallel groups in 1:1:1 ratio to receive either brewers' yeast, beta-glucan or placebo capsules for seven days. Main outcome measure: Total expressed breast milk volume over a 24-hour period on day seven of intervention. Results: A total of 105 mothers underwent randomisation between August 2022 and April 2024 (36 brewers' yeast, 35 beta-glucan, and 34 placebo). The adjusted mean difference in daily expressed breast milk volume was 94 mL/day (95% CI -51 to 239 mL/day) between the brewers' yeast and placebo groups, and -25 mL/day (95% CI -173 to 123 mL/day) between the beta-glucan and placebo groups. Maternal side effects were similar across groups. Conclusion: We found no clear effect of short-term administration of brewers' yeast or beta-glucan on breast-milk production following preterm birth; both interventions were well tolerated. Given the small sample size, these findings do not rule out the possibility of a clinically meaningful benefit of brewers' yeast and suggest further research with a larger sample size may be warranted to clarify the potential clinical impact. Trial registration number ACTRN12622000968774.

Background Diarrheal disease remains a major public health concern among under-five children, particularly in the displaced population, where sanitation, water supply, and health care access are limited. Although it is a 3rd leading cause of under-five morbidity and mortality, limited data exist on the prevalence and determinants of diarrhea in IDP centers. Objective To assess the prevalence and associated factors of diarrhea among under-five children in Debre Birhan City Internally Displaced People's centers in 2025. Methods A cross-sectional study was conducted from December 16--30, 2025, in Debre Berhan citys internally displaced people centers. A total of 355 mothers/caregivers were selected using systematic random sampling. Data were collected through face-to-face interviews using structured, pre-tested questionnaires via the Kobo Collect application. The data were analyzed by using SPSS version 26. Bivariable and multivariable logistic regression were fitted to identify factors associated with the outcome variable. An adjusted odds ratio with its 95% CI was used to determine the strength of association, and variables with a p-value of <0.05 were considered significant. Result The prevalence of diarrhea among children under five years in Debre Berehan city internally displaced peoples center was 32.4% (95% CI: 28-37). Three factors, unable to read and write educational status of mothers (AOR =3.1; CI: 1.27-7.6), open dumping waste disposal method (AOR=2.63, 95%CI: 1.27-5.5), unvaccination (AOR=3.9, 95%CI: 1.4-10.85) and partial vaccination (AOR= 2.22, 95%CI: 1.25-3.95) were significantly associated with the outcome variable diarrhea. Conclusion The prevalence of diarrhea among children under five in the IDP center of Debre Berhan city was high. Management strategies to improve maternal health literacy, promote proper waste management and sanitation, and enhance outreach immunization services are crucial for reducing the burden of diarrhea.

Introduction: Early childhood vision screening is critical for detecting amblyopia and other vision-threatening conditions. Despite screening recommendations during well-child visits, rates remain low. Red reflex assessment is recommended to identify serious ocular pathology, yet its use in primary care is not well described. We examined rates and drivers of vision screening in pediatric primary care. Methods: We conducted a retrospective review of electronic health records for children 3 to 5 years attending well-child visits in 2022 in one of three representative primary care clinics within a university health system. Outcomes were documented red reflex and functional vision tests. We evaluated associations with patient demographics and clinic site using multivariable logistic regression Results: Among 1,003 visits, 21.1% (n=212) had a documented red reflex assessment, and 60.8% (n=610) a functional vision test. Younger children (ages 3 and 4 vs. 5 years) had higher odds of red reflex assessment [adjusted odds ratio (aOR) 9.00 and 8.64], and lower odds of a functional vision (aOR 0.47 and 0.59) test. Females had higher odds of red reflex assessment (aOR 1.53). Other/Multiracial children had lower odds of red reflex assessment than Non-Hispanic White children (aOR 0.48). Screening rates varied significantly by clinic site Conclusions: Visual function and red reflex assessment are inconsistently performed in pediatric primary care, with particularly low rates of red reflex documentation. Screening rates varied between clinics and were affected by age. These findings highlight missed opportunities for early detection of vision-threatening conditions and identify targets for improving adherence to pediatric vision screening recommendations

There were substantial changes in NIH policies regarding research funding in FY2025. This work examines NIH funding for pediatric research FY2020 through Q2FY2026 including the number and cost of awards, the number of first year (type 1) awards, the number of Notices of Funding Opportunity, and the topical focus of research awards. NIH funding for pediatric research declined >20% in the first two quarters FY2025-FY2026 with proportionally greater reductions in first year awards and Notices of Funding Opportunity. Changes were also noted in the topic prevalence of new awards consistent with 2025 guidelines identifying topics "not aligned with NIH priorities." These results suggest that pediatric research aimed at advancing healthcare for children is at risk with potential collateral consequences beyond childhood.

Background Minimal intervention dentistry (MID) is promoted as a prevention-oriented approach to caries management, but its integration into routine practice remains uneven. Existing research often examines MID-related knowledge, attitudes, or practices separately, offering limited insight into how these dimensions co-occur within individuals or are conditionally associated. Methods This exploratory cross-sectional survey examined multidimensional MID uptake among 327 Romanian dental students, residents, and specialists from five university centers. Ten MID-related scores were analyzed, including nine formative composites and one single-item peer-norm indicator. K-means clustering examined uptake profiles, and Gaussian graphical model network analysis with stepwise BIC selection examined conditional associations among constructs. Results A two-cluster solution was highly reproducible but modestly separated (n = 144 vs n = 183; average silhouette width = 0.13; mean Jaccard similarities = 0.92 and 0.94). The profiles reflected broadly lower versus higher uptake across knowledge-, belief-, and practice-related dimensions, while perceived peer norms for hygiene instruction showed the opposite pattern. Profile membership was not clearly patterned by gender, age band, professional status, or clinical experience. The primary network included 14 non-zero edges out of 36 possible edges, all positive; the strongest partial association linked diagnostic knowledge to diagnostic methods used in practice (partial r = .22). Familiarity, diagnostic knowledge, and general practices occupied more interconnected positions descriptively, but limited centrality stability precluded interpreting them as intervention targets. Conclusions MID uptake in this sample was better represented as a continuum of modestly differentiated profiles than as sharply separated participant types. The findings provide an exploratory map of multidimensional MID uptake and may inform future survey validation, implementation research, and dental education studies. Because the study was cross-sectional, convenience-sampled, and based on self-report, findings should be interpreted as hypothesis-generating rather than causal or population-representative.

Orofacial clefts (OFCs), including cleft lip (CL), cleft palate (CP), and cleft lip with cleft palate (CLP), are among the most common craniofacial malformations in humans, with a birth prevalence of approximately 1 in 1,000 live births globally. Non-syndromic forms of OFC are predominantly genetic, with significant variability in prevalence across populations. Understanding the genetic underpinnings of OFCs remains a key public health priority, given the substantial medical and societal burden of these conditions. Recent genome-wide association studies (GWAS) have implicated numerous genetic loci, but challenges remain due to genetic heterogeneity and complex gene-environment interactions. This study aimed to identify sex-specific genetic risk factors for cleft lip with or without cleft palate (CL/P) through a meta-analysis of whole genome sequencing (WGS) data from 1,922 case-parent trios across eight diverse cohorts. Our approach revealed four SNPs in three distinct regions that showed genome-wide significant sex-specific effects. However, despite each of these SNPs passing standard quality control filters, follow-up analyses showed that these signals most likely were technical artifacts caused by sequencing errors, in particular mis-mapped reads due to sequence similarities with the sex chromosomes. These findings highlight the necessity for careful scrutiny when studying differences between the sexes in genetic association studies.

Background: The hydrodynamic model of hydrocephalus proposes that ventriculomegaly is driven by exaggerated intraventricular pulsations rather than impaired CSF circulation alone. Under this model, endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) treats hydrocephalus by creating a pulsation absorber and by reducing a primary source of intraventricular pulsation. However, direct intraoperative human evidence supporting this two-step mechanism is lacking. This study aimed to test the hypothesis that ETV followed by CPC would produce measurable, stepwise decreases in mean intraventricular pressure (ICP) and pulsation amplitude in infants with hydrocephalus. Methods: This single-institution proof-of-concept study included infants with symptomatic hydrocephalus undergoing ETV/CPC as the first definitive treatment. A fiber-optic ICP sensor was attached to the operative ventriculoscope and passively recorded mean and pulsatile ICP (pulsation amplitude) throughout the procedure. Longitudinal brain parenchymal volume (BPV) and cerebrospinal fluid volume (CSFV) were obtained through segmentation of clinically acquired T2-weighted MRI and converted to age- and sex-matched z-scores. All patients were followed for a minimum of 6 months postoperatively. Results: Five infants (median corrected age at ETV/CPC 8 months) were included. No surgical complications occurred, and no ETV/CPC failures were observed during follow-up. Overall, mean ICP decreased by 56-97% after the combined procedure in four patients. In three patients (Patients 1, 3, and 5), both mean ICP and pulsation amplitude decreased stepwise following ETV and then CPC, consistent with the hypothesized therapeutic mechanism. Patient 4 demonstrated a large reduction in mean ICP after ETV with minimal additional effect from CPC and no significant change in pulsation amplitude. Patient 2 demonstrated neither a reduction in mean ICP nor a meaningful change in pulsation amplitude after either procedure; this patient also had a delayed and atypical clinical response. Intracranial segmentation demonstrated BPV z-score stabilization within normal range and CSFV plateau in all patients after surgery. Conclusions: This proof-of-concept study provides the first direct intraoperative human evidence supporting the hydrodynamic mechanism of ETV/CPC in a subset of infant with hydrocephalus. Our findings suggest that determination of intraoperative ICP parameters is feasible, safe and might ultimately prove helpful in improving patient selection for ETV/CPC, warranting further investigation in larger cohorts.

Objective: This study aims to identify which markers of tissue hypoperfusion - specifically lactate levels, central venous oxygen saturation (ScvO2), and venous arterial carbon dioxide gradient (CO2 gradient) - have the highest sensitivity and specificity in predicting the discharge of postoperative cardiac surgical patients from the ICU within 48 hours. This is an exploratory, hypothesis-generating investigation. Methods: Prospective observational study involving 100 patients in the Surgical ICU at InCor-HCFMUSP undergoing cardiac surgery with cardiopulmonary bypass. Perfusion markers were assessed at ICU admission and 24 hours post-admission. Results: ScvO2 at 24 hours was the only marker significantly associated with ICU discharge (OR=1.096; 95% CI=1.020-1.180; p=0.012). Formal DeLong's test confirmed ScvO2 had significantly superior discriminatory performance compared to lactate (AUC 0.661 vs. 0.428; p=0.004). Lactato and CO2 gap showed no significant associations. Conclusions: In this exploratory cohort, ScvO2 at 24 hours post-admission showed a statistically significant association with early ICU discharge and superior discriminatory performance compared to lactate. These findings are hypothesis-generating and require prospective validation before clinical recommendations can be made.

Rationale: Infections due to Extended-spectrum {beta}-lactamases-producing Enterobacterales (ESBL-PE) require empirical treatment with carbapenems. ESBL-PE carriage is considered as a risk factor for ESBL-PE involvement during ICU infection. Our aim was to determine factors that may predict the actual involvement of ESBL-PE. Methods: A two-periods bicentric ambispective study including ICU ESBL-PE carriers patients from April 2011 to January 2019. All ESBL-PE carriers who developed an infection were analyzed. Results: 6112 patients and 4902 patients were screened during the two periods. 384 and 232 ESBL-PE carriers were identified. Total number of infectious episodes were 146 and 114, respectively. A total of 144 pneumonias, 42 urinary tract infection and 45 digestive infections were studied. An ESBL-PE was involved in 35 (24.3%) episodes of pneumonia, and 44 (37.9%) of extra-pulmonary infections. The most frequent ESBL-PE involved were K. pneumoniae, E. cloacae and E. coli. Similar species and phenotypes were present in colonisation and infection in 29 (82.8%) of pneumonia and in 40 (90.9%) of extra-respiratory infection. Multivariate analysis identified Klebsiella pneumonia or Enterobacter cloacae carriage as risk factor for ESBL-PE involvement in pneumonia and E. coli carriage and detection of ESBL-PE carriage before ICU admission as protective factors. Conclusion: In our study an ESBL-PE involvement is infrequent in pneumonia. A known carriage before ICU admission and E. coli carriage are factors associated with the absence of ESBL-PE un the episode of respiratory infection. A confirmation of our findings could lead to a reduction in the empirical use of carbapenems in this population.

Background: Early relational health (ERH) constructs are derived fromresearch observations rather than lived experiences. This study foregrounds diverse parent voices to examine how they describeconnectionwith their young children. Methods: Usingcommunity-based participatory research (CBPR),this study was co-designed withparent leadersfromReach Out and Read. A semi-structured interview guidewas co-designed,and parent leaderssubsequentlyconducted and transcribed 18 interviews with parents from their networks.Researchersanalyzed transcripts using Reflexive Thematic Analysis.Member checking sessions with parent leadersinformedthe analytic framework. Results:Sixorganizing principleswereidentified.(1) Parent-child connection begins with an instinctual sense of responsibility.(2)Connectionebbs and flows as parent and child adapt to one another through dailyactivities.(3) Family circumstances, including family structure, cultural expectations, and intergenerational values, directly shape this connection. (4) Parents' own upbringings and past relationships indirectly shape how they connect with their child. (5) Forconnectionto grow, parents must show up physically and emotionally for their children despite competing demands. (6) Parentsgrow through engaged parenting, and that growth feeds back into the connection, creating a self-sustaining cycle of relational health.Conclusions:Our analysis generated twoconstructs underspecified in ERH frameworks.Parents described their sense of responsibility as immediate and instinctual, preceding an emotional bond.Parentsdemonstratedtheir agency in deciding what to carry forward from their relational histories, a pattern this study termsrelational legacy. Integrating parent-generated language into ERH measurementresearchmay shape a more comprehensive picture of ERHreflectinghow families experience connection.

Background. A filum diameter >2 mm is the conventional MRI threshold for a thickened filum, but it derives from small, mostly adult series showing no age dependence; whether one cutoff suits all of childhood is untested. Objective. To build an age-specific filum-diameter reference on routine pediatric MRI and test, adjusting for image resolution, whether the 2-mm threshold is age-stationary. Materials and methods. In this retrospective study an nnU-Net tracer measured the maximal filum diameter on consecutive lumbosacral MRI; versus manual tracing it showed negligible bias but moderate single-measure agreement. After excluding report-confirmed fatty filum, lipoma, or tethered cord, the proportion >2 mm was analysed within one acquisition protocol and by logistic regression adjusting for voxel size and slice thickness. Results. Of 7,245 examinations, 3,869 (53%) were traceable; untraced ones were younger (median 0.75 vs 2.0 years). The presumed-normal cohort had median diameter 1.48 mm. At matched resolution, 2 mm marked the 94th percentile in infants (5.6% exceeded it) but the 83rd by 3-6 years (17.4%); the age effect persisted after adjusting for voxel size and slice thickness (3-6 years vs infants, adjusted OR 4.7; P < .001). Conclusion. Filum diameter clusters near 1.5 mm, and the fixed 2-mm cutoff flags ~5% of infants but ~17% of preschoolers. Caliber should be judged against an age-specific clinical reference, not one fixed cutoff; a thick filum is not itself a diagnosis of tethered cord.