Does celecoxib prescription for pain management impact post-tonsillectomy hemorrhage requiring surgery? A retrospective observational cohort study.

BACKGROUND: Adenotonsillectomy and tonsillectomy (now referred to as tonsillectomy thereafter) are common pediatric surgeries. Postoperative complications include hemorrhage requiring surgery (2-3% of cases) and pain. While non-steroidal anti-inflammatory drugs are commonly administered for post-surgical pain, controversy exists regarding bleeding risk with cyclo-oxygenase-1 inhibition and associated platelet dysfunction. Preliminary evidence suggests selective cyclo-oxygenase-2 inhibitors, for example celecoxib, effectively manage pain without adverse events including bleeding. Given the paucity of data for routine celecoxib use after tonsillectomy, we investigated the association between post-operative celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery using chart-review data from the Children's Hospital of Eastern Ontario, Canada. METHODS: After ethics approval we performed a retrospective single-center observational cohort study in children <18 yrs 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 6468 was identified and 5846 children with complete data were included in analyses. Median (interquartile range) age was 6.10 (4.40, 9.00) years and 46% were female. In our cohort, 28.1% (n=1644) were prescribed celecoxib. Among the 4996 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% (30/1548; 95% CI: 1.36-2.75) and 1.62% (56/3448; 95% CI: 1.25-2.10), respectively. Modelling did not identify an association between celecoxib prescription and increased odds of post-tonsillectomy hemorrhage requiring surgery (OR=1.4, 95% CI: 0.85-2.31, 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 multi-site randomized controlled trial.

Factors associated with future hospitalization among children with asthma: a systematic review.

OBJECTIVE: Asthma is a leading cause of emergency department (ED) visits and hospitalizations in children, though many could be prevented. Our study objective was to identify factors from the published literature that are associated with future hospitalization for asthma beyond 30 days following an initial asthma ED visit. DATA SOURCES: We searched CINAHL, CENTRAL, MEDLINE, and Embase for all studies examining factors associated with asthma-related hospitalization in children from January 1, 1992 to February 7, 2022.Selecting Studies: All citations were reviewed independently by two reviewers and studies meeting inclusion criteria were assessed for risk of bias. Data on all reported variables were extracted from full text and categorized according to identified themes. Where possible, data were pooled for meta-analysis using random effects models. RESULTS: Of 2262 studies, 68 met inclusion criteria. We identified 28 risk factors and categorized these into six themes. Factors independently associated with future hospitalization in meta-analysis include: exposure to environmental tobacco smoke (OR = 1.94 95%CI 0.67-5.61), pets exposure (OR = 1.67 95%CI 1.17-2.37), and previous asthma hospitalizations (OR = 3.47 95% CI 2.95-4.07). Additional related factors included previous acute care visits, comorbid health conditions (including atopy), allergen exposure, severe-persistent asthma phenotype, inhaled steroid use prior to ED visit, poor asthma control, higher severity symptoms at ED presentation, warmer season at admission, longer length of stay or ICU admission, and African-American race/ethnicity. CONCLUSIONS: We identified multiple factors that are consistently associated with future asthma hospitalization in children and could be used to identify those who would benefit from targeted preventative interventions.

Hot spots for pediatric asthma emergency department visits in Ottawa, Canada.

OBJECTIVE: Pediatric asthma emergency department (ED) visits and repeat visits place a substantial burden on healthcare. National and provincial level studies demonstrate geographic variation in asthma ED visits and links to marginalization, but preclude translation into practical targeting of healthcare delivery. It is important to understand the relationship between pediatric asthma ED visits and marginalization at a more granular level. To map the city-level geographic variation in pediatric asthma ED visit and re-visit rates at the Children's Hospital of Eastern Ontario (CHEO) in Ottawa, Canada and the relationship with marginalization. METHODS: We performed a single center retrospective cohort study of children ages 1-17 with one or more ED visits for asthma at the CHEO in Ottawa. Using postal codes, we linked patients to census tracts. Per census tract, we mapped pediatric asthma ED visit and re-visit rates within one year and identified overlap with the Ontario Marginalization Index. RESULTS: Of 1,620 children with an index ED visit, 18.5% had a repeat ED visit. We identified 10 hot spot census tracts each for pediatric asthma ED visit and re-visit rates. We identified an overlap between urban hot spots and areas with high ethnic concentration or low dependency. CONCLUSION: At a granular, city-wide level, pediatric asthma ED visit and re-visit rates are heterogeneous. Urban hot spots, in contrast to rural, have more overlap with marginalization, especially ethnic concentration. These methods can be used in other jurisdictions to inform practical community strategies for geographically-targeted prevention of pediatric asthma-related ED visits in vulnerable areas.Abbreviations:ED:Emergency department;CHEO:Children's Hospital of Eastern Ontario;PRAM:Pediatric Respiratory Assessment Measure;ON-Marg:Ontario Marginalization Index;SES:Socioeconomic status;US:United States.Supplemental data for this article can be accessed at publisher's website.

Predictors of future acute asthma visits among children receiving guideline recommended emergency department discharge management.

BACKGROUND: Asthma emergency department (ED) visits remain frequent among children, prompting ongoing pursuit of preventative strategies. OBJECTIVE: We identified factors associated with future acute asthma ED visits among children who had already received guideline recommended discharge management following a prior asthma ED visit. METHODS: We performed a retrospective cohort study of children ages 1-17 years with a first asthma ED visit to the Children's Hospital of Eastern Ontario in Canada between September 2014-August 2015. Children who received recommended discharge management including an inhaled corticosteroids prescription and/or an asthma action plan were included. We used multivariable logistic regression to identify factors associated with a future acute asthma visits one year following the first ED visit. RESULTS: Among 909 children with a first asthma ED visit, 24% had a future acute asthma visit within one year. Future acute asthma visits were more likely in children with a nut/peanut allergy (OR 1.76, 95% CI: 1.15, 2.70), higher severity symptoms (OR 2.04, 95% CI: 1.23, 3.39), a primary care physician (OR 2.23, 95% CI: 1.26, 3.93), or a prior diagnosis of asthma (OR 1.53, 95% CI: 1.03, 2.28). CONCLUSION: Children at risk for repeat acute asthma ED visits despite having a primary care provider and receiving recommended discharge management at their first ED visit can be identified by factors such as having a nut/peanut allergy, a prior asthma diagnosis, and higher severity symptoms at ED presentation. These factors can be used to target more intensive preventative interventions to those most in need.

The association between climate, geography and respiratory syncitial virus hospitalizations among children in Ontario, Canada: a population-based study.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization. METHODS: We conducted a population-based nested case-control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors. RESULTS: We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR = 0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR = 1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR = 1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR = 1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR = 1.34, 95%CI: 1.26, 1.41). CONCLUSIONS: In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.

Emergency department visit count: a practical tool to predict asthma hospitalization in children.

Objectives: Resource limitations and low rates of follow-up with primary care providers currently limit the impact of emergency department (ED)-based preventative strategies for children with asthma. A mechanism to recognize the children at highest risk of future hospitalization is needed to target comprehensive preventative interventions at discharge. The primary objective of this study was to determine whether frequency of ED visits predicts future asthma hospitalization in children.Methods: Children aged 2-16.99 years with asthma ED visits between 2012 and 2015 were identified through health administrative data. Survival analysis using Kaplan-Meier estimator and multivariable Cox regression models with time-varying covariates were used to quantify the number of ED visits in the previous year that would best predict hospitalization risk in the following year, after adjustment for age, sex, and presentation severity.Results: We identified 2669 patients with 3300 asthma ED visits. ED visit count was an independent predictor of future hospitalization risk (p < 0.001), demonstrating a dose-dependent response. Compared with zero previous visits, the adjusted hazard of future hospitalization in children with one visit or two or more visits was 2.9 (95% CI 1.6-5.0) and 4.4 (95% CI 1.9-10.4), respectively.Conclusions: ED visit count is a reliable predictor of future asthma hospitalization risk. Future studies could aim to validate these findings to support using ED visit count as a practical and objective tool to predict the children at the highest risk of future hospitalization and therefore, those who may benefit most from ED-based preventative interventions.

The influence of prenatal mental health service use on the incidence of childhood asthma: a population-based cohort study.

OBJECTIVES: We aimed to determine whether maternal mental health service use during pregnancy, a potential proxy measure of prenatal maternal stress, is associated with the development of asthma in a large population-based sample of children. We hypothesized that children born to mothers with mental health service use during pregnancy would have a higher incidence of childhood asthma. STUDY DESIGN: Health administrative data from Ontario, Canada (population >13 million) was used to identify pairs of mothers linked with their children born between April 1, 2001 to March 31, 2002. Descriptive statistics were used to compare the cumulative incidence of asthma by age 12 years in children whose mothers did or did not have prenatal mental health service use. Multivariable logistic regression was used to estimate the association between prenatal maternal mental health service use and childhood asthma incidence, after adjusting for the child's sex, residency (rural vs. urban), socioeconomic status, comorbid health conditions, low birthweight, and maternal history of asthma. RESULTS: In a population-based sample of 122,333 children, those born to mothers with mental health service use during pregnancy had increased odds of developing asthma (odds ratio: 1.16, 95% confidence intervals: 1.12, 1.20, p < 0.001). CONCLUSIONS: Prenatal maternal mental health service use is an independent risk factor for the development of asthma in childhood. This supports growing evidence for the importance of in utero exposure to maternal stress factors in asthma pathogenesis. This study highlights a potential strategy for the primary prevention of childhood asthma, namely improved recognition and management of mental health issues and stress in pregnant mothers.

Trends in the age of diagnosis of childhood asthma.

BACKGROUND: The cause of rising asthma incidence over time remains unexplained. Examining trends in the age of diagnosis across successive birth cohorts may offer insights into asthma etiology. OBJECTIVE: To examine trends in the age at asthma diagnosis and the age and proportion of children hospitalized at first asthma diagnosis in Ontario, Canada. METHODS: Eight consecutive birth cohorts of children (1993-2000) were observed using administrative data from a universal health insurance plan in Ontario, Canada (population 13 million). Trends in the need for hospitalization and age at asthma diagnosis were examined with descriptive and survival analyses. RESULTS: The records of 1,059,511 children were examined, of whom 201,958 developed asthma in the first 8 years of life, with an average cumulative incidence of 19.1%. Mean age at asthma diagnosis decreased from 4.7 ± 1.5 years in birth year 1993 to 2.6 ± 2.0 years in birth year 2000 (P < .0001), with a higher adjusted risk of asthma diagnosis (hazard ratio, 6.7; 95% CI, 6.5-6.9) in the first 3 years of life for children born after 1996 versus children born in the period 1993 to 1995 (hazard ratio, 1.4; 95% CI, 1.3-1.4). The proportion of children hospitalized at asthma diagnosis stayed stable while the age at first asthma hospitalization decreased over time (P < .0001). CONCLUSIONS: This study demonstrates a significant increase in asthma incidence and a decrease in the age of asthma diagnosis across multiple birth cohorts. Changes in asthma incidence over time are primarily explained by variations in asthma rates in children younger than 3 years.

Diagnosis and management of asthma in preschoolers: A Canadian Thoracic Society and Canadian Paediatric Society position paper.

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥8 days/month) asthma-like symptoms or recurrent (≥2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified.

L'asthme fait souvent son apparition avant l'âge de six ans. Cependant, il subsiste des incertitudes relativement à quand et comment un enfant d'âge préscolaire ayant des symptômes de type asthmatique peut être diagnostiqué avec cette condition. Ceci retarde le traitement et contribue à la morbidité à court et à long terme. L'Assemblée clinique sur l'asthme de la Société canadienne de thoracologie s'est associée à la Société canadienne de pédiatrie pour créer un groupe de travail conjoint afin de préparer un document de principes sur le diagnostic et la prise en charge de l'asthme chez les enfants d'âge préscolaire. En l'absence de mesures de la fonction pulmonaire, le diagnostic d'asthme devrait être envisagé chez les enfants de un à cinq ans ayant des symptômes de type asthmatique fréquents (≥8 jours/mois) ou des exacerbations récurrentes (≥2) (épisodes accompagnés de signes compatibles). Le diagnostic nécessite une documentation objective des signes cliniques ou un compte rendu parental convaincant de symptômes d'obstruction des voies respiratoires et de réversibilité de l' obstruction (amélioration suite à un traitement pour l'asthme), ainsi que l'absence de suspicion clinique de tout autre diagnostic. La respiration sifflante, souvent accompagnée de difficultés respiratoires et de toux, est le signe cardinal de l'obstruction des voies respiratoires. La réversibilité à la suite de la prise de médicaments pour l'asthme se définie par l'observation directe par un professionnel de la santé compétent, d'une amélioration après l'administration de ß2-agonistes à courte durée d'action (BACA) (accompagnés ou non de corticostéroïdes par voie orale) pendant une exacerbation aigue (méthode diagnostique privilégiée). Cependant, chez les enfants qui n'ont pas à l'examen une respiration sifflante (ni d'autres signes d'obstruction des voies respiratoires), la réversibilité peut être déterminée par un compte rendu parental convaincant d'une réponse symptomatique à un essai thérapeutique de trois mois de corticostéroïdes inhalés, à dose moyenne, avec un BACA au besoin (méthode diagnostique alternative), ou avec seulement un BACA au besoin (méthode diagnostique alternative moins certaine) est recommandé. Les auteurs présentent des messages clés quant aux enfants chez lesquels on doit envisager le diagnostic, quant aux termes désuets à abandonner, quant aux situations pour lesquelles on doit orienter l'enfant vers un spécialiste de l'asthme et quant à la stratégie de prise en charge initiale. Enfin, ils décrivent la stratégie de diffusion de ces messages et identifient les domaines de recherche prioritaires.

A real-world evaluation of the effectiveness and Sufficiency of Current Emergency Department Preventative Strategies for Reducing Emergency Department revisits in a Canadian children's hospital: a retrospective cohort study.

BACKGROUND: Despite asthma guidelines' recommended emergency department preventative strategies (EDPS), repeat asthma-related emergency department (ED) visits remain frequent. METHODS: We performed a retrospective cohort study of children aged 1-17 years presenting with asthma to the Children's Hospital of Eastern Ontario (CHEO) ED between September 1, 2014 - August 31, 2015. EDPS was defined as provision of education on trigger avoidance and medication technique plus documentation of an asthma action plan, a prescription for an inhaled controller medication or referral to a specialist. Logistic regression was used to identify factors associated with receipt of EDPS. We further compared the odds of repeat presentation to the ED within the following year among children who had received EDPS versus those who had not. RESULTS: 1301 patients were included, and the mean age of those who received EDPS was 5.0 years (SD = 3.7). Those with a moderate (OR = 3.67, 95% CI: 2.49, 5.52) to severe (OR = 3.69, 95% CI: 2.50, 5.45) asthma presentation were most likely to receive EDPS. Receiving EDPS did not significantly reduce the adjusted odds of repeat ED visits, (OR = 0.82, 95% CI: 0.56, 1.18, p = 0.28). CONCLUSIONS: Patients with higher severity asthma presentations to the ED were more likely to receive EDPS, but this did not appear to significantly decrease the proportion with a repeat asthma ED visit. These findings suggest that receipt of EDPS in the ED may not be sufficient to prevent repeat asthma ED visits in all children.

Adaptive Mentoring Networks and Compassionate Care: A Qualitative Exploration of Mentorship for Chronic Pain, Substance Use Disorders and Mental Health.

This study undertook an exploration of how Adaptive Mentoring Networks focusing on chronic pain, substance use disorders and mental health were supporting primary care providers to engage in compassionate care. The study utilised the Cole-King & Gilbert Compassionate Care Framework to guide qualitative semi-structured interviews of participants in two Adaptive Mentoring Networks in Ontario, Canada. Fourteen physician participants were interviewed including five mentors (psychiatrists) and nine mentees (family physicians) in the Networks. The Cole-King & Gilbert Framework helped provide specific insights on how these mentoring networks were affecting the attributes of compassion such as motivation, distress-tolerance, non-judgement, empathy, sympathy, and sensitivity. The findings of this study focused on the role of compassionate provider communities and the development of skills and attitudes related to compassion that were both being supported in these networks. Adaptive Mentoring Networks can support primary care providers to offer compassionate care to patients with chronic pain, substance use disorders, and mental health challenges. This study also highlights how these networks had an impact on provider resiliency, and compassion fatigue. There is promising evidence these networks can support the "quadruple aim" for healthcare systems (improve patient and provider experience, health of populations and value for money) and play a role in addressing the healthcare provider burnout and associated health workforce crisis.

Obstructive Sleep Apnea and Mental Health Disorders in the Pediatric Population: A Retrospective Population-based Cohort Study.

RATIONALE: Information is limited about the association between obstructive sleep apnea (OSA) and mental disorders in children. OBJECTIVES: In children, (1) to evaluate the association between OSA and new mental healthcare encounters; (2) to compare mental healthcare encounters two years post- to pre-OSA treatment initiation. METHODS: We conducted a retrospective longitudinal cohort study using Ontario health administrative data (Canada). Children (0-18 years) who underwent diagnostic polysomnography (PSG) 2009-2016 and met criteria for definition of moderate-severe OSA (PSG-OSA) were propensity score weighted by baseline characteristics and compared to children who underwent a PSG in the same period but did not meet the OSA definition (PSG-No-OSA). Children were followed until March 2021. Weighted cause-specific Cox Proportional Hazards and Modified Poisson regression models were used to compare time from PSG to first mental healthcare encounter and frequency of new mental healthcare encounters per person time, respectively. Among those who underwent adenotonsillectomy (AT) or were prescribed and claimed positive airway pressure therapy (PAP), we used age-adjusted conditional logistic regression models to compare two years post- to pre-treatment odds of mental healthcare encounters. RESULTS: Of 32,791 children analyzed, 7,724 (23.6%) children met criteria for moderate-severe OSA. In PSG-OSA group, 7,080 (91.7%) were treated (AT or PAP). Compared to PSG-No-OSA, the PSG-OSA group had a shorter time from PSG to first mental healthcare encounter (HR: 1.08; 95%CI: 1.05-1.12), but less frequent mental healthcare encounters in follow-up (RR: 0.92; 95% CI: 0.87-0.97). OSA treatment (AT or PAP) was associated with lower odds of mental healthcare encounters two years post-treatment initiation compared to two years prior (OR: 0.69; 95% CI: 0.65-0.74). CONCLUSION: In this large population-based study of children who underwent PSG for sleep disorder assessment, OSA diagnosis/treatment was associated with an improvement in some mental health indicators, such as fewer new mental healthcare encounters compared to no OSA, and lower odds of mental healthcare encounters compared to pre-OSA treatment.

A longitudinal analysis of early lung function trajectory in survivors of childhood Hodgkin lymphoma.

BACKGROUND: Childhood Hodgkin lymphoma survivors suffer from long-term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%. AIMS: This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy. METHODS AND RESULTS: In this single-center, 20-year retrospective cohort study, we included patients who were <18 years old at diagnosis of Hodgkin lymphoma between January 1994 and December 2014, and received bleomycin or thoracic radiation. We measured pulmonary function and reported on percent predicted values for forced expiratory volume in 1 s, total lung capacity, and diffusing capacity of the lungs. We used linear mixed models to identify the association of clinical factors with longitudinal changes in lung function at time points before and after treatment completion. Of 80 children who met inclusion criteria, all were treated with bleomycin, and 83.8% received thoracic radiation. More than half (51.2%) of patients had any abnormalities in lung function measures during the study observation period which averaged 24.2 months (±31.1SD). Females, younger age at diagnosis and treatment with radiation were associated with lower lung function measurements at various time points. While the majority of children experienced a recovery of their lung function within 1-2 years after treatment completion, some children with these risk factors did not. CONCLUSION: Pulmonary function abnormalities begin early in children treated for Hodgkin lymphoma. While the majority of children demonstrate a slow and continuous improvement in lung function back to baseline over time, we recommend routine asymptomatic screening of pulmonary function in certain childhood cancer survivors, particularly females, those diagnosed young and patients who received radiation therapy.

Evaluating the Utility and Privacy of Synthetic Breast Cancer Clinical Trial Data Sets.

PURPOSE: There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques. METHODS: We synthesized data sets from eight breast cancer clinical trial data sets using three types of generative models: sequential synthesis, conditional generative adversarial network, and variational autoencoder. Synthetic data utility was evaluated by replicating the published analyses on the synthetic data and assessing concordance of effect estimates and CIs between real and synthetic data. Privacy was evaluated by measuring attribution disclosure risk and membership disclosure risk. RESULTS: Utility was highest using the sequential synthesis method where all results were replicable and the CI overlap most similar or higher for seven of eight data sets. Both types of privacy risks were low across all three types of generative models. DISCUSSION: Synthetic data using sequential synthesis methods can act as a proxy for real clinical trial data sets, and simultaneously have low privacy risks. This type of generative model can be one way to enable broader sharing of clinical trial data.

Lower airway nitric oxide is increased in children with sickle cell disease.

OBJECTIVES: To determine alveolar and airways nitric oxide (NO) levels in children with sickle cell disease (SCD). STUDY DESIGN: Multiple flows fractional exhaled NO (FE(NO)), bronchial NO flux (J'aw(NO)), and alveolar NO concentration (Ca(NO)) were determined prospectively in 16 non-atopic children with SCD in a tertiary ambulatory clinic and compared with those in 10 children with primary ciliary dyskinesia and 22 healthy control subjects. Differences in FE(NO), J'aw(NO), and Ca(NO) were compared with mixed model analysis and Mann-Whitney tests. RESULTS: Children with SCD had reference range FE(NO) at 50 mL/sec, but FE(NO) was elevated across all flows compared with healthy control subjects (mean difference=2.10±0.91 parts per billion, P=.03). Subjects with SCD had increased J'aw(NO) (1177±533 picoliters per second versus 833±343 picolitres per second, P=.03), and Ca(NO) was no different from control subjects. In contrast, children with primary ciliary dyskinesia had decreased FE(NO) (mean difference=3.36±1.24 parts per billion, P<.01) and J'aw(NO) (507±259 picoliters per second versus 833±343 picoliters per second, P<.01). CONCLUSIONS: Lower airways NO is increased in children with SCD. Elevation of J'aw(NO) may represent dysregulation of NO metabolism or subclinical airways inflammation.

Optimizing pediatric asthma education using virtual platforms during the COVID-19 pandemic.

BACKGROUND: We compared patient and caregiver knowledge and confidence for managing asthma, and participant experiences when comprehensive asthma education was delivered in person versus in the virtual setting. METHODS: We performed a multi-methods study using structured surveys and qualitative interviews to solicit feedback from patients and caregivers following participation in a comprehensive asthma education session between April 2018 and October 2021. We compared participant knowledge and confidence for managing asthma as well as user experience when the education was attended in-person or virtually. Quantitative responses were summarized descriptively, and qualitative feedback was analyzed for major themes. RESULTS: Of 100 caregivers/patients who completed post education satisfaction surveys and interviews, 52 attended in person and 48 virtually, with the mean age of patients being 6.7 years (range: 1.2-17.0). Participant reported gains in knowledge and confidence for asthma management were not different between groups and 65.2% preferred attending virtual asthma education. The majority of participants described virtual education as a safer modality that was more convenient and accessible. CONCLUSIONS: We demonstrated the successful implementation of a novel, virtual asthma education program for patients and caregivers of children with asthma. Both virtual and in-person delivered asthma education were equally effective for improving perceived knowledge and confidence for asthma self-management and virtual education was considered safer, more convenient and accessible. Virtual asthma education offers an attractive and effective option for improving the reach of quality asthma education programs and may allow more children/patients to benefit.

Clinical predictors of nonadherence to positive airway pressure therapy in children: a retrospective cohort study.

STUDY OBJECTIVES: Despite the importance of treating sleep-disordered breathing, positive airway pressure adherence rates in children are low. Identifying readily available predictors of nonadherence would enable the development of targeted interventions and supports, but literature is limited. Our objective was to identify baseline clinical predictors of 6-month positive airway pressure therapy nonadherence in children with SDB through a retrospective cohort study. METHODS: This study evaluated children (ages 8-17 years) prescribed positive airway pressure therapy for sleep-disordered breathing between 2011 and 2017 at a single pediatric tertiary hospital. The primary outcome was nonadherence at 6 months, measured using both machine downloads and self-report. Candidate baseline predictors included demographics, comorbidities, and sleep-disordered breathing characteristics. Relative risks (RR) and 95% confidence intervals (CI) were estimated using a modified Poisson regression. Missing data were imputed prior to analysis. RESULTS: The study included 104 children. The independent predictors most strongly associated with greater nonadherence were older age (RR = 1.08 for a 1-year increase; 95% CI, 1.00-1.16) and higher oxygen saturation nadir (RR = 1.03 for a 1% increase; 95% CI, 1.00-1.05), whereas those most strongly associated with lower nonadherence were higher arousal index (RR = 0.97 for a 1 event/h increase; 95% CI, 0.95-1.00), developmental delay (RR = 0.58; 95% CI, 0.30-1.13), and asthma (RR = 0.72; 95% CI, 0.44-1.17). CONCLUSIONS: Overall, children who are older, have less-severe sleep-disordered breathing, or less-disrupted sleep at baseline are more likely to be nonadherent to positive airway pressure therapy and may benefit from additional supports to acclimatize to therapy. As clinical predictors were only weakly associated with nonadherence, nonclinical characteristics may play a larger role in predicting adherence.

Comparison of childhood asthma incidence in 3 neighbouring cities in southwestern Ontario: a 25-year longitudinal cohort study.

BACKGROUND: Air pollution is a known trigger for exacerbations among individuals with asthma, but its role in the development of new-onset asthma is unclear. We compared the rate of new asthma cases in Sarnia, a city with high pollution levels, with the rates in 2 neighbouring regions in southwestern Ontario, Canada. METHODS: Using a population-based birth cohort design and linked health administrative data, we compared the hazard of incident asthma among children 0 to 10 years of age between those born in Lambton (Sarnia) and those born in Windsor and London-Middlesex, for the period Apr. 1, 1993, to Mar. 31, 2009. We used Cox proportional hazards models to adjust for year of birth and exposure to air pollutants (nitrogen dioxide, sulphur dioxide [SO2], ozone and small particulate matter [PM2.5]), as well as maternal, geographic and socioeconomic factors. RESULTS: Among 114 427 children, the highest incidence of asthma was in Lambton, followed by Windsor and London-Middlesex (30.3, 24.4 and 19.8 per 1000 person-years, respectively; p < 0.001). Relative to Lambton, the hazard of asthma, adjusted for socioeconomic and perinatal factors, was lower in Windsor (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.67-0.77) and London-Middlesex (HR 0.65, 95% CI 0.61-0.69). Inclusion of air pollutants attenuated this relative difference in both Windsor (HR 0.79, 95% CI 0.62-1.01) and London-Middlesex (HR 0.89, 95% CI 0.64-1.24). INTERPRETATION: We identified a higher incidence of asthma among children born in Lambton (Sarnia) relative to 2 other regions in southwestern Ontario. Higher levels of air pollution (particularly SO2 and PM2.5) in this region, as experienced by children in their first year of life, may be contributory.

Risk of asthma in children diagnosed with bronchiolitis during infancy: protocol of a longitudinal cohort study linking emergency department-based clinical data to provincial health administrative databases.

INTRODUCTION: The Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) and the Bronchiolitis Severity Cohort (BSC) study enrolled infants with bronchiolitis during the first year of life. The CanBEST trial suggested that treatment of infants with a combined therapy of high-dose corticosteroids and nebulised epinephrine reduced the risk of admission to hospital. Our study aims to-(1) quantify the risk of developing asthma by age 5 and 10 years in children treated with high-dose corticosteroid and epinephrine for bronchiolitis during infancy, (2) identify risk factors associated with development of asthma in children with bronchiolitis during infancy, (3) develop asthma prediction models for children diagnosed with bronchiolitis during infancy. METHODS AND ANALYSIS: We propose a longitudinal cohort study in which we will link data from the CanBEST and BSC study with routinely collected data from provincial health administrative databases. Our outcome is asthma incidence measured using a validated health administrative data algorithm. Primary exposure will be treatment with a combined therapy of high-dose corticosteroids and nebulised epinephrine for bronchiolitis. Covariates will include type of viral pathogen, disease severity, medication use, maternal, prenatal, postnatal and demographic factors and variables related to health service utilisation for acute lower respiratory tract infection. The risk associated with development of asthma in children treated with high-dose corticosteroid and epinephrine for bronchiolitis will be assessed using multivariable Cox proportional hazards regression models. Prediction models will be developed using multivariable logistic regression analysis and internally validated using a bootstrap approach. ETHICS AND DISSEMINATION: Our study has been approved by the ethics board of all four participating sites of the CanBEST and BSC study. Finding of the study will be disseminated to the academic community and relevant stakeholders through conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN56745572; Post-results.

Predictors of Hospitalization for Children With Croup, a Population-Based Cohort Study.

OBJECTIVES: We sought to determine predictors of hospitalization for children presenting with croup to emergency departments (EDs), as well as predictors of repeat ED presentation and of hospital readmissions within 18 months of index admission. We also aimed to develop a practical tool to predict hospitalization risk upon ED presentation. METHODS: Multiple deterministically linked health administrative data sets from Ontario, Canada, were used to conduct this population-based cohort study between April 1, 2006 and March 31, 2017. Children born between April 1, 2006, and March 31, 2011, were eligible if they had 1 ED visit with a croup diagnosis. Multivariable logistic regression was used to determine factors associated with hospitalization, subsequent ED visits, and subsequent croup hospitalizations. A multivariable prediction tool and associated scoring system were created to predict hospitalization risk within 7 days of ED presentation. RESULTS: Overall, 1811 (3.3%) of the 54 981 eligible children who presented to an Ontario ED were hospitalized. Significant hospitalization predictors included age, sex, Canadian Triage and Acuity Scale score, gestational age at birth, and newborn distress. Younger patients and boys were more likely to revisit the ED for croup. Our multivariable prediction tool could forecast hospitalization up to a 32% probability for a given patient. CONCLUSIONS: This study is the first population-based study in which predictors of hospitalization for croup based on demographic and historical factors are identified. Our prediction tool emphasized the importance of symptom severity on ED presentation but will require refinement before clinical implementation.