Integration of Family Navigation into ECHO Autism for Pediatric Primary Care in Underserved Communities.

Children with autism from underserved communities face complex system-, provider-, and family-level barriers to accessing timely diagnosis and early intervention. The current study evaluated the preliminary effects and feasibility of a new program (ECHO Autism LINKS) that integrated pediatric primary care provider (PCP) training with family navigation (FN) to bridge the gaps between screening, referral, and service access. Three cohorts of PCPs (n = 42) participated in the program, which consisted of 60-minute sessions delivered by Zoom twice per month for 12 months. Each session included didactics, case-based learning, and collaborative discussion with participants and an interdisciplinary team of experts. Family navigators were members of the expert team and provided FN services to families referred by PCP participants. Program attendance and engagement were strong, with 40 cases presented and 258 families referred for FN services, most of whom (83%) needed help accessing and connecting with services, and 13% required ongoing support due to complex needs. PCPs demonstrated significant improvements in self-efficacy in providing best-practice care for children with autism, reported high satisfaction, and observed improved knowledge and practice as a result of the program. The results of this initial pilot provide support for the feasibility, acceptability, and preliminary efficacy of the ECHO Autism LINKS program. The model holds promise in addressing complex barriers to healthcare access by providing both PCPs and families with the knowledge and support they need. Future research is needed to evaluate the efficacy and effectiveness of the program in improving child and family outcomes.

Impact of previous gestational diabetes management on perinatal outcomes in subsequent pregnancies affected by gestational diabetes mellitus.

OBJECTIVE: To determine the impact of prior gestational diabetes mellitus (GDM) on perinatal outcomes in a subsequent GDM pregnancy. METHODS: This retrospective cohort study included 544 multiparous patients with two consecutive pregnancies between 2012-2019, where the second (index) pregnancy was affected by GDM. The primary exposure was prior GDM diagnosis, categorized into medical and dietary management. The primary outcome was a composite including need for pharmacotherapy, large-for-gestational age, or neonatal hypoglycemia. Adjusted odds ratios (aOR) were calculated using multivariable logistic regression controlling for maternal age, pre-pregnancy body mass index, and gestational age at GDM diagnosis in the index pregnancy. RESULTS: Of the 544 patients, 164 (30.1%) had prior GDM. Prior GDM significantly increased the likelihood of composite outcome compared to no prior GDM (74.4% vs. 57.4%; P < 0.001). After adjusting for confounders, prior GDM remained significantly associated with the composite outcome (aOR 2.03, 95% confidence interval [CI] 1.31-3.15). Stratifying by prior GDM treatment modality, a significant association was found for prior pharmacotherapy-controlled GDM (aOR 3.29, 95% CI 1.64-6.59), but not for prior diet-controlled GDM (aOR = 1.54, 95% CI 0.92-2.60). CONCLUSION: A history of pharmacotherapy-controlled GDM in a previous pregnancy increases odds of adverse perinatal outcomes in a subsequent GDM pregnancy.

Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled, trial.

RATIONALE AND OBJECTIVE: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate allergen-induced late asthmatic responses (LAR) in participants with allergic asthma. METHODS AND MEASUREMENTS: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed. MAIN RESULTS: Forty-six participants (mean age, 30.9 years) were randomised to benralizumab (n = 23) or placebo (n = 23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81% [95% CI, -10.69, -0.94]; P = 0.021); however, the LAR was not significantly different (least squares mean difference 2.54% [95% CI, 3.05, 8.12]; P = 0.363). Adverse events were reported for 7 (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively. CONCLUSION: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.

Canadian midwives' perspectives on the clinical impacts of point of care ultrasound in obstetrical care: A concurrent mixed-methods study.

Introduction: Point of Care Ultrasound (POCUS) is used globally in obstetrics to conduct real time bedside ultrasound scans to answer a clinical question, and it may be conducted by a non-sonography healthcare practitioner. The College of Midwives of Ontario expanded the scope of practice in 2018 to allow registered midwives to perform POCUS during clinical assessments. In response, a POCUS training curriculum for practicing midwives was developed. This paper reports on the perceptions of learners about the impact of this training on their clinical practice. Methods: We conducted a mixed-methods study to understand learner perceptions. Data collection included surveys at four time points over a year, and semi-structured interviews. Quantitative data were analyzed through descriptive statistics, and qualitative analyses used a constructivist approach to grounded theory. Results: The frequency of POCUS use within antenatal care increased among learners, with common applications including assessment of fetal presentation and confirmation of viability. POCUS was seen to holistically aid practitioners care by providing additional skills and knowledge to improve care quality and access to care, particularly for remote areas where ultrasounds are not easily available. However, participants articulated a need for clearer regulatory guidelines outlining how this technology should be applied in midwifery. Equipment purchasing and maintaining costs were a barrier for many midwives. Conclusions: Participants who had access to a device are continuing to use sonography within their clinics to provide comprehensive midwifery care informed by real-time ultrasound assessments. POCUS scans were seen to offer many benefits to improve patient care.

A Social-Ecological Model Exploring Gestational Diabetes Mellitus Screening Practices Among Antenatal Health Care Providers.

Gestational diabetes mellitus (GDM) is associated with adverse health outcomes for the pregnant individual and their baby. Screening approaches for GDM have undergone several iterations, introducing variability in practice among healthcare providers. As such, our study aimed to explore the views of antenatal providers regarding their practices of, and counseling experiences on the topic of, GDM screening in Ontario. We conducted a qualitative, grounded theory study. The study population included antenatal providers (midwives, family physicians, and obstetricians) practicing in Hamilton, Ottawa, or Sudbury, Ontario. Semi-structured telephone interviews were conducted and transcribed verbatim. Transcripts were analyzed using inductive coding upon which codes, categories, and themes were developed to generate a theory grounded in the data. Twenty-two participants were interviewed. Using the social-ecological theory, we created a model outlining four contextual levels that shaped the experiences of GDM counseling and screening: Intrapersonal factors included beliefs, knowledge, and skills; interpersonal factors characterized the patient-provider interactions; organizational strengths and challenges shaped collaboration and health services infrastructure; and finally, guidelines and policies were identified as systemic barriers to health care access and delivery. A focus on patient-centered care was a guiding principle for all care providers and permeated all four levels of the model. Patient-centered care and close attention to barriers and facilitators across intrapersonal, interpersonal, organizational, and policy domains can minimize the impact of variations in GDM screening guidelines. Among care providers, there is a desire for additional skill development related to GDM counseling, and for national consensus on optimal screening guidelines.

Impact of Antenatal Care Modifications on Gestational Diabetes Outcomes During the COVID-19 Pandemic.

BACKGROUND: Many of the adverse outcomes of gestational diabetes mellitus (GDM) are linked to excessive fetal growth, which is strongly mediated by the adequacy of maternal glycemic management. The COVID-19 pandemic led to a rapid adoption of virtual care models. We aimed to compare glycemic management, fetal growth, and perinatal outcomes before and during the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted between 2017 and 2020. Singleton pregnancies complicated by GDM were included in the study. The cohort was stratified into "before" and "during" COVID-19 subgroups, using March 11, 2020, as the demarcation time point. Women who began their GDM follow-up starting March 11, 2020, and thereafter were allocated to the COVID-19 era, whereas women who delivered before the demarcation point served as the pre-COVID-19 era. The primary outcome was the rate of large-for-gestational-age (LGA) neonates. Secondary outcomes included select maternal and neonatal adverse outcomes. RESULTS: Seven hundred seventy-five women were included in the analysis, of which 187 (24.13%) were followed during the COVID-19 era and 588 (75.87%) before the COVID-19 era. One hundred seventy-one of the 187 women (91.44%) followed during COVID-19 had at least 1 virtual follow-up visit. No virtual follow-up visits occurred before the COVID-19 era. There was no difference in the rate of LGA neonates between groups on both univariate (5.90% vs 7.30%, p=0.5) and multivariate analyses, controlling for age, ethnicity, parity, body mass index, gestational weight gain, chronic hypertension, smoking, and hypertensive disorders in pregnancy (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 0.49 to 2.51, p=0.80). In the multivariate analysis, there was no difference in composite neonatal outcome between groups (GDM diet: aOR 1.40, 95% CI 0.81 to 2.43, p=0.23; GDM medical treatment: aOR 1.20, 95% CI 0.63 to 2.43, p=0.5). CONCLUSIONS: After adjusting for differences in baseline variables, the combined virtual mode of care was not associated with a higher rate of LGA neonates or other adverse perinatal outcomes in women with GDM. Larger studies are needed to better understand the specific impact of virtual care on less common outcomes in pregnancies with GDM.

Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications.

BACKGROUND: Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. METHODS: Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). RESULTS: A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). CONCLUSIONS: Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.

Respiratory System Dynamics.

While static mechanical forces govern resting lung volumes, dynamic forces determine tidal breathing, airflow, and changes in airflow and lung volume during normal and abnormal breathing. This section will examine the mechanisms, measurement methodology, and interpretation of the dynamic changes in airflow and lung volume that occur in health and disease. We will first examine how the total work of breathing can be described by the parameters of the equation of motion, which determine the pressure required to move air into and out of the lung. This will include a detailed description of airflow characteristics and airway resistance. Next, we will review the changes in pressure and flow that determine maximal forced inspiration and expiration, which result in the maximal flow-volume loop and the clinically important forced expired volume in 1 second. We will also assess the mechanisms and interpretation of bronchodilator responsiveness, dynamic hyperinflation, and airways hyperresponsiveness.

Mediating expectations and experiences that influence birth experiences in Canada's first Alongside Midwifery Unit.

BACKGROUND: Globally, midwifery-led birthing units are associated with excellent maternal and neonatal outcomes, and positive childbirth experiences. However, little is known about what aspects of midwife-led units contribute to favorable experiences and overall satisfaction. Our aim was to explore and describe midwifery service user experiences at Canada's first Alongside Midwifery Unit (AMU). METHODS: We used a qualitative, grounded theory approach using semi-structured interviews with recipients of midwifery care at the AMU. FINDINGS: Data were collected from twenty-eight participants between September 2018 and March 2020. Our generated theory explains how birth experiences and satisfaction were influenced by how well the AMU aligned with expectations or desired experiences related to the following four themes: (1) maintaining the midwifery model of care, (2) emphasizing control and choice, (3) facilitating interprofessional relationships, and (4) appreciating the unique AMU birthing environment. CONCLUSION: Canada's first AMU met or exceeded service-user expectations, resulting in high levels of satisfaction with their birth experience. Maintaining core elements of the midwifery model of care, promoting high levels of autonomy, and facilitating positive interprofessional interactions are crucial elements contributing to childbirth satisfaction in the AMU environment.

Primary Care Framework to Monitor Preterm Infants for Neurodevelopmental Outcomes in Early Childhood.

To support decision-making in the primary care medical home, this clinical report links preterm birth and perinatal complications to early childhood developmental disability risks. It consolidates extensive contemporary outcome research from 2005 onward into an easy-to-use framework and stratifies prematurity and NICU experiences by degree of risk for developmental impairments. This framework informs and prioritizes point-of-care screening and surveillance strategies for pediatricians caring for children born preterm, guides additional assessment and referral for appropriate therapies, and offers opportunities for reassurance (when applicable) in office settings.

Prevalence, Progression, and Modifiable Risk Factors for Diabetic Retinopathy in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes. RESEARCH DESIGN AND METHODS: We conducted a multicenter, population-based prospective cohort study (2002-2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up. RESULTS: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted. CONCLUSIONS: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes.

Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma. METHODS: This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18-60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once-daily inhaled ecleralimab or placebo. Primary end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV1) during the late asthmatic response (LAR) measured by area under the curve (AUC3-7h) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide (F ENO) were secondary and exploratory end-points. RESULTS: 28 subjects were randomised to ecleralimab (n=15) or placebo (n=13). On day 84, ecleralimab significantly attenuated LAR AUC3-7h by 64% (p=0.008), LAR% by 48% (p=0.029), and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC0-2h (p=0.097) and EAR% (p=0.105). F ENO levels were significantly reduced from baseline throughout the study (p<0.05), except at 24 h post-allergen (day 43 and day 85). Overall, ecleralimab was safe and well tolerated. CONCLUSION: Ecleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation, and was safe in subjects with mild atopic asthma.

Maternal age and pregnancy outcomes in twin compared with singleton gestations.

OBJECTIVE: To estimate the association of advanced maternal age with pregnancy complications in twin pregnancies and compare it with that observed in singleton pregnancies. METHODS: A population-based retrospective cohort study of all patients with a singleton or twin hospital birth in Ontario, Canada, between 2012 and 2019. The primary outcome was preterm birth (PTB) less than 34 weeks. Pregnancy outcomes were stratified by maternal age groups in twin pregnancies and, separately, in singleton pregnancies. RESULTS: A total of 935 378 patients met the study criteria: 920503 (98.4%) had a singleton pregnancy and 14 875 (1.6%) had twins. In singletons, the rate of PTB less than 34 weeks increased progressively with increasing maternal age and was highest for patients aged 45 years or more (3.4%; adjusted risk ratio [aRR] 1.56, 95% confidence interval [CI] 1.05-2.33). By contrast, in twins, although the rate of PTB less than 34 was highest patients under 20 years of age (25.3%) and was lowest among patients aged 35-39 years (11.7%), the associations between maternal age group and the risk of PTB were not statistically significant in the adjusted analysis. CONCLUSION: Although the absolute rates of pregnancy complications are higher in twin pregnancies, there are considerable differences in the relationship between maternal age and the risk of certain complications between twin and singleton pregnancies.

Situation, Background, Assessment, Recommendation (SBAR) Education for Health Care Students: Assessment of a Training Program.

Introduction: Interprofessional communication failures are estimated to be a factor in two-thirds of serious health care-related accidents. Using a standardized communication protocol during transfer of patient information between providers improves patient safety. An interprofessional education (IPE) event for first-year health professions students was designed using the Situation, Background, Assessment, Recommendation (SBAR) tool as a structured communication framework. IPE literature, including a valid measurement tool specifically tailored for SBAR, was utilized to design the Interprofessional Team Training Day (ITTD) and evaluate learner gains in SBAR skills. Methods: Learners from six educational programs participated in ITTD, which consisted of didactics, small-group discussion, and role-play using the SBAR protocol. Individual learners were assessed using the SBAR Brief Assessment Rubric for Learner Assessment (SBAR-LA) on SBAR communication skills before and after the ITTD event. Learners received a written clinical vignette and submitted video recordings of themselves simulating the use of SBAR to communicate to another health care professional. Pre- and postrecordings were scored using the SBAR-LA rubric. Normalized gain scores were calculated to estimate the improvement attributable to ITTD. Results: SBAR-LA scores increased for 60% of participants. For skills not demonstrated before the event, the average learner acquired 44% of those skills from ITTD. Learners demonstrated statistically significant increases for five of 10 SBAR-LA skills. Discussion: The value to patient safety of utilizing structured communication between health care providers is proven; however, evaluating IPE teaching of communication skills effectiveness is challenging. Using SBAR-LA, communication skills were shown to improve following ITTD.

Exploring patients' perspectives of gestational diabetes mellitus screening and counselling in Ontario: A grounded theory study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Approaches to screening for GDM continue to evolve, introducing potential variability of care. This study explored the impact of these variations on GDM counselling and screening from the perspectives of pregnant individuals. METHODS: Following a Corbin and Strauss approach to qualitative, grounded theory we recruited 28 individuals from three cities in Ontario, Canada who had a singleton pregnancy under the care of either a midwife, family physician or obstetrician. Convenience and purposive sampling techniques were used. Semi-structured telephone interviews were conducted and transcribed verbatim between March and December 2020. Transcripts were analysed inductively resulting in codes, categories and themes. RESULTS: Three themes were derived from the data about GDM screening and counselling: 'informing oneself', 'deciding' and 'screening'. All participants, regardless of geographical region, or antenatal care provider, moved through these three steps during the GDM counselling and screening process. Differences in counselling approaches between pregnancy care providers were noted throughout the 'informing' and 'deciding' stages of care. Factors influencing these differences included communication, healthcare autonomy and patient motivation to engage with health services. No differences were noted within care provider groups across the three geographic regions. Participant experiences of GDM screening were influenced by logistical challenges and personal preferences towards testing. CONCLUSION: Informing oneself about GDM may be a crucial step for facilitating decision-making and screening uptake, with an emphasis on information provision to facilitate patient autonomy and motivation. PATIENT OR PUBLIC CONTRIBUTION: Participants of our study included patients and service users. Participants were actively involved in the study design due to the qualitative, patient-centred nature of the research methods employed. Analysis of results was structured according to the emergent themes of the data which were grounded in patient perspectives and experiences.

Allergen bronchoprovocation: correlation between FEV1 maximal percent fall and area under the FEV1 curve and impact of allergen on recovery.

BACKGROUND: House dust mite (HDM) induces greater responses than other allergens during allergen bronchoprovocation (ABP) testing. The two standardized methods for reporting results of ABP tests are the maximal percent fall in forced expiratory volume in one second (FEV1, max; %) and the area under the FEV1 vs time curve (AUC; %FEV1 x min). The relationship between these methods has not been previously investigated. AIMS: We aimed to measure the correlation between FEV1, max and AUC during the early asthmatic response (EAR) and the late asthmatic response (LAR), and to determine if the EAR recovery period for HDM would be longer than other allergens (cat, grass, horse, and ragweed). METHODS: We retrospectively calculated the AUC and correlation between FEV1, max and AUC during the EAR(0-2 h) and LAR(3-7 h) for each allergen. We compared EAR(0-3 h) and LAR(3-7 h) FEV1, max, AUC and absolute difference in FEV1, max to the most recovered FEV1 (FEV1, min). We performed pairwise comparisons of correlation and slope values using Fischer's r to z transformation and t-tests, respectively. AUC and absolute differences in FEV1, max and FEV1, min were compared using a one-way ANOVA test, followed by a post-hoc Scheffe test. RESULTS: Correlation between the FEV1, max and AUC during the EAR(0-2 h) (n = 221) was 0.807, and was 0.798 during the LAR(3-7 h) (n = 157 of 221), (difference p = 0.408). The EAR(0-3 h) AUC and FEV1, max did differ between allergens (both p < 0.0001) but the LAR(3-7 h) AUC and FEV1, max did not (p = 0.548 and 0.824, respectively). HDM did not have a larger AUC or FEV1, max, than all other allergens during the EAR(0-3 h) or the LAR(3-7 h). The absolute difference between the FEV1, max and FEV1, min during the EAR(0-3 h) did not differ between allergens (p = 0.180). CONCLUSION: The FEV1, max and AUC for both the EAR(0-2 h) and LAR(3-7 h) had excellent correlation, with no significant difference. Thus, significant bronchoconstriction will likely result in a longer recovery period. There was no evidence of delayed EAR(0-3 h) recovery following HDM challenges, so HDM did not induce a larger response compared to all the other allergens examined. REGISTRATION: Not registered. This is not a clinical trial. (This study is a retrospective analysis of data collected during several registered trials.).

Sounding the alarmins-The role of alarmin cytokines in asthma.

The alarmin cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 are epithelial cell-derived mediators that contribute to the pathobiology and pathophysiology of asthma. Released from airway epithelial cells exposed to environmental triggers, the alarmins drive airway inflammation through the release of predominantly T2 cytokines from multiple effector cells. The upstream positioning of the alarmins is an attractive pharmacological target to block multiple T2 pathways important in asthma. Blocking the function of TSLP inhibits allergen-induced responses including bronchoconstriction, airway hyperresponsiveness, and inflammation, and subsequent clinical trials of an anti-TSLP monoclonal antibody, tezepelumab, in asthma patients demonstrated improvements in lung function, airway responsiveness, inflammation, and importantly, a reduction in the rate of exacerbations. Notably, these improvements were observed in patients with T2-high and with T2-low asthma. Clinical trials blocking IL-33 and its receptor ST2 have also shown improvements in lung function and exacerbation rates; however, the impact of blocking the IL-33/ST2 axis in T2-high versus T2-low asthma is unclear. To date, there is no evidence that IL-25 blockade is beneficial in asthma. Despite the considerable overlap in the cellular functions of IL-25, IL-33, and TSLP, they appear to have distinct roles in the immunopathology of asthma.

Making Space for Midwifery in a Hospital: Exploring the Built Birth Environment of Canada's First Alongside Midwifery Unit.

BACKGROUND: Canada's first alongside midwifery unit (AMU) was intentionally informed by evidence-based birth environment design principals, building on the growing evidence that the built environment can shape experiences, satisfaction, and birth outcomes. OBJECTIVES: To assess the impact of the built environment of the AMU for both service users and midwives. This study aimed to explore the meanings that individuals attribute to the built environment and how the built environment impacted people's experiences. METHODS: We conducted a mixed-methods study using a grounded theory methodology for data collection and analysis. Our research question and data collection tools were underpinned by a sociospatial conceptual approach. All midwives and all those who received midwifery care at the unit were eligible to participate. Data were collected through a structured online survey, interviews, and focus group. RESULTS: Fifty-nine participants completed the survey, and interviews or focus group were completed with 28 service users and 14 midwives. Our findings demonstrate high levels of satisfaction with the birth environment. We developed a theoretical model, where "making space" for midwifery in the hospital contributed to positive birth experiences and overall satisfaction with the built environment. The core elements of this model include creating domestic space in an institutional setting, shifting the technological approach, and shared ownership of the unit. CONCLUSIONS: Our model for creating, shifting, and sharing as a way to make space for midwifery can serve as a template for how intentional design can be used to promote favorable outcomes and user satisfaction.

Effect of daily dosing with tiotropium against methacholine induced bronchoconstriction in asthmatics.

INTRODUCTION: Loss of bronchoprotection against direct and indirect acting stimuli following regular use of inhaled beta2-agonists occurs with both short and long-acting formulations. Comparatively little is known about the development of tolerance following regular use of inhaled muscarinic receptor antagonists. Two investigations with the short-acting muscarinic receptor antagonist ipratropium bromide have reported no tolerance after regular use against inhaled methacholine. To our knowledge, there are no data regarding loss of bronchoprotection following regular use of long-acting muscarinic receptor antagonist. We therefore looked at the effect of daily dosing with tiotropium on methacholine induced bronchoconstriction in a population of mild asthmatics. METHODS: We performed a randomized, double-blind, placebo-controlled cross-over study comparing tiotropium Respimat® 5 µg to placebo in adult asthmatics. Each treatment arm began with baseline methacholine challenge followed immediately by treatment administration. One hour later a post treatment methacholine challenge was performed. Participants dosed daily (two puffs) at home for the next six days and returned to the lab on Day 8 for a final dose of treatment 1 h prior to methacholine challenge. RESULTS: The average doubling dose increase in methacholine PD20 following a single dose of tiotropium was 3.9 doubling doses whereas that following placebo was 0.93 (p = 0.003). After regular use, methacholine PD20 was further increased to 6.4 doubling doses following tiotropium whereas that following placebo decreased by 0.57 doubling doses (p < 0.001). CONCLUSION: LAMA are indicated for use as add-on monotherapy or in triple therapy combination for poorly controlled asthma. It may be reassuring to know therefore, that regular use does not result in loss of bronchoprotection like that which occurs with beta2-agonist bronchodilators.