Climate-conscious inhaler prescribing for family physicians.

OBJECTIVE: To provide family physicians with prescribing and diagnostic strategies that can reduce carbon emissions associated with inhalers. SOURCES OF INFORMATION: This review is based on the authors' experience developing the climate-conscious inhaler prescribing playbooks and courses for CASCADES (Creating a Sustainable Canadian Health System in a Climate Crisis). The approach was refined through patient and provider feedback since the first playbook was published in 2021. PubMed was also searched for relevant publications on inhaler use, asthma management, and chronic obstructive pulmonary disease (COPD) management. Current asthma and COPD guidelines were also reviewed. MAIN MESSAGE: There is growing acknowledgment of the substantial impact that inhalers have on climate emissions generated by the health sector. Recent surveys indicate that most Canadian patients care about climate change and would be willing to opt for less carbon-intensive treatment and care delivery options where available. Beyond inhaler choice, there are many opportunities to address the climate impacts of respiratory care and enhance quality of care. Working with patients to ensure they are using the right medications in the right ways will produce both carbon savings and better health outcomes. The climate crisis can therefore serve as a catalyst for improving treatment of patients with respiratory conditions. Family physicians may reduce carbon emissions associated with inhalers by reducing unnecessary inhaler prescribing; ensuring patients' control of asthma and COPD is optimized; considering whether a more sustainable inhaler may be appropriate; optimizing dosing technique to reduce emissions and waste; and disposing of inhalers appropriately if possible. CONCLUSION: Family physicians may reduce carbon emissions associated with inhalers through the following strategies: confirming diagnosis, controlling disease, considering inhaler type, optimizing dosing technique, and encouraging appropriate disposal.

Context-Specific Stress Causes Compartmentalized SARM1 Activation and Local Degeneration in Cortical Neurons.

Sterile alpha and TIR motif containing 1 (SARM1) is an inducible NADase that localizes to mitochondria throughout neurons and senses metabolic changes that occur after injury. Minimal proteomic changes are observed upon either SARM1 depletion or activation, suggesting that SARM1 does not exert broad effects on neuronal protein homeostasis. However, whether SARM1 activation occurs throughout the neuron in response to injury and cell stress remains largely unknown. Using a semiautomated imaging pipeline and a custom-built deep learning scoring algorithm, we studied degeneration in both mixed-sex mouse primary cortical neurons and male human-induced pluripotent stem cell-derived cortical neurons in response to a number of different stressors. We show that SARM1 activation is differentially restricted to specific neuronal compartments depending on the stressor. Cortical neurons undergo SARM1-dependent axon degeneration after mechanical transection, and SARM1 activation is limited to the axonal compartment distal to the injury site. However, global SARM1 activation following vacor treatment causes both cell body and axon degeneration. Context-specific stressors, such as microtubule dysfunction and mitochondrial stress, induce axonal SARM1 activation leading to SARM1-dependent axon degeneration and SARM1-independent cell body death. Our data reveal that compartment-specific SARM1-mediated death signaling is dependent on the type of injury and cellular stressor.

Food Allergy Reaction Severity and Management in a Diverse Population.

BACKGROUND: Definitive treatment for food allergy reactions including anaphylaxis varies widely by reaction severity and socioeconomic status, but little data exist to characterize the relationship between severity, management, and race and ethnicity. OBJECTIVE: To analyze the differences in reaction severity, epinephrine use, and emergency room (ER) use by race and ethnicity in a large, diverse, food-allergic cohort. METHODS: We analyzed intake data from participants in the Food Allergy Outcomes Related to White and African-American Racial Differences cohort on the history of food allergy reactions, severity of the reactions, and management associated with each reaction. We used descriptive statistics as well as mixed-effects logistic and Poisson models to describe the differences in reaction severity, ER visits, and total lifetime epinephrine use by race and ethnicity. RESULTS: A total of 784 children were included in the analysis: 425 (54.2%) were non-Hispanic White, 282 (36.0%) were non-Hispanic Black, and 77 (9.8%) were Hispanic/Latino. Non-Hispanic Black children had increased odds of more severe reactions (odds ratio, 1.7; 95% CI, 1.2-2.3) and higher odds of going to the ER (odds ratio, 2.8; 95% CI, 1.4-5.4). Both non-Hispanic Black (incidence rate ratio, 0.4; 95% CI, 0.3-0.5) and Hispanic/Latino (incidence rate ratio, 0.3; 95% CI, 0.2-0.5) children had lower rates of total lifetime epinephrine use. CONCLUSIONS: There are significant disparities in the severity and treatment of food allergy reactions by race and ethnicity, resulting in increased ER use and decreased total lifetime epinephrine use. Equipping parents with resources and tools on management of food allergy reactions may result in decreased disparity in access to definitive care.

Reductions in inhaler greenhouse gas emissions by addressing care gaps in asthma and chronic obstructive pulmonary disease: an analysis.

INTRODUCTION: Climate change from greenhouse gas (GHG) emissions represents one of the greatest public health threats of our time. Inhalers (and particularly metred-dose inhalers (MDIs)) used for asthma and chronic obstructive pulmonary disease (COPD), constitute an important source of GHGs. In this analysis, we aimed to estimate the carbon footprint impact of improving three distinct aspects of respiratory care that drive avoidable inhaler use in Canada. METHODS: We used published data to estimate the prevalence of misdiagnosed disease, existing inhaler use patterns, medication class distributions, inhaler type distributions and GHGs associated with inhaler actuations, to quantify annual GHG emissions in Canada: (1) attributable to asthma and COPD misdiagnosis; (2) attributable to overuse of rescue inhalers due to suboptimally controlled symptoms; and (3) avoidable by switching 25% of patients with existing asthma and COPD to an otherwise comparable therapeutic option with a lower GHG footprint. RESULTS: We identified the following avoidable annual GHG emissions: (1) ~49 100 GHG metric tons (MTs) due to misdiagnosed disease; (2) ~143 000 GHG MTs due to suboptimal symptom control; and (3) ~262 100 GHG MTs due to preferential prescription of strategies featuring MDIs over lower-GHG-emitting options (when 25% of patients are switched to lower GHG alternatives). Combined, the GHG emission reductions from bridging these gaps would be the equivalent to taking ~101 100 vehicles off the roads each year. CONCLUSIONS: Our analysis shows that the carbon savings from addressing misdiagnosis and suboptimal disease control are comparable to those achievable by switching one in four patients to lower GHG-emitting therapeutic strategies. Behaviour change strategies required to achieve and sustain delivery of evidence-based real-world care are complex, but the added identified incentive of carbon footprint reduction may in itself prove to be a powerful motivator for change among providers and patients. This additional benefit can be leveraged in future behaviour change interventions.

Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (-)-Eugenial C.

Metal-hydride hydrogen atom transfer (MHAT) has emerged as a useful tool to form quaternary carbons from alkenes via hydrofunctionalization. Methods to date that cross-couple alkenes with sp3 partners rely on heterobimetallic catalysis to merge the two cycles. Here, we report an iron-only cross-coupling via putative MHAT/SH2 steps that solves a key stereochemical problem in the synthesis of meroterpenoid eugenial C and obviates the need for nickel. The concise synthesis benefits from a conformationally locked o,o'-disubstituted benzyl bromide and a locally sourced chiral pool terpene coupling partner.

Validation of Linear Range HER2/Estrogen Receptor/Progesterone Receptor IHControls for Daily Quality Assurance.

OBJECTIVES: To evaluate a new US Food and Drug Administration (FDA)-cleared immunohistochemistry (IHC) control (IHControls [Boston Cell Standards]) comprising peptide epitopes for HER2, estrogen receptor (ER), and progesterone receptor (PR) attached to cell-sized microspheres and to compare its performance against conventional tissue controls. METHODS: IHControls and tissue/cell line controls for HER2, ER, and PR were compared side by side daily at 5 clinical IHC laboratories for 1 to 2 months. Separately, the sensitivity of the 2 types of controls was evaluated in simulated IHC assay failure experiments by diluting the primary antibody. Additional evaluations included lot-to-lot manufacturing reproducibility of 3 independent lots and specificity against 26 antigenically irrelevant IHC stains. RESULTS: Side-by-side testing revealed a 99.6% concordance between IHControls and tissue controls across 5 IHC laboratories and 766 individual evaluations. Three discordant quality control events were the result of operator error. Simulated assay failure data showed that both IHControls and tissue controls are similarly capable of detecting IHC staining errors. Manufacturing reproducibility of IHControls showed less than 10% variability (coefficient of variation). No cross-reactions were detected from 26 antigenically irrelevant IHC stains. CONCLUSIONS: IHControls, the first FDA-cleared IHC controls, can sensitively and accurately detect IHC assay problems, similar to tissue controls.

Teaching poverty and health: importing transformative learning into the structures and paradigms of medical education.

Background: As a paradigm of education that emphasizes equity and social justice, transformative education aims to improve societal structures by inspiring learners to become agents of social change. In an attempt to contribute to transformative education, the University of Toronto MD program implemented a workshop on poverty and health that included tutors with lived experience of poverty. This research aimed to examine how tutors, as members of a group that faces structural oppression, understood their participation in the workshop. Methods: This research drew on qualitative case study methodology and interview data, using the concept of transformative education to direct data analysis and interpretation. Results: Our findings centred around two broad themes: misalignments between transformative learning and the structures of medical education; and unintended consequences of transformative education within the dominant paradigms of medical education. These misalignments and unintended consequences provided insight into how courses operating within the structures, hierarchies and paradigms of medical education may be limited in their potential to contribute to transformative education. Conclusions: To be truly transformative, medical education must be willing to try to modify structures that reinforce oppression rather than integrating marginalized persons into educational processes that maintain social inequity.

Contexte: En tant que paradigme favorisant l'équité et la justice sociale, l'éducation axée sur la transformation vise à améliorer les structures sociétales en inspirant les apprenants à devenir des agents du changement social. Dans une visée d'éducation transformatrice, le programme de doctorat en médecine de l'Université de Toronto a mis en place un atelier sur le thème de la santé et la pauvreté auquel participaient des tuteurs ayant une expérience vécue de la pauvreté. Notre recherche visait à examiner comment les tuteurs, en tant que membres d'un groupe confronté à l'oppression structurelle, ont compris leur participation à l'atelier. Méthodes: Cette recherche qualitative s'est appuyée sur une méthodologie d'étude de cas et sur des données d'entrevue, en utilisant le concept d'éducation transformatrice comme prisme pour l'analyse et l'interprétation des données. Résultats: Nos résultats s'articulent autour de deux grands thèmes : les décalages entre l'apprentissage transformateur et les structures de l'éducation médicale, et les conséquences inattendues de l'éducation transformatrice au sein des paradigmes dominants de l'éducation médicale. Ces divergences et ces conséquences non voulues ont permis de constater que les cours qui sont ancrés dans les structures, les hiérarchies et les paradigmes contribueront peu à l'éducation transformatrice. Conclusions: Pour que l'éducation médicale soit véritablement transformatrice, il faut qu'il y ait une volonté de modifier les structures qui renforcent l'oppression plutôt que de faire entrer les personnes marginalisées dans des processus éducatifs qui perpétuent l'inégalité sociale.

Herbivory on the pedunculate oak along an urbanization gradient in Europe: Effects of impervious surface, local tree cover, and insect feeding guild.

Urbanization is an important driver of the diversity and abundance of tree-associated insect herbivores, but its consequences for insect herbivory are poorly understood. A likely source of variability among studies is the insufficient consideration of intra-urban variability in forest cover. With the help of citizen scientists, we investigated the independent and interactive effects of local canopy cover and percentage of impervious surface on insect herbivory in the pedunculate oak (Quercus robur L.) throughout most of its geographic range in Europe. We found that the damage caused by chewing insect herbivores as well as the incidence of leaf-mining and gall-inducing herbivores consistently decreased with increasing impervious surface around focal oaks. Herbivory by chewing herbivores increased with increasing forest cover, regardless of impervious surface. In contrast, an increase in local canopy cover buffered the negative effect of impervious surface on leaf miners and strengthened its effect on gall inducers. These results show that-just like in non-urban areas-plant-herbivore interactions in cities are structured by a complex set of interacting factors. This highlights that local habitat characteristics within cities have the potential to attenuate or modify the effect of impervious surfaces on biotic interactions.

Ocular abnormalities at diagnosis and after the completion of treatment in children and adolescents with newly diagnosed acute lymphoblastic leukemia.

BACKGROUND: Ocular abnormalities (OA) in pediatric patients with acute lymphoblastic leukemia (ALL) are common findings both at diagnosis and later in follow-up. The frequency, predictors, and prognostic impact of OA in the context of recent ALL protocols are not well characterized. PROCEDURE: Single-center retrospective analysis of the medical records of 224 patients with ALL enrolled on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-001. RESULTS: Overall, 217 (98%) patients had at least one ophthalmic exam. Retinal hemorrhages were the most frequent abnormalities at diagnosis (11%) and cataracts at later time points (13%). OA at diagnosis were associated with age ≥10 years and with the severity of anemia and thrombocytopenia; they were also univariately associated with lower 5-year event-free survival (EFS) (high risk [HR] = 3.09 [95% CI: 1.38-6.94]; p = .006), but not in a disease-free survival (DFS) model adjusted for end-induction minimal residual disease (p = .82). The cumulative incidence of cataract was 13.1% ± 2.8% at 43 months from diagnosis; its development was associated with high presenting white blood cell count (≥50,000/µl) (p = .010), male sex (p = .036), higher risk group (p = .025), and cranial radiation (p = .004). Cataract was associated with decreased visual acuity. CONCLUSIONS: OA at diagnosis, present in 12% of patients, were associated with older age, anemia, and thrombocytopenia and did not carry a significant prognostic impact. Cataracts were detected in over 10% of patients and were associated with decreased visual acuity, thus supporting routine screening after completion of therapy, especially for those treated with high-risk protocols.

Technical note: 3D-printed phantom for dedicated cardiac protocols and geometries in nuclear medicine.

PURPOSE: The purpose of this study was to create and validate a 3D-printed nuclear cardiac phantom for low cost, user-friendly design and easy implementation with modern cardiac SPECT systems. This new phantom design aims to address common problems with commercial phantoms such as lengthy setup, prohibitive cost, and overly large size, while improving the overall functionality of the phantom. METHODS: The phantom was developed using computer aided design software and fabricated with a 3D printer using optimized watertight printing protocols. The phantom design includes six low perfusion lesions within a stylized myocardium of the left ventricle that are placed in the common quantitation sectors for polar maps. The validation of this phantom was completed with two dedicated cardiac SPECT systems; a dual head gamma camera and a multi-pinhole CZT system. Multiple SPECT acquisitions were used to demonstrate the functionality of the phantom. Polar maps were reconstructed and used to score the contrast detectability based on the number of visible low contrast objects representing "lesions." RESULTS: The images reconstructed from the various acquisitions on both SPECT systems closely resemble a clinical examination. Lesion visibility followed the expected relationships between protocol changes affecting contrast and spatial resolution. Lesion visibility improved with iterative reconstruction against filtered back projection. CONCLUSION: A phantom of a stylized left ventricle with fillable myocardium was developed, 3D printed, and implemented for cardiac nuclear medicine. The phantom simulates the task of perfusion imaging and successfully demonstrates differences in image quality depending on imaging protocol. This study validates the 3D-printed design as a low cost and user-friendly phantom that can be easily scanned and scored using various systems, in particular those implementing a nontraditional cardio-centric geometry.