OBJECTIVE:Little is known about the use of intranasal agents in the management of orbital infections in children. This study aims to describe intranasal corticosteroid use in children hospitalized with orbital infections and to determine whether an association exists between intranasal corticosteroids and length of hospital stay. METHODS:A multicenter retrospective cohort study was conducted of children aged 2 months to 18 years with orbital infections, periorbital and orbital cellulitis, admitted to participating hospitals between 2009 and 2018. Baseline characteristics and intranasal corticosteroid use were described. The association between intranasal corticosteroids and length of stay was derived using a multivariable median regression model. RESULTS:Of the 1570 children (935 [59.6%] male, median age 5.4 [IQR 2.4, 9.9] years) admitted for orbital infections, 693 (44.1%) received intranasal corticosteroids during their hospital admission. Median length of stay was 82.6 hours (IQR 48.3, 135.0). Of those who received intranasal corticosteroids, most received mometasone (n = 497, 71.7%). In the adjusted analyses, children who received intranasal corticosteroids had longer hospital stay by 14.9 hours (95% CI 8.4-21.4) as compared with those without intranasal corticosteroids. Findings were similar when the analysis was restricted to children with a diagnosis of orbital cellulitis. CONCLUSION:Intranasal corticosteroid use in hospitalized children with periorbital and orbital cellulitis was associated with a small increase in length of stay, although immortal time bias or confounding by indications may be the primary driver of this given our study design. Further investigation is needed to better determine the effectiveness of intranasal corticosteroid use in children with orbital infections.

BACKGROUND AND PURPOSE:Neonatal encephalopathy (NE) is a risk factor for long-term neurodevelopmental impairments, and early measures of brain function may help understand which survivors are most at risk. This study investigates the relationship between resting-state network (RSN) functional connectivity (FC) in the first week of life and long-term neurodevelopmental outcomes after NE. MATERIALS AND METHODS:A prospective cohort of therapeutic hypothermia-treated neonates ≥36 weeks gestational age with NE had resting-state functional MRI (rs-fMRI) in the first week of life, and follow-up at 18 and 36 months. Subject-wise Pearson correlations between each pair of 27 seeds (seed-to-seed correlation matrix) that represent 6 RSNs of interest (Language, Somatomotor, Default Mode, Frontoparietal, Dorsal attention, Ventral Attention), and subject-wise seed-based mean z scores for each seed were generated. Spearman correlations assessed the associations between 6 intra-RSN FC strength values (averaged subject-wise z-transformed seed-to-seed correlations within each RSN) and 18- and 36-month neurodevelopmental outcomes. Based on primary analyses findings, Spearman correlations also assessed the associations between seed-based mean z scores for specific RSNs and neurodevelopmental outcomes at 36 months. RESULTS:Of 72 neonates, 52 (72%) had adequate quality rs-fMRI data. Based on Barkovich scoring, 3 (6%) neonates had basal ganglia, 2 (4%) had watershed, and 10 (19%) had both brain injury patterns. Of 52, 47 (90%) neonates had follow-up at 19 ± 1.7 months, and 45 (87%) at 36.8 ± 1.5 months. Correcting for multiple comparisons, intra-RSN FC strength was not correlated with 18- or 36-month outcomes. Correcting for multiple comparisons, mean z scores for the right motor, and the right and left supplementary motor area within the Somatomotor RSN were positively correlated with Bayley-III language composite score, and mean z scores for the right temporoparietal junction within the Ventral Attention RSN were positively correlated with Child Behavior Checklist Externalizing Problems composite T-score at 36 months. CONCLUSIONS:RSN FC in the first week of life is correlated with 36-month neurodevelopmental outcomes after NE. Early rs-fMRI could provide meaningful clinical insight for predicting long-term neurodevelopmental outcomes after NE.

Introduction Outcomes following vagus nerve stimulation (VNS) are difficult to predict prior to surgery in pediatric drug-resistant epilepsy (DRE). We investigated whether structural brain differences among children may explain variability in VNS response. Methods A pediatric-specific brain-age model was developed using structural MRI from 2,623 healthy individuals aged 1.9 to 90 years, capturing nonlinear neurodevelopmental trajectories. Model accuracy was evaluated using cross-validation and independent validation in a pediatric cohort. The model was then applied to a multicenter cohort of 126 children with DRE treated with VNS. Results The brain-age model demonstrated high accuracy (R2 = 0.93; mean absolute error = 3.5 years) and generalized well to an independent pediatric cohort (mean absolute error = 2.16 years). Applied to the VNS cohort, it revealed significantly elevated brain-age gaps (BrainAGEgap) compared to age- and sex-matched controls (t = 6.27, p < 0.0001), indicating cumulative structural divergence from age-referenced norms. BrainAGEgap correlated with baseline seizure burden and postoperative changes in seizure frequency. Lower pre-surgical BrainAGEgap predicted a significantly higher likelihood of becoming a clinical responder to VNS (p = 0.01). Local age within the cingulate cortex, thalamus, nucleus accumbens, and prefrontal cortex contributed disproportionately to BrainAGEgap differences, aligning with VNS-related circuitry. Conclusion Developmental structural differences can be summarized using a robust, single-metric biomarker that reflects both disease burden and treatment responsiveness. BrainAGEgap may support individualized prognostic assessment and improve clinical decision-making in pediatric DRE undergoing neuromodulation.

OBJECTIVE:The aims of this study were to examine whether there are distinct biopsychosocial phenotypes among children with drug-resistant epilepsy (DRE) and to determine whether these phenotypes are related to the longitudinal trajectories of child, parent, and family outcomes after epilepsy surgery compared to medical treatment. METHODS:This prospective cohort study recruited children with DRE aged 4-18 years who were evaluated for epilepsy surgery and their parents. Baseline clinical variables, child characteristics, parent depressive and anxiety symptoms, and family factors (household income, family demands, family resources, and satisfaction with family relationships) were used to identify distinct phenotypes using hierarchical k-means clustering. The trajectories of child health-related quality of life (HRQOL), parent depressive and anxiety symptoms, family resources, and satisfaction with family relationships over 2 years in the surgical and medical treatment groups were compared across the phenotypes using linear mixed models. RESULTS:There were 105 surgical and 197 medical patients. Three distinct biopsychosocial phenotypes were identified among children with DRE: the psychosocial vulnerability phenotype had the poorest psychological and social (family) functioning, the well functioning phenotype had substantially better clinical and psychosocial functioning, and the neurological burden phenotype demonstrated the highest seizure burden and intermediate psychosocial functioning. The most pronounced improvements in child HRQOL, parent emotional functioning, and family functioning over time were observed among those with psychosocial vulnerability, especially after epilepsy surgery. The well functioning and neurological burden phenotypes showed more limited change across most outcomes in both treatment groups. SIGNIFICANCE:Identifying biopsychosocial phenotypes may enhance prediction of child, parent, and family outcomes and identify children and families who could benefit from targeted interventions. Despite experiencing more psychosocial disadvantages, the psychosocial vulnerability phenotype demonstrated the largest improvement in outcomes following surgery, suggesting that surgical treatment has the potential to promote more equitable psychosocial outcomes, alongside clinical and HRQOL outcomes.

Objective Although vagus nerve stimulation (VNS) is the most common implantable therapy for drug-resistant epilepsy (DRE), there is a need to develop novel methods to predict treatment response before surgery. An integrated approach combining structural and functional neuroimaging data to infer biophysical brain features at the mesoscopic scale could provide insights into brain-network differences related to response. The Virtual Brain (TVB) offers a computational framework to simulate individual subject brain dynamics using biophysical neural mass models to estimate synaptic transmission properties in the brain. This study aims to (i) assess the ability of TVB-based modeling to capture individual brain dynamics in pediatric DRE, (ii) evaluate the relationship between predictability of brain dynamics using a biophysical approach and VNS outcome, and (iii) identify regional inhibitory features as potential biomarkers of VNS response. Materials and Methods Preimplantation functional and diffusion magnetic resonance imaging data were acquired and used to construct personalized virtual brains using the reduced Wong-Wang model. The model was optimized for individual participants, and both local and global parameters of the models were compared between responders and nonresponders to VNS. Results A total of 38 children with DRE undergoing VNS implantation were included in this multicenter study, including 16 responders and 22 nonresponders. Predictability of the functional connectivity using the biophysical model was significantly lower in nonresponders, implicating atypical brain dynamics in VNS outcomes. TVB simulations showed stronger inhibitory synaptic weights in critical regions of the vagal afferent network in responders compared with nonresponders, including the thalamus, cingulate, and frontal cortices. Conclusions This study constitutes the first work exploring TVB in pediatric DRE and VNS. Personalized brain dynamics simulations revealed distinct inhibitory patterns between responders and nonresponders, offering new insights into the interindividual variability in VNS outcomes and mechanisms of action of VNS therapy.

OBJECTIVE:This cohort study examined the agreement between youth- and parent-reported health-related quality of life (HRQOL) of children treated with epilepsy surgery compared to medical therapy. A second aim was to evaluate whether changes in HRQOL over 2 years differed between the two groups, and to determine whether these trajectories differed by informant (youth or parent). METHODS:A total of 255 youth-parent dyads participated, of whom 95 youth underwent epilepsy surgery and 160 continued medical management. Participants completed the KIDSCREEN-27 at baseline, 6-month, 1-year, and 2-year follow-up. Youth-parent agreement was evaluated at the individual level as well as at the group level. Linear mixed models were used to evaluate changes in HRQOL over time. RESULTS:Among 255 youth, 46% were female, and ages ranged from 8 to 18 years (mean 13 years) at baseline. Most parents were female (85%) and 40-49 years of age (58%). The surgical and medical group were largely similar across baseline characteristics. Agreement across HRQOL domains ranged from fair to good intraclass correlation coefficient (ICC .32-.66). Although average youth-parent differences were small (-1 to +3 points), Bland-Altman plots showed large discrepancies, and substantial differences between dyads were frequent. Youth reported increasing Physical Well-being and School Environment scores in the first year after surgery and remaining stable or slightly decreasing thereafter. In contrast, parent-reported trajectories for Physical Well-being and School Environment did not show a significant difference. For other domains-Psychological Well-being, Autonomy and Parent Relation, and Social Support and Peers-no differences were identified across treatment groups, and findings were consistent among youth and parent reports. SIGNIFICANCE:The results emphasize the need for considering the perspective of youth as well as their parents when evaluating the outcomes of surgery or other treatments for epilepsy.

BACKGROUND:Cerebral folate transporter deficiency (FOLR1-related CFTD, MIM #613068) is a rare, autosomal recessive neurological disease characterized by markedly deficient CSF folate levels arising from impaired transport of folate across the blood-brain barrier. Current research highlights the role of folinic acid in treatment for patients with CFTD. To date, there has been minimal published evidence on seizure management for CFTD patients whose conditions are refractory to folinic acid treatment, and there are no standardized approaches for guiding care in this subset. OBSERVATIONS:The authors report a successful clinical outcome after corpus callosotomy in a patient with drug-resistant epilepsy (DRE) secondary to folinic acid-refractory CFTD. LESSONS:This case represents the first documented surgical treatment for DRE in this patient population. Intracranial epilepsy surgery might play an important role for managing DRE in this patient population in the future. https://thejns.org/doi/10.3171/CASE25793.

OBJECTIVE:Although vagus nerve stimulation (VNS) is a well-established neuromodulation therapy for drug-resistant epilepsy, treatment outcomes remain heterogeneous. One possible source of variability lies in differing interpretations of seizure frequency ratings (SFRs). This study examined interrater reliability (IRR) in SFRs between (1) retrospective clinician-clinician chart reviews and (2) prospective caregiver-clinician reports, and explored sources of disagreement. METHODS:Data were collected from the CONNECTiVOS database. In the retrospective cohort (n = 254), two clinicians independently reviewed medical records and rated seizure frequency across multiple timepoints. In the prospective cohort (n = 214), caregivers and clinicians independently reported SFR in children treated with VNS. IRR was assessed across different measurement thresholds, and potential causes of disagreement were analyzed. RESULTS:Clinician-clinician agreement in retrospective chart reviews was excellent (intraclass correlation coefficient [ICC] > .90, Cohen κ > .80), with 18.8% divergent ratings and 4.8% exceeding the reliable change index. Disagreement was significantly associated with higher mean seizure frequency at baseline (p = .004) and at postoperative timepoints (p < .001). In the prospective caregiver-clinician comparison, agreement for absolute seizure frequency was poor (ICC < .50), with discrepancies in 86.5% of cases, although only 1.8% were statistically significant. When rating pairs diverged, clinicians more often reported lower absolute seizure frequencies (p = .002) and greater relative seizure reductions (p = .023) and were more likely to classify patients as achieving a 90% reduction (p = .043). SIGNIFICANCE:This study highlights interrater variability in both retrospective and prospective SFR assessments, a finding systematically related to baseline seizure frequency. Coarser classifications (e.g., 50% or 90% seizure reduction) may improve agreement but reduce clinical nuance. Future efforts should focus on structured, patient-centered documentation and the development of objective outcome measures in VNS evaluation, particularly for children with high seizure burden.

The aim of this study is to delineate technical considerations for subcortical electrode targeting in children with DRE and to present a target selection decision-support tool for pediatric neurosurgeons for DBS and RNS. A systematic review of studies through age ≤ 19 years reporting DBS or RNS implantation for DRE was performed. Articles were screened for details on trajectory planning, imaging parameters, intraoperative workflows, and direct versus indirect targeting strategies. Primary outcomes were seizure-frequency reduction and responder rate; secondary outcomes included perioperative adverse events and identification of pediatric-specific factors influencing surgical planning. Seventeen studies (10 DBS, 7 RNS; total n = 333 children) met inclusion criteria. Median age was 16.0 ± 6.35 years; median epilepsy duration was 12.15 ± 7.98 years; 41.4

The objective of this study was to examine the association between early brain MRI T2 hyperintensity and neurodevelopmental outcomes in term infants with neonatal encephalopathy. A prospective cohort of neonates born ≥ 36 weeks postmenstrual age with neonatal encephalopathy underwent brain MRI in the early postnatal period. Scans were graded for T2 hyperintensity using Kidokoro scoring, and diffusion restriction using Barkovich scoring. The association between T2 hyperintensity (diffuse, mamillary body, pons) and Bayley-III cognitive, language, and motor composite scores at 3 years was examined using multivariable linear regression modeling. The cohort included 102 term infants (63

As many as 80 million people in the world have epilepsy. Those living in the developing world are disproportionately affected. Approximately 770,000 people in Uganda are affected by epilepsy. Drug-resistant epilepsy affects approximately 30%-40% of patients with epilepsy, and one-third of these patients may be eligible for surgical management. This article describes the formation of an epilepsy monitoring unit in Uganda as the first step toward establishing a surgical epilepsy program for pediatric patients. A hybrid remote and in-person collaborative model was developed between teams in Mbale and Kampala in Uganda and Chicago in the US. The authors describe a process that spanned 2 years (2021-2023) for developing readiness for referrals for pediatric epilepsy surgery candidates in Uganda.

OBJECTIVES:Responsiveness to vagus nerve stimulation (VNS) in children with drug-resistant epilepsy (DRE) is often defined based on reduction in seizure frequency, typically at the 50% threshold, with limited consideration to the effects of therapy on seizure severity and health-related quality of life (HRQoL). In the current report, we sought to better characterize the effects of VNS beyond seizure frequency in children with DRE. METHODS:Sixty-seven children from the Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS) database, a multicenter study including children aged 0-18 who underwent VNS at eight North American centers, were included. Data were collected prospectively at baseline and 6, 12, and 24 months after VNS. Seizure outcomes were assessed using the 50% threshold, percentage change in seizure count and change on a frequency timescale, a categorical measure of seizure occurrence (e.g., daily to weekly seizures). The Seizure Severity Questionnaire and the Quality of Life in Childhood Epilepsy were also collected. Linear mixed models were constructed to study longitudinal changes in seizure severity and HRQoL. RESULTS:Among 67 children, 55.2% experienced >50% reduction in seizures, whereas only 37.3% demonstrated reductions in seizure timescales. Notably, 17.9% experienced no reduction in timescales despite meeting the 50% threshold. Furthermore, 31.9% of children experienced a meaningful improvement in seizure severity without any reduction in seizure timescales. HRQoL improvements were driven by the reduction in timescales (mean yearly increase of 3.65; 95% confidence interval [CI]: 0.71-6.52, p = 0.023), rather than responsiveness based on the 50% threshold or percentage change in seizure counts (p > 0.05). Reduced overall seizure severity was also independently associated with higher HRQoL after VNS (p = 0.035). SIGNIFICANCE:The conventional 50% responder threshold failed to capture meaningful gains in HRQoL, which aligned more closely with seizure timescales. Furthermore, nearly one-third of children realized improvements in seizure severity without any reduction in timescales. Improvements in both seizure frequency timescales and seizure severity drive postoperative HRQoL gains.

OBJECTIVE A minority of pediatric patients who may benefit from epilepsy surgery receive it. The reasons for this utilization gap are complex and not completely understood. Patient and caregiver social determinants of health (SDOH) may impact which patients undergo surgery and when. The authors conducted a systematic review examining SDOH and surgical intervention in children with drug-resistant epilepsy (DRE). They aimed to understand which factors influenced time to surgical program referral or receipt of epilepsy surgery among children with DRE, as well as identify areas to characterize the SDOH impacting epilepsy surgery in children and guide efforts aimed to promote health equity in epilepsy. METHODS A systematic review was conducted using the PubMed, Embase, and Scopus databases in January 2022. Studies were analyzed by title and abstract, then full text, to identify all studies examining the impact of SDOH on utilization of epilepsy surgery. Studies meeting inclusion criteria were analyzed for SDOH examined, outcomes, and key findings. Quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS Of 4545 resultant articles, 18 were included. Studies examined social, cultural, and environmental factors that contributed to SDOH impacting epilepsy surgery. Patients who underwent surgical evaluation were found to be most commonly White and privately insured and have college-educated caregivers. Five studies found differences in time to referral/surgery or rates of surgery by racial group, with most finding an increased time to referral/surgery or lower rates of surgery for those who were Hispanic and/or non-White. Four studies found that private insurance was associated with higher surgical utilization. Three studies found higher household income was related to surgical utilization. No studies examined biological, psychological, or behavioral factors that contributed to SDOH impacting epilepsy surgery. CONCLUSIONS The authors conducted a systematic review exploring the impact of SDOH in DRE surgery utilization. They found that race, ethnicity, insurance type, caregiver educational attainment, and household income demonstrate relationships with pediatric epilepsy surgery. Further study is necessary to understand how these factors, and others not identified in this study, contribute to the low rates of utilization of epilepsy surgery and potential target areas for interventions aiming to increase equity in access to epilepsy surgery in children.

OBJECTIVE We identified factors associated with computed tomographic (CT) imaging within 24 hours of emergency department (ED) presentation in hospitalized children with severe orbital infections.PATIENTS AND METHODS A multicenter retrospective cohort study was conducted that included children aged 2 months to 18 years between 2009 and 2018 who were admitted to the hospital with severe orbital infections, including periorbital and orbital cellulitis. Multivariable modified Poisson regression was used to identify possible factors associated with receiving a CT scan within 24 hours of ED presentation.RESULTS Of 1144 children, 494 (43.2%) received a CT scan within 24 hours of ED presentation. Factors associated with receiving a CT scan within 24 hours included sex (male; adjusted relative risk [aRR], 1.18; 95% CI, 1.04-1.33), hospitalized at a children's hospital (aRR, 1.80; 95% CI, 1.32-2.45), consulted by both ophthalmology and otolaryngology (aRR, 3.12; 95% CI, 2.35-4.13) or either ophthalmology (aRR, 2.19; 95% CI, 1.66-2.90) or otolaryngology (aRR, 2.66; 95% CI, 1.84-3.86), and had proptosis (aRR, 1.39; 95% CI, 1.24-1.57) or eye swollen shut (aRR, 1.27; 95% CI, 1.13-1.43) as clinical signs upon ED presentation. Children aged younger than 5 years were less likely to receive early CT imaging (aRR, 0.63; 95% CI, 0.53-0.74). There were no associations between time of ED triage, temperature greater than 38 degrees C, or inflammatory markers with early CT imaging.CONCLUSION Although several patient and hospital factors associated with early CT imaging decisions in children with severe orbital infections are associated with more severe infections, newly identified risk factors, such as inflammatory markers, were not. These findings will help better the understanding of clinical management and indications for CT imaging.

AIM:To describe the rates of stroke and craniocervical vasculopathy progression in children with posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities (PHACE) syndrome. METHOD:A single-center, retrospective natural history study of children with PHACE syndrome. Clinical and sequential neuroimaging data were reviewed to study the characteristics and progression of vasculopathy and calculate the rates of arterial ischemic stroke (AIS) and transient ischemic stroke (TIA). Vasculopathy progression was defined as worsening or new vascular findings on follow-up magnetic resonance angiography. RESULTS:Thirty-four children with cerebrovascular abnormalities at the PHACE syndrome diagnosis were studied (age range = 2 to 18 years, 85% females). Median age at the initial diagnosis was 5.5 months (interquartile range = 1-52 months); median age at the last follow-up was 8 years 6 months (range = 2-18 years). Overall, 10 (29%) patients had radiological progression of their vasculopathy, with a cumulative progression-free rate of 73% (95% confidence interval [CI] = 0.57-0.89), and a cumulative TIA-free and AIS-free rate of 87% (95% CI = 0.745-0.99). Vasculopathy was continuously progressive in six patients (18%) at the last follow-up. Three patients (9%) had TIA and all had progressive vasculopathy. One patient had presumed perinatal AIS at the initial PHACE diagnosis, while no other patient experienced an AIS during the follow-up. INTERPRETATION:In children with PHACE syndrome, craniocervical vasculopathy is non-progressive and asymptomatic in the majority of cases. The risk of ischemic stroke in these children is very low. Larger and prospective studies are necessary to confirm these findings. WHAT THIS PAPER ADDS:Cerebrovascular vasculopathy in children with PHACE syndrome is predominantly non-progressive and asymptomatic. Cerebrovascular vasculopathy in children with PHACE syndrome is associated with a low risk of stroke during childhood. In children with progressive vasculopathy, neuroimaging progression was generally slow over the first years of life.

Background Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. Objective We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. Methods This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. Results Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. Conclusions Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.

Child health-related quality of life (HRQOL) has been shown to improve after epilepsy surgery and is linked to parent HRQOL. We postulated that the HRQOL of parents whose children underwent epilepsy surgery would improve over two years compared to those treated with medical therapy. The aim of the study was to evaluate the trajectory of HRQOL of parents whose children received treatment with epilepsy surgery or medical therapy over two years. This multi-center study recruited parents whose children were evaluated for epilepsy surgery. Parents completed measures of care-related QOL (CarerQOL) at the time of their children’s surgical evaluation, 6 months, 1 year, and 2 years later. Additional measures included parent anxiety and depression, satisfaction with family relationships, family resources and demands, and child clinical variables. A linear mixed model was used to compare the trajectories of parent HRQOL of surgical and medical patients, adjusting for baseline clinical, parent, and family characteristics. There were 111 children treated with surgery and 154 with medical therapy. The trajectory of parent HRQOL was similar among parents of surgical and medical patients over the two-year follow-up. However, HRQOL of parents of surgical patients was 3.0 points higher (95

Objective To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections. Design Multi-centre observational cohort study using data from 2009 to 2018 clinical records. Setting Canadian children's hospitals (7) and community hospitals (3). Patients Children between 2 months and 18 years hospitalised for >24hours with severe orbital infections. Interventions Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation. Main outcome measures Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates. Results Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8hours (third generation cephalosporin and anaerobic coverage) to 19.5hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018. Conclusions Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.