Improving inpatient paediatric de-labelling of allergies to beta-lactams: a quality improvement study.

OBJECTIVE: To evaluate the implementation of an antimicrobial stewardship programme-led inpatient beta-lactam allergy de-labelling programme using a direct oral provocation test (OPT). DESIGN: One-year quality improvement study using a before-after design. SETTING: Free-standing tertiary care paediatric hospital. PATIENTS: Patients with a reported beta-lactam allergy admitted to the paediatric medicine inpatient unit. INTERVENTIONS: Following standardised assessment and risk stratification of reported symptoms, patients with a low-risk history were offered an OPT. Beta-lactam allergy labels were removed if a reported history was considered non-allergic or after successful OPT. MAIN OUTCOME MEASURES: Removal of inappropriate beta-lactam allergy labels. RESULTS: 80 patients with 85 reported beta-lactam allergies were assessed. Median age was 8.1 years (IQR 4.8-12.9) and 34 (42%) were female. The majority (n=55, 69%) had an underlying medical condition. Amoxicillin was the most reported allergy (n=25, 29%). Reported reactions were primarily dermatological (n=65, 77%). Half of participants (n=40) were ineligible for OPT, with equal proportions due to clinical reasons or the nature of the reported reaction. Of the 40 eligible patients, 28 patients (70%) were de-labelled either by history alone (n=10) or OPT (n=18). All OPTs were successful. De-labelling allowed five additional patients (11% of those receiving antibiotics) to receive the preferred beta-lactam. Including patients who were subsequently assessed in the allergy clinic, almost half of all evaluated patients were de-labelled (n=37, 46%). CONCLUSIONS: An antimicrobial stewardship programme-led programme using a direct OPT was feasible and safe for expanding beta-lactam allergy de-labelling to paediatric patients admitted to the paediatric medicine inpatient unit.

Viral dynamics of the SARS-CoV-2 Omicron Variant in Paediatric Patients; A prospective cohort study.

BACKGROUND: There are limited data on the viral dynamics of SARS-CoV-2 in children. Understanding viral load changes over the course of illness and duration of viral shedding may provide insight into transmission dynamics to inform public health and infection control decisions. METHODS: We conducted a prospective cohort study of children 18 years and younger with PCR confirmed SARS-CoV-2 between February 1, 2022 and March 14, 2022. SARS-CoV-2 testing occurred on daily samples for 10 days; a subset of participants completed daily rapid antigen testing (RAT). Viral RNA trajectories were described in relation to symptom onset and resolution. The associations between both time since symptom onset/resolution and non-infectious viral load were evaluated using a Cox proportional hazards model. FINDINGS: Among 101 children aged 2 to 17 years, the median time to study-defined non-infectious viral load was 5 days post symptom onset, with 75% meeting this threshold by 7 days, and 90% by 10 days. On the day of and day after symptom resolution, 43 of 87 (49%) and 52 (60%) had met the non-infectious thresholds, respectively. Of the 50 participants completing RAT, positivity at symptom onset and on the day after symptom onset was 67% (16/24) and 75% (14/20). On the first day where the non-infectious threshold was met, 61% (n = 27/44) of participant RAT results were positive. INTERPRETATION: Children often met the study-defined non-infectiousness threshold on the day after symptom resolution. RAT tests were often negative early in the course of illness and should not be relied on to exclude infection. CLINICAL TRIALS REGISTRATION: NCT05240183.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Rise in the incidence of severe pediatric blepharokeratoconjunctivitis during the COVID-19 pandemic.

Severe blepharokeratoconjunctivitis (BKC) is associated with vision loss and ocular morbidity; hence, early diagnosis and treatment are crucial. Retrospective data collection using electronic patient and billing database records of all patients <18 years of age with severe BKC between March 2010 and March 2022 was performed at the Eye Clinic at the Hospital for Sick Children in Toronto, Canada. Severe BKC was defined as including corneal inflammation, new vessel formation, scarring, thinning and lipid deposits. We excluded patients with mild or no corneal involvement, and those with other corneal pathologies. Over the study period, 257 patients were diagnosed with severe BKC (161 females), with an average age of 8 years. There was a statistically significant threefold increase in the diagnosis of severe BKC since the beginning of the COVID-19 pandemic in 2020 compared to the previous years. We speculate that the increased use of facial masks during the pandemic contributed to this significant increase.

Heated humidified high flow nasal cannula therapy in children with obstructive sleep apnea: A randomized cross-over trial.

OBJECTIVE/BACKGROUND: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in children with obesity and/or underlying medical complexity. The first line of therapy, adenotonsillectomy (AT), does not cure OSA in more than 50% of these children. Consequently, continuous positive airway pressure (CPAP) is the main therapeutic option but adherence is often poor. A potential alternative which may be associated with greater adherence is heated high-flow nasal cannula (HFNC) therapy; however, its efficacy in children with OSA has not been systematically investigated. The study aimed to compare the efficacy of HFNC with CPAP to treat moderate-to-severe OSA with the primary outcome measuring the change from baseline in the mean obstructive apnea/hypopnea index (OAHI). PARTICIPANTS/METHODS: This was a single-blinded randomized, two period crossover trial conducted from March 2019 to December 2021 at a Canadian pediatric quaternary care hospital. Children aged 2-18 years with obesity and medical complexity diagnosed with moderate-to-severe OSA via overnight polysomnography and recommended CPAP therapy were included in the study. Following diagnostic polysomnography, each participant completed two further sleep studies; a HFNC titration study and a CPAP titration study (9 received HFNC first, and 9 received CPAP first) in a random 1:1 allocation order. RESULTS: Eighteen participants with a mean ± SD age of 11.9 ± 3.8 years and OAHI 23.1 ± 21.7 events/hour completed the study. The mean [95% CI] reductions in OAHI (-19.8[-29.2, -10.5] vs. -18.8 [-28.2, -9.4] events/hour, p = 0.9), nadir oxygen saturation (7.1[2.2, 11.9] vs. 8.4[3.5, 13.2], p = 0.8), oxygen desaturation index (-11.6[-21.0, -2.3] vs. -16.0[-25.3, -6.6], p = 0.5) and sleep efficiency (3.5[-4.8, 11.8] vs. 9.2[0.9, 15.5], p = 0.2) with HFNC and CPAP therapy were comparable between conditions. CONCLUSION: HFNC and CPAP therapy yield similar reductions in polysomnography quantified measures of OSA severity among children with obesity and medical complexities. TRIAL REGISTRATION: NCT05354401 ClinicalTrials.gov.

Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa.

BACKGROUND: Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. METHODS: In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. FINDINGS: Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. INTERPRETATION: Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. FUNDING: American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

Effect of Wearing a Face Mask on Hand-to-Face Contact by Children in a Simulated School Environment: The Back-to-School COVID-19 Simulation Randomized Clinical Trial.

Importance: Wearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation. Objective: To evaluate the effect of wearing a face mask on hand-to-face contact by children while at school. Design, Setting, and Participants: This prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes. Interventions: Participants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be maintained (grade 5 and up). Main Outcomes and Measures: The primary outcome was the number of hand-to-face contacts per student per hour on day 2 of the simulation. Secondary outcomes included hand-to-mucosa contacts and hand-to-nonmucosa contacts. A mixed Poisson regression model was used to derive rate ratios (RRs), adjusted for age and sex with a random intercept for class with bootstrapped 95% CIs. Results: A total of 174 students underwent randomization and 171 students (mask group, 50.6% male; control group, 52.4% male) attended school on day 2. The rate of hand-to-face contacts did not differ significantly between the mask and the control groups (88.2 vs 88.7 events per student per hour; RR, 1.00; 95% CI, 0.78-1.28; P = >.99). When compared with the control group, the rate of hand-to-mucosa contacts was significantly lower in the mask group (RR, 0.12; 95% CI, 0.07-0.21), while the rate of hand-to-nonmucosa contacts was higher (RR, 1.40; 95% CI, 1.08-1.82). Conclusions and Relevance: In this clinical trial of simulated school attendance, hand-to-face contacts did not differ among students required to wear face masks vs students not required to wear face masks; however, hand-to-mucosa contracts were lower in the face mask group. This suggests that mask wearing is unlikely to increase infection risk through self-inoculation. Trial Registration: ClinicalTrials.gov Identifier: NCT04531254.

How essential are in-person clinic visits during maintenance treatment of children with acute lymphoblastic leukemia?

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Treatment consists of an initial intensive phase of chemotherapy, followed by a prolonged period of maintenance chemotherapy intended to reduce the risk of relapse. During the COVID-19 pandemic, the need arose to identify and reduce non-essential hospital visits. OBJECTIVE: We aimed to determine which proportion of in-person clinic visits during ALL maintenance therapy was associated with a change of management based on the results of the physical examination. PATIENTS AND METHODS: Medical records of children receiving maintenance chemotherapy for B-precursor ALL between September 2019 and February 2020 were reviewed. Visits with a new finding on physical examination were divided into those where an in-person assessment was deemed essential versus not essential. Finally, we determined the proportion of essential in-person visits that resulted in a change of management. RESULTS: A total of 240 maintenance visits by 75 children were analyzed. An abnormal finding on physical examination was noted during 20 visits (8.3%). Of those, 14 (5.8%) uncovered a new finding, six (2.5%) were classified as "in-person visit essential," and among those six visits, three (1.2%) resulted in a change of patient management (one for acute otitis media, one for wheezing, and one for limp). CONCLUSION: Our findings support the evaluation of care delivery models other than in-person visits during ALL maintenance therapy. A prospective study is required to delineate criteria, benefits/risks, and families' perspectives associated with virtual care delivery and the optimal frequency of in-person visits.

Pediatric cannabis intoxication trends in the pre and post-legalization era.

INTRODUCTION: On April 13, 2017, a bill to legalize cannabis was introduced to the Canadian Parliament and presented to the public. On October 17, 2018, Canada legalized recreational cannabis use. We assessed intoxication severity, reflected by ICU admission rates, risk factors and other characteristics in children who presented to the emergency department (ED) with cannabis intoxication, before and after legalization. METHODS: A retrospective cohort study of children 0-18 years who presented to a pediatric ED between January 1, 2008 and December 31, 2019 with cannabis intoxication. The pre-legalization period was defined from January 1, 2008 to April 12, 2017 and the peri-post legalization period from April 13, 2017 to December 31, 2019. RESULTS: We identified 298 patients; 232 (77.8%) presented in the pre legalization period and 66 (22.1%) in the peri-post legalization period; median age: 15.9 years (range: 11 months-17.99 years). A higher proportion of children were admitted to the ICU in the peri-post legalization period (13.6% vs. 4.7%, respectively; p = .02). While the median monthly number of cannabis-related presentations did not differ between the time periods (2.1 [IQR:1.9-2.5] in the pre legalization period vs. 1.7 [IQR:1.0-3.0] in the peri-post legalization period; p = .69), the clinical severity did. The proportions of children with respiratory involvement (65.9% vs. 50.9%; p = .05) and altered mental status (28.8% vs. 14.2%; p < .01) were higher in the peri-post legalization period. The peri-post legalization period was characterized by more children younger than 12 years (12.1% vs. 3.0%; p = .04), unintentional exposures (14.4% vs, 2.8%; p = .002) and edibles ingestion (19.7% vs. 7.8%; p = .01). Edible ingestion was an independent predictor of ICU admission (adjusted OR: 4.1, 95%CI: 1.2-13.7, p = .02). CONCLUSIONS: The recreational cannabis legalization in Canada is associated with increased rates of severe intoxications in children. Edible ingestion is a strong predictor of ICU admission in the pediatric population.

Early transient dysautonomia predicts the risk of infantile epileptic spasm syndrome onset: A prospective cohort study.

Background: Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS. Methods: Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60 min at every 2-month interval. HRV metrics were calculated from 5 min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric. Results: Infantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2-5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA α1 and increasing CVI in the first 8 months of age. Conclusion: Our data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies.

Excess weight gain in the paediatric bleeding disorders population: Impact of the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has resulted in lifestyle changes for children. The aim of this study was to evaluate the impact of the pandemic on weight/BMI in children with severe bleeding disorders. METHODS: We conducted a retrospective review of patients age 3-18 years with severe bleeding disorders on prophylactic therapy treated at SickKids Hospital (Toronto, Canada) between February 01, 2018 and March 31, 2021. We evaluated the following pre- and post-COVID variables: weight (kg), weight percentile, BMI (kg/m2 ), BMI percentile, HJHS score, and prophylactic dosing (units/kg). RESULTS: One hundred and four patients were included in the final analysis. Diagnoses were as follows:  haemophilia A (n = 92; 70.8%), haemophilia B (n = 17; 13.1%), type 3 von Willebrand disease (n = 11; 8.5%), the remainder were diagnosed with rare factor deficiencies.  Median interval time from pre-COVID measurements to latest follow-up was 12.4 months (IQR 10.32-14.52 months) during which there was a statistically significant increase in median weight percentile +5.75 centiles (from 63rd centile to 68.75th centile). There was a statistically significant increase in mean BMI of +1.03 kg/m2 (P = < .001) while median BMI percentile increased +8.82 centiles (from 53.9th centile to 62.72nd centile) and mean BMI percentile increased 3.42 centiles (from 57.5 centile to 60.9 centile). The group that gained the most weight centiles, BMI and BMI centiles were 5-14 years old. CONCLUSION: There was a trend to weight gain over the study period. More long-term data is required to evaluate the impact of this increase in weight and BMI on children with bleeding disorders.

Housing Need Among Children With Medical Complexity: A Cross-Sectional Descriptive Study of Three Populations.

OBJECTIVE: Children with medical complexity (CMC) are hypothesized to have unique housing and accessibility needs due to their medical fragility and medical technology dependency; however, research on prevalence and types of housing need in CMC is limited. The objective was to describe housing need in families of CMC, and to compare housing need across CMC, children with one chronic condition (Type 1 diabetes; CT1D) and healthy children (HC). METHODS: This cross-sectional descriptive study assessed housing suitability, adequacy, affordability, stress, stability, and accessibility using survey methodology. Participants were caregivers of CMC, CT1D and HC at a tertiary-care pediatric hospital. The association of housing need outcomes across groups was analyzed using logistic and ordinal logistic regression models, adjusting for income, educational attainment, employment status, community type, immigration status, child age, and number of people in household. RESULTS: Four hundred ninety caregivers participated. Caregivers of CMC reported increased risk of housing-related safety concerns (aOR 3.1 [1.3-7.5]), using a common area as a sleeping area (5.6 [2.0-16.8]), reducing spending (4.6 [2.3-9.5]) or borrowing money to afford rent (2.9 [1.2-6.7]), experiencing housing stress (3.3 [1.8-6.0]), and moving or considering moving to access health/community services (15.0 [6.4-37.6]) compared to HC. CONCLUSIONS: CMC were more likely to experience multiple indicators of housing need compared to CT1D and HC even after adjusting for sociodemographic factors, suggesting an association between complexity of child health conditions and housing need. Further research and practise should consider screening for and supporting housing need in CMC.

Incidence and Age- and Sex-Specific Differences in the Clinical Presentation of Children and Adolescents With Avoidant Restrictive Food Intake Disorder.

Importance: To our knowledge, this is the first pediatric surveillance study of children and adolescents with avoidant restrictive food intake disorder (ARFID). Objectives: To examine the incidence and age- and sex-specific differences in the clinical presentation of ARFID in children and adolescents in Canada. Design, Setting, and Participants: In this cross-sectional study, patients with ARFID were identified through the Canadian Paediatric Surveillance Program by surveying 2700 Canadian pediatricians monthly from January 1, 2016, to December 31, 2017. Main Outcomes and Measures: The incidence of ARFID in Canadian children (5-18 years of age) and age- and sex-specific clinical characteristics at presentation. Results: In total, 207 children and adolescents (mean [SD] age, 13.1 [3.2] years; 127 [61.4%] female) were included in this study. The incidence of ARFID in children 5 to 18 years of age was 2.02 (95% CI, 1.76-2.31) per 100 000 patients. Older children and adolescents were more likely to endorse eating too little (5-9 years of age: 76.7%; 95% CI, 58%-88.6; 10-14 years of age: 90.9%; 95% CI, 84.6%-94.8%; 15-18 years of age: 95.6%; 95% CI, 83.6%-98.9%; P = .02), have a loss of appetite (5-9 years of age: 53.3%; 95% CI, 35.4%-70.4%; 10-14 years of age: 74.2%; 95% CI, 66.0%-81.0%; 15-18 years of age: 80.0%; 95% CI, 65.5%-89.4%; P = .03), be medically compromised (mean body mass index z score: 10-14 vs 5-9 years of age: -1.31; 95% CI, -2.0 to -0.6; 15-18 vs 5-9 years of age: -1.35; 95% CI, -2.2 to -0.5; 15-18 vs 10-14 years of age: -0.04; 95% CI, -0.6 to 0.5; P < .001; mean percentage of treatment goal weight: 10-14 vs 5-9 years of age: -8.6; 95% CI, -14.3 to -2.9; 15-18 vs 5-9 years of age: -9.8; 95% CI, -16.3 to -3.3; 15-18 vs 10-14 years of age: -1.2; 95% CI, -5.8 to 3.4; P < .001; mean heart rate (beats per min): 10-14 vs 5-9 years of age: -10; 95% CI, -21.9 to 1.9; 15-18 vs 5-9 years of age: -19.7; 95% CI, -33.1 to -6.2; 15-18 vs 10-14 years of age: -9.7; 95% CI, -18.7 to -0.7; P = .002), have higher rates of anxiety (5-9 years of age: 26.7%; 95% CI, 13.7-45.4; 10-14 years of age: 52.3%; 95% CI, 43.7%-60.7%; 15-18 years of age: 53.3%; 95% CI, 38.6%-67.5%; P = .03) and depression (5-9 years of age: 0%; 10-14 years of age: 6.8%; 95% CI, 3.6%-12.7%; 15-18 years of age: 26.7%; 95% CI, 15.7%-41.6%; P < .001), and be more likely to be hospitalized (5-9 years of age: 13.3%; 95% CI, 5.0%-31.1%; 10-14 years of age: 41.7%; 95% CI, 33.5%-50.3%; 15-18 years of age: 55.6%; 95% CI, 40.7%-69.5%; P = .001). Younger children were more likely to endorse lack of interest in food (5-9 years of age: 56.7%; 95% CI, 38.4%-73.2%; 10-14 years of age: 75.0%; 95% CI, 66.8%-81.7%; 15-18 years of age: 57.8%; 95% CI, 42.8%-71.4%; P = .03), avoidance of certain foods (5-9 years of age: 90.0%; 95% CI, 72.6%-96.8%; 10-14 years of age: 69.7%; 95% CI, 61.3%-77.0%; 15-18 years of age: 62.2%; 95% CI, 47.2%-75.3%; P = .03), and refusal based on sensory characteristics (5-9 years of age: 66.7%; 95% CI, 47.9%-81.3%; 10-14 years of age: 38.6%; 95% CI, 30.7%-47.3%; 15-18 years of age: 22.2%; 95% CI, 12.3%-36.9%; P < .001). Eating but not enough was more common in girls (75.0%; 95% CI, 64.1%-83.4%) vs boys (68.5%; 95% CI, 59.8%-76.1; P = .04), and boys had a higher rate of refusal based on sensory characteristics (51.2%; 95% CI, 40.2%-62.2%) compared with girls (31.5%; 95% CI, 23.9%-40.2%; P = .007). Conclusions and Relevance: This study suggests that ARFID is a relatively common eating disorder and is associated with important age- and sex- specific clinical characteristics that may help in early recognition and timely treatment of the presenting symptoms.

SARS-CoV-2 antibodies in Ontario health care workers during and after the first wave of the pandemic: a cohort study.

BACKGROUND: Health care workers have a critical role in the pandemic response to COVID-19 and may be at increased risk of infection. The objective of this study was to assess the seroprevalence of SARS-CoV-2 immunoglobulin G (IgG) antibodies among health care workers during and after the first wave of the pandemic. METHODS: We conducted a prospective multicentre cohort study involving health care workers in Ontario, Canada, to detect IgG antibodies against SARS-CoV-2. Blood samples and self-reported questionnaires were obtained at enrolment, at 6 weeks and at 12 weeks. A community hospital, tertiary care pediatric hospital and a combined adult-pediatric academic health centre enrolled participants from Apr. 1 to Nov. 13, 2020. Predictors of seropositivity were evaluated using a multivariable logistic regression, adjusted for clustering by hospital site. RESULTS: Among the 1062 health care workers participating, the median age was 40 years, and 834 (78.5%) were female. Overall, 57 (5.4%) were seropositive at any time point (2.5% when participants with prior infection confirmed by polymerase chain reaction testing were excluded). Seroprevalence was higher among those who had a known unprotected exposure to a patient with COVID-19 (p < 0.001) and those who had been contacted by public health because of a nonhospital exposure (p = 0.003). Providing direct care to patients with COVID-19 or working on a unit with a COVID-19 outbreak was not associated with higher seroprevalence. In multivariable logistic regression, presence of symptomatic contacts in the household was the strongest predictor of seropositivity (adjusted odds ratio 7.15, 95% confidence interval 5.42-9.41). INTERPRETATION: Health care workers exposed to household risk factors were more likely to be seropositive than those not exposed, highlighting the need to emphasize the importance of public health measures both inside and outside of the hospital.

Determinants of access to childhood cancer medicines: a comparative, mixed-methods analysis of four Caribbean countries.

BACKGROUND: Equitable access to essential medicines is a key facet of childhood cancer care, recognised by WHO as vital to improved childhood cancer outcomes globally. In the Caribbean, childhood cancer outcomes are poorer than those in most high-income countries. We aimed to generate in-depth comparative evidence of the current challenges and opportunities related to access to childhood cancer medicines in the Caribbean to identify context-sensitive health systems strategies to improve drug access and inform evidence-based paediatric cancer policies in the region. METHODS: In this convergent, parallel, mixed-methods study, we mapped and analysed the determinants of access to childhood cancer medicines in four Caribbean countries (The Bahamas, Barbados, Jamaica, and Trinidad and Tobago). We analysed contextual determinants of access to medicines within and across study site jurisdictions, alignment of childhood cancer medicine inclusion between each country's national essential medicines list (NEML) and WHO's 2017 Essential Medicines List for Children, and availability and cost of chemotherapeutic agents at five tertiary care hospitals. We used a mixed-effects logistic regression model to analyse the association of medicine price, procurement efficiency (via median price ratio [MPR]), and site with drug availability. The fixed effect evaluated the effect of site and MPR on the probability of stockout in a given month. We assessed determinants of medicine access via thematic analysis of semi-structured qualitative interviews, literature, and policy documents. FINDINGS: We collected and analysed data for 28 childhood cancer medicines from Barbados, 32 from The Bahamas, 30 from Trinidad and Tobago, and 31 from Jamaica. Despite stepwise inclusion of childhood cancer medicines in NEMLs, all four countries had frequent and recurrent stockouts for many cytotoxic medicines, showing no consistent relationship between NEML inclusion and availability. A mean MPR of greater than 3·0 in Trinidad and Tobago, The Bahamas, and Barbados suggests uniformly high procurement inefficiency, resulting in significant effects on drug stockout days. For each one unit increase in MPR the adjusted odds ratio (OR) of stockout increased by 10% (adjusted OR 1·10, 95% CI 1·04-1·16; p<0·01). These challenges in access to childhood cancer medicines stem from health system and policy dynamics at institutional, national, and supranational levels that cause price volatility and erratic medicine availability. Key challenges include disparate policy commitments (eg, among sites), inefficient procurement and supply chain management practices, and local effects of international market pressures. INTERPRETATION: The Caribbean region exemplifies deficiencies in access to childhood cancer medicines that might be overcome by improved regional harmonisation of drug registration, pharmacovigilance, and procurement alongside national forecasting to strengthen global pharmaceutical planning and prioritisation. Focused political attention to address these challenges is required to ensure efficient, reliable, and sustained availability of cancer mediciness. FUNDING: The SickKids-Caribbean Initiative.

A Novel Instrument for Endoscopic Ear Surgery With a Steerable Flexible Tip: A Pediatric Anatomical Validation Study.

HYPOTHESIS: This study compares the reaching ability of two classes of transcanal endoscopic ear surgery (TEES) instruments when operating on difficult to access anatomical targets; two novel instruments with steerable flexible tips (SFT-A and SFT-B) and suction capability are compared with standard commercially available tools. BACKGROUND: TEES surgeons identified the need for a new surgical instrument that can enable accessibility of all areas visualized by the endoscope. This motivated the development of the two instrument prototypes. METHODS: Six temporal bone models were 3D printed based on CT data from five cholesteatoma patients. Four anatomical targets were marked on each model. Using these targets, the reaching ability while using four standard TEES instruments were compared with the SFT-A and SFT-B prototypes by five surgeon participants. Results were analysed to compare success rates of contacting each target using each tool by fitting four Firth's logistic regression models. This calculated the statistically significant differences (p < 0.05) in tool success rate. RESULTS: Using SFT-A to contact the sinus tympani (100%) was significantly more successful than the Panetti suction dissector for atticus (PAT) (77%) and to contact the sinodural angle (0%) was less successful than the PAT (10%) and SFT-B (93%). Using SFT-B to contact the lateral semicircular canal (90%) was significantly more successful than all current tools and to contact the sinodural angle (93%) was significantly more successful than all tools. CONCLUSION: Using SFT-B enables enhanced accessibility of anatomical structures during TEES which may lead to less extensive bone removal to facilitate minimally invasive TEES.

Effect of the COVID-19 Pandemic on Patient Volumes, Acuity, and Outcomes in Pediatric Emergency Departments: A Nationwide Study.

OBJECTIVES: The aim of this study was to quantify the effect of the COVID-19 pandemic on pediatric emergency department (ED) utilization and outcomes. METHODS: This study is an interrupted-time-series observational study of children presenting to 11 Canadian tertiary-care pediatric EDs. Data were grouped into weeks in 3 study periods: prepandemic (January 1, 2018-January 27, 2020), peripandemic (January 28, 2020-March 10, 2020), and early pandemic (March 11, 2020-April 30, 2020). These periods were compared with the same time intervals in the 2 preceding calendar years. Primary outcomes were number of ED visits per week. The secondary outcomes were triage acuity, hospitalization, intensive care unit (ICU) admission, mortality, length of hospital stay, ED revisits, and visits for trauma and mental health concerns. RESULTS: There were 577,807 ED visits (median age, 4.5 years; 52.9% male). Relative to the prepandemic period, there was a reduction [-58%; 95% confidence interval (CI), -63% to -51%] in the number of ED visits during the early-pandemic period, with concomitant higher acuity. There was a concurrent increase in the proportion of ward [odds ratio (OR), 1.39; 95% CI, 1.32-1.45] and intensive care unit (OR, 1.20; 95% CI, 1.01-1.42) admissions, and trauma-related ED visits among children less than 10 years (OR, 1.51; 95% CI, 1.45-1.56). Mental health-related visits in children declined in the early-pandemic period (in <10 years, -60%; 95% CI, -67% to -51%; in children ≥10 years: -56%; 95% CI, -63% to -47%) relative to the pre-COVID-19 period. There were no differences in mortality or length of stay; however, ED revisits within 72 hours were reduced during the early-pandemic period (percent change: -55%; 95% CI, -61% to -49%; P < 0.001). CONCLUSIONS: After the declaration of the COVID-19 pandemic, dramatic reductions in pediatric ED visits occurred across Canada. Children seeking ED care were sicker, and there was an increase in trauma-related visits among children more than 10 years of age, whereas mental health visits declined during the early-pandemic period. When faced with a future pandemic, public health officials must consider the impact of the illness and the measures implemented on children's health and acute care needs.

Pediatric point-of-care ultrasound of optic disc elevation for increased intracranial pressure: A pilot study.

OBJECTIVE: Papilledema is often difficult to detect in children. Ocular point-of-care ultrasound (POCUS) measurement of the optic nerve sheath diameter (ONSD) is a non-invasive test for increased intracranial pressure (ICP), but no consensus exists on normal pediatric ONSD values. Detection of optic disc elevation (ODE, a component of papilledema) using POCUS has recently been qualitatively described. We sought to establish the diagnostic accuracy of different ODE cutoffs to detect increased ICP in children who underwent ocular POCUS in our pediatric emergency department (PED). METHODS: We retrospectively reviewed charts of patients ages 0-18 years who received ocular POCUS in our tertiary PED between 2011 and 2016. Patients were included if their archived POCUS examinations were deemed high-quality by a POCUS expert and they underwent ICP determination within 48 h after ocular POCUS. A blinded POCUS expert measured ODE, optic disc width at mid-height (ODWAMH), and ONSD. Receiver-operator curve analysis was performed for various cutoffs for these measurements in detecting increased ICP. RESULTS: 76 eyes from 40 patients met study criteria. 26 patients had increased ICP. The mean ODE of both eyes (ODE-B) generated the largest area under the curve (0.962, 95% CI 0.890-1). The optimal ODE-B cutoff was 0.66 mm, with a sensitivity of 96% (95% CI 79-100%) and a specificity of 93% (95% CI 79-100%). 1/40 (2.5%) of patients with ODE-B < 0.66 had increased ICP. CONCLUSIONS: ODE-B may represent the optimal ocular POCUS measurement for detecting increased ICP in children, and future prospective studies could more accurately describe the diagnostic performance of different pediatric ODE-B cutoffs.

UV, ozone, and COVID-19 transmission in Ontario, Canada using generalised linear models.

BACKGROUND: Quantifying the impact of environmental factors on COVID-19 transmission is crucial in preventing more cases. Ultraviolet (UV) radiation and ozone (O3) have reported antimicrobial properties but few studies have examined associations with community infectivity of COVID-19. Research suggests UV light can be preventative while the effect of O3 is contested. We sought to determine the relationship between UV, O3, and COVID-19 incidence in Ontario, Canada. METHODS: In our time series analyses, we calculated daily incidence rates and reproductive number (Rt) from 34,975 cases between January and June 2020 across 34 Ontario Public Health Units. We used generalised linear models, adjusting for potential confounders, to calculate point estimates (PE) and 95% confidence intervals (CI) for UV and O3. Analyses were further stratified by age groups and outbreaks at institutions versus community. RESULTS: We found that 1-week averaged UV was significantly associated with a 13% decrease (95% CI: 0.80-0.96) in overall COVID-19 Rt, per unit increase. A negative association with UV was also significant among community outbreaks (PE: 0.88, 95% CI: 0.81-0.96) but not institutional outbreaks (PE: 0.94, 95% CI: 0.85-1.03). A positive association of O3 with COVID-19 incidence is strongly suggested among institutional outbreak cases (PE: 1.06, 95% CI: 1.00-1.13). CONCLUSION: Our study found evidence to support the hypothesis that higher UV reduced transmission of COVID-19 and some evidence that ground-level O3 positively influenced COVID-19 transmission. Setting of infection should be strongly considered as a factor in future research. UV and O3 may explain some of COVID-19's seasonal behaviour.

Virtual Reality to Reduce Procedural Pain During IV Insertion in the Pediatric Emergency Department: A Pilot Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to evaluate the feasibility of using virtual reality (VR) for distraction during intravenous (IV) insertion in the pediatric emergency department (ED) and of conducting a full-scale randomized controlled trial. MATERIALS AND METHODS: Children aged 8 to 17 years old attending a tertiary care pediatric ED were randomized to interactive VR or an attention control (video on a tablet) for distraction during their IV insertion. Feasibility was determined by recruitment rates, acceptability of the intervention, response rates to outcome measures, and safety or technical problems. Satisfaction questionnaires and pain, fear, and distress scores were completed by the child, caregiver, nurse, and research assistant. Immersion in the intervention was rated by the child. Heart rate was measured. RESULTS: Children were recruited between February 2018 and May 2019. A total of 116 children were screened and 72.3% of eligible children were enrolled. Overall, 60 children were randomized to either VR (n=32) or attention control (n=28). Children, caregivers, and nurses were highly satisfied with both distraction methods. There were no significant safety, technical, or equipment issues. There was minimal disruption to clinical workflow in both groups due to study protocols. There was a clinically significant reduction in pain in the VR group. There was no significant difference in fear or distress. Children reported higher immersion in the VR environment. Heart rate increase from baseline was higher in the VR group. DISCUSSION: Our data support the feasibility of using VR for distraction during IV insertion and of conducting a full-scale randomized controlled trial. Identifying eligible patients and minimizing the number of outcome measures will be important considerations for future research.