The diagnostic yield of genetic and metabolic investigations in syndromic and nonsyndromic patients with autism spectrum disorder, global developmental delay, or intellectual disability from a dedicated neurodevelopmental disorders genetics clinic.

First-tier genetic investigations for patients with neurodevelopmental disorders (NDDs) may include chromosomal microarray, Fragile X testing, and screening for inherited metabolic diseases, but most remain undiagnosed upon completion of testing. Here, we report the diagnostic yields of genetic testing for 537 patients with at least one of autism spectrum disorder, global developmental delay, and/or intellectual disability. Patients were assessed in a single neurodevelopmental genetics clinic, and each underwent a standardized history and physical examination. Each patient was characterized as syndromic or nonsyndromic based on clinical features. Our results demonstrate that multigene sequencing (with an NDD gene panel or exome) had a higher diagnostic yield (8%; 95% confidence interval [CI]: 5%, 13%) than chromosomal microarray and Fragile X testing combined (4%; 95% CI: 3%, 7%). Biochemical screening for inherited metabolic diseases had a diagnostic yield of zero. The diagnostic yield of genetic testing was significantly higher for syndromic patients than for nonsyndromic patients (odds ratio [OR] 3.09; 95% CI: 1.46, 6.83) and higher for female patients than for male (OR 3.21; 95% CI: 1.52, 6.82). These results add to the growing evidence supporting a comprehensive genetic evaluation that includes both copy number analysis and sequencing of known NDD genes for patients with NDDs.

Does Celecoxib Prescription for Pain Management Affect Post-tonsillectomy Hemorrhage Requiring Surgery? A Retrospective Observational Cohort Study.

BACKGROUND: Adenotonsillectomy and tonsillectomy (referred to as tonsillectomy hereafter) are common pediatric surgeries. Postoperative complications include hemorrhage requiring surgery (2 to 3% of cases) and pain. Although nonsteroidal anti-inflammatory drugs are commonly administered for postsurgical pain, controversy exists regarding bleeding risk with cyclooxygenase-1 inhibition and associated platelet dysfunction. Preliminary evidence suggests selective cyclooxygenase-2 inhibitors, for example celecoxib, effectively manage pain without adverse events including bleeding. Given the paucity of data for routine celecoxib use after tonsillectomy, this study was designed to investigate the association between postoperative celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery using chart-review data from the Children's Hospital of Eastern Ontario. METHODS: After ethics approval, a retrospective single-center observational cohort study was performed in children less than 18 yr of age undergoing tonsillectomy from January 2007 to December 2017. Cases of adenoidectomy alone were excluded due to low bleed rates. The primary outcome was the proportion of patients with post-tonsillectomy hemorrhage requiring surgery. The association between a celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery was estimated using inverse probability of treatment weighting based on propensity scores and using generalized estimating equations to accommodate clustering by surgeon. RESULTS: An initial patient cohort of 6,468 was identified, and 5,846 children with complete data were included in analyses. Median (interquartile range) age was 6.10 (4.40, 9.00) yr, and 46% were female. In the cohort, 28.1% (n = 1,644) were prescribed celecoxib. Among the 4,996 tonsillectomy patients, 1.7% (n = 86) experienced post-tonsillectomy hemorrhage requiring surgery. The proportion with post-tonsillectomy hemorrhage requiring surgery among patients who had a tonsillectomy and were or were not prescribed celecoxib was 1.94% (30 of 1,548; 95% CI, 1.36 to 2.75) and 1.62% (56 of 3,448; 95% CI, 1.25 to 2.10), respectively. Modeling did not identify an association between celecoxib prescription and increased odds of post-tonsillectomy hemorrhage requiring surgery (odds ratio = 1.4; 95% CI, 0.85 to 2.31; P = 0.20). CONCLUSIONS: Celecoxib does not significantly increase the odds of post-tonsillectomy hemorrhage requiring surgery, after adjusting for covariates. This large pediatric cohort study of celecoxib administered after tonsillectomy provides compelling evidence for safety but requires confirmation with a multisite randomized controlled trial.

Investigating the Risk Factors Associated With Acute Neurologic Dysfunction in Pediatric Hyperglycemic Emergencies on Transport.

OBJECTIVE: This study aims to identify key characteristics of hyperglycemic emergencies in pediatric patients and those at risk for acute neurologic dysfunction during transport. METHODS: We conducted a retrospective chart review of pediatric patients during interfacility transport by Ornge, Ontario's critical care transport service, from January 1, 2009, to December 31, 2019. Data were extracted from electronic patient care records and included demographic, clinical, and transport-specific variables. Two multiple logistic regression models were utilized to analyze associations between predictor variables and neurologic dysfunction (GCS, <14). RESULTS: Of the 399 patients included, 24% (n = 95) had a GCS score of <14. Patients with a GCS score of <14 were more acidotic compared with those with a GCS score of ≥14 (median pH, 6.9 [IQR, 6.8-7.1] vs median, pH 7.0 [IQR, 1.0-7.2]; P < 0.001). Higher median corrected sodium for glucose values were observed in patients with a GCS score of <14 compared to those with a GCS score of ≥14 (145.7 mmol/L [IQR, 140.6-149.9 mmol/L] vs 141.7 mmol/L [IQR, 138.3-146.4 mmol/L]; P < 0.001). Multiple logistic regression identified younger age (aOR, 0.91; 95% CI, 0.84-0.98; P = 0.01), severe acidosis (pH <7.10; aOR, 3.56; 95% CI, 1.33-11.62; P = 0.02), and higher creatinine (aOR, 1.01; 95% CI, 1.01-1.02; P < 0.001) as risk factors for acute neurologic dysfunction. CONCLUSIONS: Our findings reveal associations between acute neurologic dysfunction, younger age, severe acidosis, and elevated corrected sodium for glucose values in pediatric hyperglycemic emergencies during transport. Education and adherence to guidelines are recommended to improve outcomes in this population.

Normative values of renin and aldosterone in clinically stable preterm neonates.

BACKGROUND: There is a paucity of literature on the normative levels of plasma renin concentration (PRC) and serum aldosterone (SA) in premature neonates. This study aims to provide normative data on PRC and SA levels in preterm neonates in the first 2 weeks after birth and explore associations with maternal, perinatal, or postnatal factors. METHODS: Neonates born at 26- to 34-week gestation were recruited from two neonatal intensive care units in Canada and Australia. The direct renin assay PRC and SA were analyzed on day 1 and days 14-21 after birth to compare across categorical variables and to produce normative values. RESULTS: A total of 262 subjects were enrolled from the Canadian (29%) and Australian (71%) sites. The mean gestational age was 30 weeks, with a mean birth weight of 1457 g. The normative values of PRC and SA for neonates born between 26 + 0 and 29 + 6 weeks and 30 + 0 and 34 + 0 weeks of gestation were produced for day 1 and day 14-21 after birth. Both PRC and SA increased from day 1 to day 14-21. The more premature neonates reached a higher PRC on days 14-21 after birth but exhibited lower SA levels on day 1 after birth. When comparing gender, birth weight, and maternal risk factor categories, no statistical differences in PRC or SA were found. A small but significant decrease in PRC, but not SA, was noted for neonates with placental pathology. CONCLUSIONS: This study produced normative values of PRA and SA in clinically stable preterm neonates that can be referenced for use in clinical practice. A higher resolution version of the Graphical abstract is available as Supplementary information.

Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean.

Seawater Mg:Ca and Sr:Ca ratios are biogeochemical parameters reflecting the Earth-ocean-atmosphere dynamic exchange of elements. The ratios' dependence on the environment and organisms' biology facilitates their application in marine sciences. Here, we present a measured single-laboratory dataset, combined with previous data, to test the assumption of limited seawater Mg:Ca and Sr:Ca variability across marine environments globally. High variability was found in open-ocean upwelling and polar regions, shelves/neritic and river-influenced areas, where seawater Mg:Ca and Sr:Ca ratios range from ∼4.40 to 6.40 mmol:mol and ∼6.95 to 9.80 mmol:mol, respectively. Open-ocean seawater Mg:Ca is semiconservative (∼4.90 to 5.30 mol:mol), while Sr:Ca is more variable and nonconservative (∼7.70 to 8.80 mmol:mol); both ratios are nonconservative in coastal seas. Further, the Ca, Mg, and Sr elemental fluxes are connected to large total alkalinity deviations from International Association for the Physical Sciences of the Oceans (IAPSO) standard values. Because there is significant modern seawater Mg:Ca and Sr:Ca ratios variability across marine environments we cannot absolutely assume that fossil archives using taxa-specific proxies reflect true global seawater chemistry but rather taxa- and process-specific ecosystem variations, reflecting regional conditions. This variability could reconcile secular seawater Mg:Ca and Sr:Ca ratio reconstructions using different taxa and techniques by assuming an error of 1 to 1.50 mol:mol, and 1 to 1.90 mmol:mol, respectively. The modern ratios' variability is similar to the reconstructed rise over 20 Ma (Neogene Period), nurturing the question of seminonconservative behavior of Ca, Mg, and Sr over modern Earth geological history with an overlooked environmental effect.

Climate action, staff engagement, and change management: A paediatric hospital case study.

Planetary health and triple bottom line accounting are concepts healthcare organizations are starting to grapple with. While a few Canadian hospitals are early pioneers in efforts to deliver healthcare with less greenhouse gases, many hospitals struggle with adding a climate lens to their operations. This case study highlights a five year journey at CHEO to roll-out a hospital-wide climate strategy. CHEO has created new reporting structures, revised resource allocation, and launched net-zero targets. This hospital net-zero case study is an illustration of climate actions, given certain contexts, rather than a roadmap. Establishing this hospital-wide strategic pillar-during a global pandemic-has yielded (i) cost savings, (ii) an inspired workforce, and (iii) meaningful greenhouse gas reductions.

A climate resilience maturity matrix for Canadian health systems.

Healthcare decision-makers are becoming increasingly aware that climate change poses significant threats to population health and continued delivery of quality care. Challengingly, responding to climate change requires complex, often expensive, and multi-faceted actions to limit new emissions from worsening climate trajectories, while investing in climate-resilient systems. We present a Climate Resilience Maturity Matrix that brings together both mitigation and adaptation actions into a high-level tool for health leaders, for supporting organizational review, assessment, and decision-making for climate change readiness. This tool is designed to (i) support leaders in Canadian health facilities and regional health authorities in designing mitigation and adaptation roadmaps, (ii) support decision-making for climate change-related strategic planning processes, and (iii) create a high-level overview of organizational readiness. This tool is intended to consolidate key data, provide a clear communication tool, allow for objective rapid baselining, enable system-level gap analysis, facilitate comparability/transparency, and support rapid learning cycles.

Not so Shocking: Electromyography in Pediatrics Remains Feasible and Diagnostically Useful.

BACKGROUND: Electrodiagnostic testing, including nerve conduction studies (NCS) and electromyography (EMG), assists with localizing lesions within the peripheral nervous system. NCS/EMG in children can be technically challenging and its relevance has been questioned in the era of affordable genetic testing. NCS/EMG provides information that may not be available in the examination of a young or developmentally delayed child. Our goal was to review the volume and referral sources of NCS/EMG studies and evaluate its feasibility and diagnostic yield at a pediatric tertiary care hospital. METHODS: Retrospective chart review of NCS/EMG studies done in pediatric patients at one center from 2014 to 2019. RESULTS: A total of 725 studies were performed, with a median age of 13.2 years (range 0-18 years). The annual number of studies remained constant throughout the study period. Neurologists and surgeons were the most common referral sources, but an increased number of referrals from geneticists was observed. Most (94.5%) NCS/EMG were done on awake patients, with only 5.5% of studies being terminated early due to tolerability of the patient. Of all studies, 326/725 (44%) demonstrated a neuromuscular abnormality, of which 63.5% (207/326) were acquired conditions. Mononeuropathies and polyneuropathies were the most common electrophysiologic diagnoses. DISCUSSION: Our study indicates that NCS/EMG remains a useful diagnostic tool, both for the diagnosis of acquired neuromuscular conditions but also as an adjunct for interpreting genetic results, as indicated by the recent increase in referrals from geneticists. Overall NCS/EMG is well tolerated and able to be performed without sedation in children of all ages.

Poor adherence to sleep and physical activity guidelines among children with epilepsy.

OBJECTIVE: To assess physical activity and sleep rates in a cohort of children with epilepsy (CWE) and determine if there is a relationship between physical activity and sleep time. METHODS: Children aged 8-14 years with a diagnosis of epilepsy and at least one seizure in the past 12 months were monitored via a wrist-worn activity tracker for 16 weeks, to objectively measure daily physical activity, as assessed by step counts, and sleep time. Adherence to physical activity (≥12,000 steps/day) and sleep recommendations (≥9 h for children aged 8-12 years, or ≥8 h for children aged 13-15 years) was determined. To predict daily activity or nightly sleep, a series of multivariable models incorporating age, sex, day-type (all combinations of weekday or weekend and summer holiday or school), participant (as a random effect), daily physical activity (for models predicting sleep), nightly sleep (for models predicting physical activity), and autoregressive terms of previous sleep or physical activity were constructed, and the best-performing models were selected with Akaike information criterion analysis. RESULTS: Twenty-two children with mild to moderate epilepsy were recruited (54.5% female, median (IQR) age 11 (10, 13) years) and monitored for 16 weeks. They met the recommended level of physical activity only in 38.0% (21.7%, 59.4%), and sleep in 49.1% (30.0%, 68.5%) of days. They met both physical activity and sleep guidelines on the same day in only 17.8% (95% CI 7.1%, 38.0%). There was no association between meeting the recommended levels of daily physical activity and sleep time (p = 0.86, ρ = 0.03). In the best-performing model, age, sex, day type, and participant explained 28.9% of the variance in daily physical activity, with no additional insight provided by measures of sleep time. Age, sex, day type, participant, and daily physical activity explained 17.3% of the variance in nightly sleep time, with a statistically discernable but small association between physical activity and sleep time (1.79 ±â€¯0.53, p = 0.001). CONCLUSION: Our cohort of children with mild to moderate epilepsy showed poor adherence to sleep and physical activity guidelines. There was no clinically relevant association between daily physical activity and sleep among these children who were similarly active to healthy peers. Future studies should assess the effect of increased sleep hygiene and physical activity on overall well-being and seizure control in CWE.

Continuous EEG in a Pediatric Intensive Care Unit: Adherence to Monitoring Criteria and Barriers to Adequate Implementation.

BACKGROUND: Subclinical seizures are common in critically ill children and are best detected by continuous EEG (cEEG) monitoring. Timely detection of seizures requires pediatric intensive care unit (PICU) physicians to identify patients at risk of seizures and request cEEG monitoring. A recent consensus statement from the American Clinical Neurophysiology Society (ACNS) outlines the indications for cEEG monitoring in critically ill patients. However, adherence to these cEEG monitoring criteria among PICU physicians is unknown. Our project had two goals: 1. To assess adherence to cEEG monitoring indications and barriers toward their implementation; 2. To improve compliance with the ACNS cEEG monitoring criteria in our PICU. METHODS: This is a single-institution study. A total of 234 PICU admissions (183 unique patients) were studied. A 6-month retrospective chart review identified PICU patients meeting ACNS criteria for cEEG monitoring, and patients for whom monitoring was requested. This was followed by an 8-week quality improvement project. During this mentorship period, a didactic 15-min lecture and summary handouts regarding the ACNS indications for cEEG monitoring were provided to all PICU physicians. Requests for cEEG monitoring during the mentorship period were compared to baseline adherence to cEEG monitoring recommendations, and barriers toward timely cEEG monitoring were assessed. RESULTS: Nearly every fifth PICU patient met cEEG monitoring indications, and prevalences of patients meeting those indications were similar in the retrospective and the prospective mentorship period (18% vs. 19%). Almost all patients (98%) requiring cEEG as per ACNS criteria met the indication for monitoring already at the time of their PICU admission. During the retrospective period, 23% of patients meeting ACNS criteria had a request for cEEG monitoring, which increased to 83% during the mentorship period. The median delay to cEEG initiation was 16.7 h during the mentorship period, largely due to limited hours of EEG technician availability. Electrographic seizures were identified in 36% of patients monitored, all within the first 120 min of cEEG recording. The majority (79%) of cEEGs informed clinical management. CONCLUSIONS: A brief teaching intervention supplemented by pictographic handouts significantly increased adherence to cEEG monitoring recommendations, and cEEGs guided clinical management. However, there were long delays to cEEG initiation. In order to promptly recognize subclinical seizures in critically ill children, we strongly advocate for a routine screening for cEEG monitoring indications as part of the PICU admission process, and a care model allowing for cEEG initiation around-the-clock.

Nonauscultatory clinical criteria are sensitive for cardiac pathology in low-risk paediatric heart murmurs.

BACKGROUND: Healthy children with likely innocent heart murmurs are frequently referred to cardiologists for reassurance. Existing guidelines that advise against these referrals are not consistently followed partly because they involve subjective auscultatory judgements with which many care providers are uncomfortable. Here, we investigate whether clinical criteria with no subjective auscultatory component are sensitive for cardiac pathology. METHODS: A retrospective chart review was performed of all new patients seen in our paediatric cardiology clinic for assessment of a murmur from January 1, 2016 through June 30, 2018. Patients were characterized as "low-risk" if they met all of the following criteria: asymptomatic; normal physical examination other than the murmur; no risk factors for congenital heart disease; and age over 12 months. The primary outcomes were the sensitivity for ruling out pathology and the negative predictive value of the proposed criteria. RESULTS: Of 915 total patients, 214 met the low-risk criteria. The sensitivity of our criteria for ruling out pathology was 97.2% (95% confidence interval 94.1% to 99.0%) and the negative predictive value was also 97.2% (95% confidence interval 94.0% to 98.7%). Six of the 214 low-risk patients had pathology (2.8%; 95% confidence interval 1.3% to 6.0%), none of which has required intervention since diagnosis. Each of these six children had a murmur that sounded pathological to the auscultating cardiologist. CONCLUSIONS: Basic clinical criteria that do not require auscultation are highly sensitive for ruling out significant cardiac pathology in children over 12 months of age.

No improvement in quality of life in children with epilepsy treated with the low glycemic index diet.

BACKGROUND: Up to 30% of children with epilepsy show a poor therapeutic response to pharmacologic treatment. Ketogenic diets, including the less strict low glycemic index treatment (LGIT), may improve seizure control in pharmacoresistant epilepsy. However, little is known about the quality of life (QoL) in children on LGIT. To explore psychosocial implications of the LGIT on pediatric patients and their caregivers, we have conducted a pilot study to explore the QoL of children and adolescents on the diet. METHODS: Pediatric patients on LGIT and their parents completed standardized, validated QoL questionnaires (Pediatric Quality of Life Epilepsy Module), one retrospectively and one while being on LGIT. An additional questionnaire included two open-ended questions in order to gain a better understanding of personal experiences of families. RESULTS: We enrolled six patients with epilepsy on LGIT between the age of 3 and 13 years. Self-reported QoL decreased in all adolescents, regardless of improvement in seizure control. Parent-reported QoL improved in three of six participants, remained stable in one, and decreased in two patients (both displayed no seizure improvement). Parents and adolescents reported positive experiences of trying new foods and being more health conscious, as well as negative themes such as social isolation and meal preparation difficulties. CONCLUSIONS: The lack of improvement in patient-reported QoL points towards an overall negative impact of the LGIT on patient well-being, despite positive effects on seizure control. Our preliminary results indicate that the benefits of seizure control may subjectively be outweighed by adverse social effects of the LGIT. Families should be made aware of psychosocial risks of the diet. Whenever possible, children should be part of the therapeutic decision-making process. Larger prospective studies are required to fully assess the overall impact of the LGIT.

Physically active children with epilepsy have good objective sleep duration and efficiency despite subjective reports of fatigue and sleep problems.

OBJECTIVE: The aim of this study was to longitudinally characterize in children with epilepsy the objective and subjective sleep quality and the relationship between increased physical activity and sleep as well as measures of psychosocial well-being. METHODS: Baseline physical activity and sleep were established in children with epilepsy over four weeks, prior to a 12-week exercise intervention (weekly meeting with exercise counselor). Participants continuously wore a wrist pedometer (Fitbit Flex®) to capture daily number of steps, sleep efficiency, and total sleep time. The Early Childhood Epilepsy Severity Scale (E-Chess) assessed baseline epilepsy severity. Subjective sleep quality (Children's Sleep Habits Questionnaire, CSHQ), quality of life (KIDSCREEN-27; Pediatric Quality of Life Inventory, PedsQL™, 4.0 Core), fatigue (PedsQL™ Multidimensional Fatigue Scale), depression (Children's Depression Inventory-Short), and anxiety (Multidimensional Anxiety Scale for Children) were assessed pre- and post-interventions. RESULTS: Our cohort of 22 children with epilepsy aged 8-14 years was similarly active to peers (11,271 ±â€¯3189 mean steps per day) and displayed normal sleeping patterns (mean sleep efficiency: 87.4% ±â€¯3.08 and mean total sleep time: 521 ±â€¯30.4). Epilepsy severity assessed by E-Chess was low to moderate (median baseline E-Chess score of 6, interquartile range: 5-7). Study outcomes did not change with the intervention. Older children and those with lower baseline activity were more likely to increase their activity during the intervention. Changes in physical activity were not associated with changes in sleep outcomes when accounting for age, sex, and baseline E-Chess score. Subjective sleep quality marginally improved with the intervention (CSHQ total score: 44.5 ±â€¯5.8 at baseline and 41.6 ±â€¯7.2 at the end of study, p = 0.05). Quality of life, fatigue, depression, and anxiety did not change with the intervention (p = 0.55, 0.60, 0.12, and 0.69, respectively). SIGNIFICANCE: Children with epilepsy who are as active as peers without epilepsy have good objective measures of sleep despite self-reported fatigue and parent-reported sleep problems. The physical activity of initially less active and older children with epilepsy may benefit from an exercise counseling intervention.

Novel Miscanthus genotypes selected for different drought tolerance phenotypes show enhanced tolerance across combinations of salinity and drought treatments.

BACKGROUND AND AIMS: Water deficit and salinity stresses are often experienced by plants concurrently; however, knowledge is limited about the effects of combined salinity and water deficit stress in plants, and especially in C4 bioenergy crops. Here we aim to understand how diverse drought tolerance traits may deliver tolerance to combinations of drought and salinity in C4 crops, and identify key traits that influence the productivity and biomass composition of novel Miscanthus genotypes under such conditions. METHODS: Novel genotypes used included M. sinensis and M. floridulus species, pre-screened for different drought responses, plus the commercial accession Miscanthus × giganteus (M×g.). Plants were grown under control treatments, single stress or combinations of water deficit and moderate salinity stress. Morphophysiological responses, including growth, yield, gas exchange and leaf water relations and contents of proline, soluble sugars, ash and lignin were tested for significant genotypic and treatment effects. KEY RESULTS: The results indicated that plants subjected to combined stresses showed more severe responses compared with single stresses. All novel drought-tolerant genotypes and M×g. were tolerant to moderate salinity stress. Biomass production in M. sinensis genotypes was more resilient to co-occurring stresses than that in M×g. and M. floridulus, which, despite the yield penalty produced more biomass overall. A stay-green M. sinensis genotype adopted a conservative growth strategy with few significant treatment effects. Proline biosynthesis was species-specific and was triggered by salinity and co-occurring stress treatments, mainly in M. floridulus. The ash content was compartmentalized differently in leaves and stems in the novel genotypes, indicating different mechanisms of ion accumulation. CONCLUSIONS: This study highlights the potential to select novel drought-tolerant Miscanthus genotypes that are resilient to combinations of stress and is expected to contribute to a deeper fundamental knowledge of different mechanistic responses identified for further exploitation in developing resilient Miscanthus crops.

Hand hygiene knowledge and practices of family caregivers in inpatient pediatrics.

Family caregivers are essential inpatient pediatric care partners, yet their handwashing knowledge and compliance are rarely studied. Through hand hygiene audits and self-administered questionnaires, we observed 9% compliance, significantly lower than self-reported practice. We suggest interventions to improve caregiver handwashing behaviors to decrease infection transmission risk to hospitalized children.

Pediatric Headache Patients Are at High Risk of Vitamin D Insufficiency.

BACKGROUND: Vitamin D deficiency has been associated with headaches in adults, but data for children with headaches are sparse. OBJECTIVE: To describe vitamin D levels in children with headaches. METHODS: We retrospectively analyzed serum 25(OH)D concentrations in children aged 2-17 years with headaches compared to children with epilepsy at the Children's Hospital of Eastern Ontario between October 1, 2014, and August 19, 2021. Serum 25(OH)D <50 nmol/L was classified as insufficient. RESULTS: Vitamin D concentrations of 353 children (117 with headaches; 236 with epilepsy) were analyzed. The median age in years was 10 (interquartile range [IQR] 5, 14); 50.4% of subjects were female. The median serum 25(OH)D was 56 nmol/L (IQR 41, 69) in children with headaches and 70 nmol/L (IQR 50, 95) in children with epilepsy. Vitamin D insufficiency was present in 42% of children with headaches and 25% of children with epilepsy (P = .002). In a multivariable linear regression model adjusting for age, sex and seasonality, children with headaches had serum 25(OH)D concentrations that were on average 9 nmol/L (95% CI-16.76, -0.96) lower compared to children with epilepsy (P = .029). CONCLUSION: The prevalence of vitamin D insufficiency is higher in children with headaches compared to children with epilepsy. Prospective studies are needed to assess if vitamin D supplementation may have a therapeutic effect on pediatric headaches.

Accuracy of point-of-care SARS-CoV-2 detection using buccal swabs in pediatric emergency departments.

To optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and the laboratory approach is simple, accurate, and rapid. In this prospective cohort study we evaluated the accuracy of a point-of care nucleic acid device using caregiver/patient self-collected buccal swabs. Participants were recruited in 14 Canadian tertiary care pediatric emergency departments. Children <18 years of age deemed to require SARS-CoV-2 testing were eligible. Caregivers or the patient-collected buccal swabs which were tested on the ABBOTT ID NOW. The reference standard was nasopharyngeal swab specimens collected by a healthcare provider tested via laboratory reverse transcription PCR (RT-PCR). We enrolled 2,640 study participants and 14.4% (381/2,640) were SARS-CoV-2 RT-PCR-positive. Eight percent (223/2,640) and 85.0% (2,244/2,640) were concordant test-positive and concordant test-negative, respectively. Sensitivity and specificity of the investigational approach were 58.5% [95% confidence interval (CI): 53.4, 63.5] and 99.3% (95% CI: 98.9, 99.6), respectively. Cycle threshold values were lower among concordant [median 17 (15, 21)] relative to discordant [median 30 (22, 35)] swabs (P < 0.001). Sensitivity was greatest among children <4 years of age, when caregivers performed the swabs, among unvaccinated children, and those with shorter symptom duration. Across multiple pain measures, less pain was associated with buccal swab testing. Although accuracy of the buccal swab point-of-care SARS-CoV-2 test was good and negative agreement was excellent, sensitivity was only 58.5%. Concordance was greater among those with higher viral loads, and the approach involving buccal swabs was less painful.IMPORTANCETo optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and laboratory approach is simple, accurate, and rapid. We evaluated the accuracy and pain associated with buccal swab specimen collection by caregivers or children themselves who were tested using a point-of-care isothermal nucleic acid amplification SARS-CoV-2 test. This novel approach was compared to nasopharyngeal swab specimens tested using laboratory-based PCR tests. While negative agreement was excellent, positive percent agreement was less than 60%. Concordance was greater among those with higher viral loads, and thus, sensitivity is excellent when transmissibility is more likely to occur. Importantly, the approach involving buccal swabs was significantly less painful, and thus, children and their caregivers are more likely to agree to testing using such an approach.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT05040763).

Disruptive camouflage impairs object recognition.

Whether hiding from predators, or avoiding battlefield casualties, camouflage is widely employed to prevent detection. Disruptive coloration is a seemingly well-known camouflage mechanism proposed to function by breaking up an object's salient features (for example their characteristic outline), rendering objects more difficult to recognize. However, while a wide range of animals are thought to evade detection using disruptive patterns, there is no direct experimental evidence that disruptive coloration impairs recognition. Using humans searching for computer-generated moth targets, we demonstrate that the number of edge-intersecting patches on a target reduces the likelihood of it being detected, even at the expense of reduced background matching. Crucially, eye-tracking data show that targets with more edge-intersecting patches were looked at for longer periods prior to attack, and passed-over more frequently during search tasks. We therefore show directly that edge patches enhance survivorship by impairing recognition, confirming that disruptive coloration is a distinct camouflage strategy, not simply an artefact of background matching.