The management of very mild and mild asthma in preschoolers, children, and adolescents.

This practice point summarizes recommendations from the Canadian Thoracic Society's 2021 "Guideline update: Diagnosis and management of asthma in preschoolers, children, and adults." New recommendations include: a decrease in the frequency of daytime symptoms and reliever use to ≤2 per week in the asthma control criteria; assessing for risk of asthma exacerbation; not using as-needed short-acting beta-agonists alone in patients at higher risk for exacerbation; and the option of as-needed budesonide/formoterol (bud/form) in those ≥12 years old if they are unable to take daily inhaled corticosteroids despite extensive asthma education and support. The preference for daily inhaled corticosteroids to manage mild asthma in children, and the recommendation against intermittent short courses of inhaled corticosteroids, are unchanged.

La prise en charge de l'asthme léger et très léger chez les enfants d'âge préscolaire, les enfants et les adolescents.

Le présent point de pratique résume la mise à jour des lignes directrices de la Société canadienne de thoracologie publiée en 2021 sur le diagnostic et la prise en charge de l'asthme chez les enfants d'âge préscolaire, les enfants et les adultes. Ces nouvelles recommandations incluent, parmi les critères de contrôle de l'asthme, une diminution de la fréquence des symptômes diurnes et de l'utilisation de médicaments pour soulager l'asthme à un maximum de deux fois par semaine. Elles comprennent également l'évaluation du risque d'exacerbation de l'asthme, la non-utilisation de bêta-agonistes à courte durée d'action seuls au besoin chez les patients à plus fort risque d'exacerbation et la possibilité d'administrer du budésonide-formotérol au besoin aux jeunes de 12 ans ou plus qui sont incapables de prendre des corticostéroïdes inhalés au quotidien malgré une éducation sur l'asthme et un soutien importants. La préférence pour la prise quotidienne de corticostéroïdes inhalés afin de traiter l'asthme léger chez les enfants et la recommandation d'éviter les courts traitements intermittents de corticostéroïdes inhalés ne changent pas.

Stratégies thérapeutiques individualisées et facteurs à considérer chez les patients atteints d'asthme léger: Discussion sur les recommandations des lignes directrices de la Société canadienne de thoracologie.

OBJECTIF: Mettre en valeur les recommandations des lignes directrices de 2021 de la Société canadienne de thoracologie (SCT) pour les adultes et les enfants de 12 ans et plus, et aborder les controverses entourant leur actualisation. SOURCES DE L'INFORMATION: Les lignes directrices de 2021 de la SCT sur l'asthme. MESSAGE PRINCIPAL: L'asthme est un problème souvent rencontré en soins primaires. Un mauvais contrôle des symptômes et les exacerbations contribuent considérablement à la morbidité. Au cours des dernières années, les lignes directrices de pratique clinique ont eu tendance à préconiser un traitement plus intense de l'asthme très léger et léger dans le but d'optimiser la maîtrise des symptômes et de réduire les exacerbations. Il faut tenir compte du risque d'exacerbations, de l'ampleur des symptômes d'asthme, des degrés d'adhésion et du coût du traitement dans le choix d'une thérapie pour les patients atteints d'un asthme très léger et léger. CONCLUSION: Cet article a pour but de passer brièvement en revue les données probantes et les justifications qui sous-tendent les options de traitement dans les lignes directrices de la SCT, pour aider les médecins à prendre des décisions centrées sur le patient.

Individualized treatment strategies and considerations in patients with mild asthma: Discussion of Canadian Thoracic Society guideline recommendations.

OBJECTIVE: To highlight recommendations from the Canadian Thoracic Society (CTS) 2021 asthma guideline for adults and children aged 12 years and older and to address controversies related to the update. SOURCES OF INFORMATION: The CTS 2021 asthma guideline. MAIN MESSAGE: Asthma is a common condition encountered in primary care. Poor symptom control and exacerbations contribute substantially to the burden of disease. Practice guidelines have been shifting in recent years toward more aggressive treatment of very mild and mild asthma, with goals of optimizing symptom control and reducing exacerbations. Consider underlying risk of exacerbation, extent of asthma symptoms, adherence levels, and treatment cost when choosing therapy for patients with very mild and mild asthma. CONCLUSION: The goal of this article is to briefly review the evidence and rationale behind treatment options in the CTS guideline to help physicians make patient-centred decisions.

Dominant negative variants in IKZF2 cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.

BACKGROUND: Helios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4+ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans. METHODS: We performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation combined with syndromic features including craniofacial differences, sensorineural hearing loss and congenital abnormalities. RESULTS: Genome sequencing revealed de novo heterozygous variants that alter the critical DNA-binding zinc fingers (ZFs) of Helios. Proband 1 had a tandem duplication of ZFs 2 and 3 in the DNA-binding domain of Helios (p.Gly136_Ser191dup) and Proband 2 had a missense variant impacting one of the key residues for specific base recognition and DNA interaction in ZF2 of Helios (p.Gly153Arg). Functional studies confirmed that both these variant proteins are expressed and that they interfere with the ability of the wild-type Helios protein to perform its canonical function-repressing IL2 transcription activity-in a dominant negative manner. CONCLUSION: This study is the first to describe dominant negative IKZF2 variants. These variants cause a novel genetic syndrome characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.

Impact of Perinatal Exposure to SARS-CoV-2 Infection on Early Health Outcomes among Infants Born from 2020 to 2021 in British Columbia, Canada.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has impacted healthcare services and outcomes. We aimed to investigate healthcare resource utilization and early health outcomes of infants born to mothers with perinatal SARS-CoV-2 infection. Methods: The study included all infants born alive between February 1, 2020, and April 30, 2021, in British Columbia. We used linked provincial population-based databases including data on COVID-19 testing, birth, and health information for up to one year from birth. Perinatal COVID-19 exposure for infants was defined being born to mothers with a positive test for SARS-CoV-2 infection during pregnancy or at delivery. Cases of COVID-19-exposed infants were matched with up to four non-exposed infants by birth month, sex, birthplace, and gestational age in weeks. Outcomes included hospitalizations, emergency department visits, and in-/outpatient diagnoses. Outcomes were compared between groups using conditional logistic regression and linear mixed effects models including effect modification by maternal residence. Results: Among 52,711 live births, 484 infants had perinatal exposure to SARS-CoV-2, an incidence rate of 9.18 per 1000 live births. Exposed infants (54.6% male) had a mean gestational age of 38.5 weeks, and 99% were born in hospital. Proportions of infants requiring at least one hospitalization (8.1% vs. 5.1%) and at least one emergency department visit (16.9% vs. 12.9%) were higher among the exposed vs. unexposed infants, respectively. Among infants from the urban area, those with exposure were more likely to have respiratory infectious diseases (odds ratio: 1.74; 95% confidence intervals: 1.07, 2.84), compared with those without exposure. Interpretation. In our cohort, infants born to mothers with SARS-CoV-2 infection have increased healthcare demands in their early infancy, which warrants further investigation.

Disparities in the Use of Teledermatology During the COVID-19 Pandemic Lockdown in a Pediatric Dermatology Practice.

Background: The COVID-19 pandemic required a rapid expansion of teledermatology services. Objective: Analyze demographic shifts in a pediatric dermatology practice session with children of color. Methods: A retrospective chart review of pediatric dermatology patients seen in the 4 practice weeks preceding the New York COVID-19 lockdown and comparable teledermatology visits during the COVID-19 pandemic lockdown. Demographic differences (e.g., race, age, gender, and household income) were analyzed. Results: A greater proportion of patients seen were White during lockdown (59.7%), compared with pre-lockdown (43.6%), with a reduction in Asian patients seen in lockdown (6.0%) compared with pre-lockdown (24.5%). A lower proportion of no-show patients (4.3%, 3/70 scheduled) were noted in lockdown compared with pre-lockdown (16%, 18/112). Preferred provider organizations (PPO) and higher-income zip codes were more common for children seen during lockdown. Limitations: The sample addresses a limited New York pediatric dermatology practice during a short time period. Conclusions: White patients and patients with PPO were more likely to access telehealth, supporting disparity in teledermatology services. These results demonstrate reduced health care access for lower-income and Asian children during the COVID-19 pandemic lockdown.

Imagining Improved Interactions: Patients' Designs To Address Implicit Bias.

Implicit biases may negatively influence healthcare providers' behaviors toward patients from historically marginalized communities, impacting providers' communication style, clinical decision-making, and delivery of quality care. Existing interventions to mitigate negative experiences of implicit biases are primarily designed to increase recognition and management of stereotypes and prejudices through provider-facing tools and resources. However, there is a gap in understanding and designing interventions from patient perspectives. We conducted seven participatory co-design workshops with 32 Black, Indigenous, People of Color (BIPOC), Lesbian, Gay, Bisexual, Transgender, Queer/Questioning (LGBTQ+), and Queer, Transgender, Black, Indigenous, People of Color (QTBIPOC) individuals to design patient-centered interventions that help them address and recover from provider implicit biases in primary care. Participants designed four types of solutions: accountability measures, real-time correction, patient enablement tools, and provider resources. These informatics interventions extend the research on implicit biases in healthcare through inclusion of valuable, firsthand patient perspectives and experiences.

Transdiagnostic Patterns of Sensory Processing in Autism and ADHD.

Sensory processing abilities are highly variable within and across people diagnosed with autism and attention-deficit/hyperactivity disorder (ADHD). This study examined the transdiagnostic nature of sensory processing abilities, and their association with features of autism and ADHD, in a large sample of autistic people (n = 495) and people with ADHD (n = 461). Five similar data-driven sensory phenotypes characterized sensory processing abilities, and showed similar patterns of association with features of autism and ADHD, across both diagnostic groups. These results demonstrate the transdiagnostic nature of sensory processing abilities, while contributing to a growing body of literature that suggests the autism and ADHD diagnostic labels have poor explanatory power.

A multi-step approach to developing a health system evaluation framework for community-based health care.

BACKGROUND: Community-based health care (CBHC) is a shift towards healthcare integration and community services closer to home. Variation in system approaches harkens the need for a conceptual framework to evaluate outcomes and impacts. We set out to develop a CBHC-specific evaluation framework in the context of a provincial ministry of health planning process in Canada. METHODS: A multi-step approach was used to develop the CBHC evaluation framework. Modified Delphi informed conceptualization and prioritization of indicators. Formative research identified evaluation framework elements (triple aim, global measures, and impact), health system levels (tiers), and potential CBHC indicators (n = 461). Two Delphi rounds were held. Round 1, panelists independently ranked indicators on CBHC relevance and health system tiering. Results were analyzed by coding agreement/disagreement frequency and central tendency measures. Round 2, a consensus meeting was used to discuss disagreement, identify Tier 1 indicators and concepts, and define indicators not relevant to CBHC (Tier 4). Post-Delphi, indicators and concepts were refined, Tier 1 concepts mapped to the evaluation framework, and indicator narratives developed. Three stakeholder consultations (scientific, government, and public/patient communities) were held for endorsement and recommendation. RESULTS: Round 1 Delphi results showed agreement for 300 and disagreement for 161 indicators. Round 2 consensus resulted in 103 top tier indicators (Tier 1 = 19, Tier 2 = 84), 358 bottom Tier 3 and 4 indicators, non-CBHC measure definitions, and eight Tier 1 indicator concepts-Mortality/Suicide; Quality of Life, and Patient Reported Outcome Measures; Global Patient Reported Experience Measures; Cost of Care, Access to Integrated Primary Care; Avoidable Emergency Department Use; Avoidable Hospitalization; and E-health Penetration. Post Delphi results refined Tier 3 (n = 289) and 4 (n = 69) indicators, and identified 18 Tier 2 and 3 concepts. When mapped to the evaluation framework, Tier 1 concepts showed full coverage across the elements. 'Indicator narratives' depicted systemness and integration for evaluating CBHC. Stakeholder consultations affirmed endorsement of the approach and evaluation framework; refined concepts; and provided key considerations to further operationalize and contextualize indicators, and evaluate CBHC as a health system approach. CONCLUSIONS: This research produced a novel evaluation framework to conceptualize and evaluate CBHC initiatives. The evaluation framework revealed the importance of a health system approach for evaluating CBHC.

Asthma in the Americas: An Update: A Joint Perspective from the Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, and American Thoracic Society.

Asthma affects a large number of people living in the Americas, a vast and diverse geographic region comprising 35 nations in the Caribbean and North, Central, and South America. The marked variability in the prevalence, morbidity, and mortality from asthma across and within nations in the Americas offers a unique opportunity to improve our understanding of the risk factors and management of asthma phenotypes and endotypes in children and adults. Moreover, a better assessment of the causes and treatment of asthma in less economically developed regions in the Americas would help diagnose and treat individuals migrating from those areas to Canada and the United States. In this focused review, we first assess the epidemiology of asthma, review known and potential risk factors, and examine commonalities and differences in asthma management across the Americas. We then discuss future directions in research and health policies to improve the prevention, diagnosis, and management of pediatric and adult asthma in the Americas, including standardized and periodic assessment of asthma burden across the region; large-scale longitudinal studies including omics and comprehensive environmental data on racially and ethnically diverse populations; and dissemination and implementation of guidelines for asthma management across the spectrum of disease severity. New initiatives should recognize differences in socioeconomic development and health care systems across the region while paying particular attention to novel or more impactful risk factors for asthma in the Americas, including indoor pollutants such as biomass fuel, tobacco use, infectious agents and the microbiome, and psychosocial stressor and chronic stress.

Juvenile Dermatomyositis and Acute Respiratory Failure in a Teen.

CASE PRESENTATION: A 17-year-old previously healthy Taiwanese girl presented with syncope on a background of 1 month of weakness, polyarthritis, and heliotrope rash. Her presentation and investigations, which included an elevated creatine phosphokinase level and diffuse myositis on lower limb MRI, were consistent with juvenile dermatomyositis (JDM).

Dornase alfa for cystic fibrosis.

BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. OBJECTIVES: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 12 October 2020. Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 08 February 2021. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. DATA COLLECTION AND ANALYSIS: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence. MAIN RESULTS: The searches identified 74 trials, of which 19 (2565 participants) met our inclusion criteria. 15 trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years. Dornase alfa compared to placebo or no treatment Dornase alfa probably improved forced expiratory volume at one second (FEV1) at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed treatment may make little or no difference  in quality of life. Dornase alfa probably reduced the number of pulmonary exacerbations in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs. Dornase alfa: daily versus alternate day One cross-over trial (43 children) found little or no difference between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence). Dornase alfa compared to other medications that improve airway clearance Results for these comparisons were mixed. One trial (43 children) showed dornase alfa may lead to a greater improvement in FEV1 compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported little or no differences in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found dornase alfa may improve quality of life compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found little or no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence). When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is evidence to show that, compared with placebo, therapy with dornase alfa may improve lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer, probably due to treatment. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.

Factors influencing clinical trial participation for adult and pediatric patients with cystic fibrosis.

There remains a limited understanding of the factors influencing clinical trial participation for individuals with Cystic Fibrosis (CF). A comprehensive survey was developed to examine the interests, preferences, and barriers/facilitators to research and clinical trial participation for CF patients. A consecutive sample of 198 CF adults attending the St. Paul's Hospital CF Clinic and parents of children with CF attending the BC Children's Hospital CF Clinic from Vancouver, Canada were surveyed. Parents of pediatric patients were less comfortable with blood collection, required more safety data prior to participating, and were more concerned about potential side effects. Very few respondents (<10%) appeared able/willing to fulfill the typical requirements to participate in a phase 1 clinical trial. Overall, there were more similarities than differences between the responses of adult and parents of pediatric CF patients. The patient-centered information can be used to inform the design of future clinical trials to enhance feasibility.