Deciphering the roles of subcellular distribution and interactions involving the MEF2 binding region, the ankyrin repeat binding motif and the catalytic site of HDAC4 in Drosophila neuronal morphogenesis.

BACKGROUND: Dysregulation of nucleocytoplasmic shuttling of histone deacetylase 4 (HDAC4) is associated with several neurodevelopmental and neurodegenerative disorders. Consequently, understanding the roles of nuclear and cytoplasmic HDAC4 along with the mechanisms that regulate nuclear entry and exit is an area of concerted effort. Efficient nuclear entry is dependent on binding of the transcription factor MEF2, as mutations in the MEF2 binding region result in cytoplasmic accumulation of HDAC4. It is well established that nuclear exit and cytoplasmic retention are dependent on 14-3-3-binding, and mutations that affect binding are widely used to induce nuclear accumulation of HDAC4. While regulation of HDAC4 shuttling is clearly important, there is a gap in understanding of how the nuclear and cytoplasmic distribution of HDAC4 impacts its function. Furthermore, it is unclear whether other features of the protein including the catalytic site, the MEF2-binding region and/or the ankyrin repeat binding motif influence the distribution and/or activity of HDAC4 in neurons. Since HDAC4 functions are conserved in Drosophila, and increased nuclear accumulation of HDAC4 also results in impaired neurodevelopment, we used Drosophila as a genetic model for investigation of HDAC4 function. RESULTS: Here we have generated a series of mutants for functional dissection of HDAC4 via in-depth examination of the resulting subcellular distribution and nuclear aggregation, and correlate these with developmental phenotypes resulting from their expression in well-established models of neuronal morphogenesis of the Drosophila mushroom body and eye. We found that in the mushroom body, forced sequestration of HDAC4 in the nucleus or the cytoplasm resulted in defects in axon morphogenesis. The actions of HDAC4 that resulted in impaired development were dependent on the MEF2 binding region, modulated by the ankyrin repeat binding motif, and largely independent of an intact catalytic site. In contrast, disruption to eye development was largely independent of MEF2 binding but mutation of the catalytic site significantly reduced the phenotype, indicating that HDAC4 acts in a neuronal-subtype-specific manner. CONCLUSIONS: We found that the impairments to mushroom body and eye development resulting from nuclear accumulation of HDAC4 were exacerbated by mutation of the ankyrin repeat binding motif, whereas there was a differing requirement for the MEF2 binding site and an intact catalytic site. It will be of importance to determine the binding partners of HDAC4 in nuclear aggregates and in the cytoplasm of these tissues to further understand its mechanisms of action.

Access to primary care and mortality in excess for patients with cancer in France: Results from 21 French Cancer Registries.

BACKGROUND: The impact of geographical accessibility on cancer survival has been investigated in few studies, with most research focusing on access to reference care centers, using overall mortality and limited to specific cancer sites. This study aims to examine the association of access to primary care with mortality in excess of patients with the 10 most frequent cancers in France, while controlling for socioeconomic deprivation. METHODS: This study included a total of 151,984 cases diagnosed with the 10 most common cancer sites in 21 French cancer registries between 2013 and 2015. Access to primary care was estimated using two indexes: the Accessibilité Potentielle Localisée index (access to general practitioners) and the Scale index (access to a range of primary care clinicians). Mortality in excess was modelized using an additive framework based on expected mortality based on lifetables and observed mortality. FINDINGS: Patients living in areas with less access to primary care had a greater mortality in excess for some very common cancer sites like breast (women), lung (men), liver (men and women), and colorectal cancer (men), representing 46% of patients diagnosed in our sample. The maximum effect was found for breast cancer; the excess hazard ratio was estimated to be 1.69 (95% CI, 1.20-2.38) 1 year after diagnosis and 2.26 (95% CI, 1.07-4.80) 5 years after diagnosis. INTERPRETATION: This study revealed that this differential access to primary care was associated with mortality in excess for patients with cancer and should become a priority for health policymakers to reduce these inequalities in health care accessibility.

Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study.

BACKGROUND: 13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13 programmes on invasive pneumococcal disease (IPD) and all-cause pneumonia hospitalisation in older adults (aged ≥65 years) using a retrospective observational study. METHODS: We extracted monthly IPD and all-cause pneumonia cases from laboratory and health administrative databases between January 2005 and December 2018. Using a quasi-experimental difference-in-differences design, we calculated the ratio of risk ratios (RRRs) using incidence rates of IPD or all-cause pneumonia cases before (pre-PCV13 period) and after (PCV13 period) 2010 with rates of fractures as controls. RESULTS: The rates of all IPD or PCV serotype-specific IPD for older adults in both Ontario and BC did not change in 8 years after childhood PCV13 programme implementation. All-cause pneumonia increased in Ontario (RRR 1.38, 95% CI 1.11 to 1.71) but remained unchanged in BC. CONCLUSIONS: Indirect community protection of older adults from hospitalisation with pneumococcal disease stalled despite maturation of childhood PCV13 vaccination programmes in two Canadian provinces.

The integrated behavioral model of mental health help seeking (IBM-HS): A health services utilization theory of planned behavior for accessing care.

This article introduces the integrated behavioral model of mental health help seeking (IBM-HS), a theoretical model for understanding the constructs (e.g., systemic, predisposing, and enabling factors; mental health literacy; illness perceptions; perceived need; stigma; shame; perceived benefits, motivation) that influence people's decision making around seeking professional mental health care and their ultimate access to formal treatment. The IBM-HS is a help-seeking-specific adaptation of the empirically supported integrated behavioral model and integrative model, which are themselves evolutions of the theory of planned behavior and theory of reasoned action. The IBM-HS posits that help-seeking determinants (e.g., structural forces; cultural influences; past help-seeking experience; evaluated need; mental health perceptions, knowledge, and skills; social support) influence help-seeking beliefs (i.e., outcome beliefs, experiential beliefs, beliefs about others' expectations, beliefs about others' behavior, logistical beliefs), which in turn determine their respective help-seeking mechanisms (i.e., attitude, perceived norm, personal agency). These mechanisms collectively influence help-seeking intention, which drives prospective help-seeking behavior, subject to the moderating effects of determinants. Finally, prospective behavior has reciprocal feedback loop effects on certain determinants and beliefs. This article describes the need for the IBM-HS, the model's constructs and their interrelations, measurement considerations, and how the model can be used by scholarly and applied users to systematically understand people's intention to seek professional mental health care services and what helps or hinders them from utilizing this care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Diagnostic accuracy of alternative biomarkers for acute aortic syndrome: a systematic review.

BACKGROUND: D-dimer is the only biomarker currently recommended in guidelines for the diagnosis of acute aortic syndrome (AAS). We undertook a systematic review to determine whether any alternative biomarkers could be useful in AAS diagnosis. METHODS: We searched electronic databases (including MEDLINE, EMBASE and the Cochrane Library) from inception to February 2024. Diagnostic studies were eligible if they examined biomarkers other than D-dimer for diagnosing AAS compared with a reference standard test in people presenting to the ED with symptoms of AAS. Case-control studies were identified but excluded due to high risk of bias. Selection of studies, data extraction and risk of bias assessments using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool were undertaken independently by at least two reviewers. We used narrative synthesis to summarise the findings. RESULTS: We identified 2017 citations, included 13 cohort studies (n=76-999), and excluded 38 case-control studies. Methodological quality was variable, with most included studies having unclear or high risk of bias and applicability concerns in at least one item of the QUADAS-2 tool. Only two studies reported biomarkers with sensitivity and specificity comparable to D-dimer (ie, >90% and >50%, respectively). Wang et al reported 99.1% sensitivity and 84.9% specificity for soluble ST2; however, these findings conflicted with estimates of 58% sensitivity and 70.8% specificity reported in another study. Chun and Siu reported 95.6% sensitivity and 56.1% specificity for neutrophil count, but this has not been confirmed elsewhere. CONCLUSION: There are many potential alternative biomarkers for AAS but few have been evaluated in more than one study, study designs are often weak and reported biomarker accuracy is modest or inconsistent between studies. Alternative biomarkers to D-dimer are not ready for routine clinical use. PROSPERO REGISTRATION NUMBER: CRD42022252121.

S-Nitroso-N-acetylpenicillamine impregnated latex: A new class of barrier contraception for the prevention of intercourse-associated UTIs.

Urinary tract infections (UTIs) are some of the most common infections seen in humans, affecting over half of the female population. Though easily and quickly treatable, if gone untreated for too long, UTIs can lead to narrowing of the urethra as well as bladder and kidney infections. Due to the disease potential, it is crucial to mitigate the development of UTIs throughout healthcare. Unfortunately, sexual activity and the use of condoms have been identified as common risk factors for the development of sexually acquired UTIs. Therefore, this study outlines a potential alteration to existing condom technology to decrease the risk of developing sexually acquired UTIs using S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor. Herein, varying concentrations of SNAP are integrated into commercialized condoms through a facile solvent swelling method. Physical characterization studies showed that 72%-100% of the ultimate tensile strength was maintained with lower SNAP concentrations, validating the modified condom's mechanical integrity. Additionally, the evaluation of room-temperature storage stability via NO release analysis outlined a lack of special storage conditions needed compared to commercial products. Moreover, these samples exhibited >90% relative cell viability and >96% bacterial killing, proving biocompatibility and antimicrobial properties. SNAP-Latex maintains the desired condom durability while demonstrating excellent potential as an effective new contraceptive technology to mitigate the occurrence of sexually acquired UTIs.

Investigating disparities in smoking cessation treatment for veterans with multiple sclerosis: A national analysis.

BACKGROUND AND AIMS: Smoking is a risk factor for multiple sclerosis (MS) development, symptom burden, decreased medication efficacy, and increased disease-related mortality. Veterans with MS (VwMS) smoke at critically high rates; however, treatment rates and possible disparities are unknown. To promote equitable treatment, we aim to investigate smoking cessation prescription practices for VwMS across social determinant factors. METHODS: We extracted data from the national Veterans Health Administration electronic health records between October 1, 2017, and September 30, 2018. To derive marginal estimates of the association of MS with receipt of smoking-cessation pharmacotherapy, we used propensity score matching through the extreme gradient boosting machine learning model. VwMS who smoke were matched with veterans without MS who smoke on factors including age, race, depression, and healthcare visits. To assess the marginal association of MS with different cessation treatments, we used logistic regression and conducted stratified analyses by sex, race, and ethnicity. RESULTS: The matched sample achieved a good balance across most covariates, compared to the pre-match sample. VwMS (n = 3320) had decreased odds of receiving prescriptions for nicotine patches ([Odds Ratio]OR = 0.86, p < .01), non-patch nicotine replacement therapy (NRT; OR = 0.81, p < .001), and standard practice dual NRT (OR = 0.77, p < .01), compared to matches without MS (n = 13,280). Men with MS had lower odds of receiving prescriptions for nicotine patches (OR = 0.88, p = .05), non-patch NRT (OR = 0.77, p < .001), and dual NRT (OR = 0.72, p < .001). Similarly, Black VwMS had lower odds of receiving prescriptions for patches (OR = 0.62, p < .001), non-patch NRT (OR = 0.75, p < .05), and dual NRT (OR = 0.52, p < .01). The odds of receiving prescriptions for bupropion or varenicline did not differ between VwMS and matches without MS. CONCLUSION: VwMS received significantly less smoking cessation treatment, compared to matched controls without MS, showing a critical gap in health services as VwMS are not receiving dual NRT as the standard of care. Prescription rates were especially lower for male and Black VwMS, suggesting that under-represented demographic groups outside of the white female category, most often considered as the "traditional MS" group, could be under-treated regarding smoking cessation support. This foundational work will help inform future work to promote equitable treatment and implementation of cessation interventions for people living with MS.

Recommendations to advance digital health equity: a systematic review of qualitative studies.

The World Health Organisation advocates Digital Health Technologies (DHTs) for advancing population health, yet concerns about inequitable outcomes persist. Differences in access and use of DHTs across different demographic groups can contribute to inequities. Academics and policy makers have acknowledged this issue and called for inclusive digital health strategies. This systematic review synthesizes literature on these strategies and assesses facilitators and barriers to their implementation. We searched four large databases for qualitative studies using terms relevant to digital technology, health inequities, and socio-demographic factors associated with digital exclusion summarised by the CLEARS framework (Culture, Limiting conditions, Education, Age, Residence, Socioeconomic status). Following the PRISMA guidelines, 10,401 articles were screened independently by two reviewers, with ten articles meeting our inclusion criteria. Strategies were grouped into either outreach programmes or co-design approaches. Narrative synthesis of these strategies highlighted three key themes: firstly, using user-friendly designs, which included software and website interfaces that were easy to navigate and compatible with existing devices, culturally appropriate content, and engaging features. Secondly, providing supportive infrastructure to users, which included devices, free connectivity, and non-digital options to help access healthcare. Thirdly, providing educational support from family, friends, or professionals to help individuals develop their digital literacy skills to support the use of DHTs. Recommendations for advancing digital health equity include adopting a collaborative working approach to meet users' needs, and using effective advertising to raise awareness of the available support. Further research is needed to assess the feasibility and impact of these recommendations in practice.

Story Recall in Peer Conflict Resolution Discourse Task to Identify Older Adults Testing Within Range of Cognitive Impairment.

PURPOSE: The current study used behavioral measures of discourse complexity and story recall accuracy in an expository discourse task to distinguish older adults testing within range of cognitive impairment according to a standardized cognitive screening tool in a sample of self-reported healthy older adults. METHOD: Seventy-three older adults who self-identified as healthy completed an expository discourse task and neuropsychological screener. Discourse data were used to classify participants testing within range of cognitive impairment using multiple machine learning algorithms and stability analysis for identifying reliably predictive features in an effort to maximize prediction accuracy. We hypothesized that a higher rate of pronoun use and lower scores on story recall would best classify older adults testing within range of cognitive impairment. RESULTS: The highest classification accuracy exploited a single variable in a remarkably intuitive way: using 66% story recall as a cutoff for cognitive impairment. Forcing this decision tree model to use more features or increasing its complexity did not improve accuracy. Permutation testing confirmed that the 77% accuracy and 0.18 Brier skill score achieved by the model were statistically significant (p < .00001). CONCLUSIONS: These results suggest that expository discourse tasks that place demands on executive functions, such as working memory, can be used to identify aging adults who test within range of cognitive impairment. Accurate representation of story elements in working memory is critical for coherent discourse. Our simple yet highly accurate predictive model of expository discourse provides a promising assessment for easy identification of cognitive impairment in older adults. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26543824.

Invasive Pneumococcal Disease Epidemiology and Serotype Replacement After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2022.

Background: New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada's largest province, Ontario. Methods: We included all confirmed IPD cases reported in Ontario and defined the pre-pneumococcal 13-valent conjugate vaccine (PCV13) era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and coronavirus disease 2019 (COVID-19) pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; polysaccharide 23-valent vaccine-non-PCV20; and non-vaccine-preventable [NVP]). We then compared incidence rates by age and serotype group in the pre- and post-PCV13 eras by calculating rate ratios (RRs) and their 95% CIs. Results: Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR, 0.7; 95% CI, 0.6-0.8; and RR, 0.8; 95% CI, 0.7-0.9, respectively), but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR, 1.2; 95% CI, 1.1-1.4) and ≥65 years (RR, 1.1; 95% CI, 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined, and those attributable to PCV15-non-PCV13, PCV20-non-PCV13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era. Conclusions: IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes.

The challenges of living with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) - A qualitative study.

OBJECTIVE: We sought to explore the lived experience of people with Debilitating Symptom Complexes Attributed to Ticks (DSCATT) to inform the development of a potential treatment intervention. METHODS: We conducted one-to-one in-depth, semi-structured interviews with 13 people living in Australia affected by DSCATT. Interviews were transcribed and analysed using thematic analysis. RESULTS: Although participants attributed the origin of their illness to tick bites, not all were adamant they had Lyme disease. Negative experiences in conventional healthcare were marked and were reported to exacerbate the impact of the illness and affect mental health. Further, these negative experiences propelled participants to seek unapproved treatments (by Australian standards). The desire for the illness to be acknowledged and causative agents identified was pronounced among the participant group. CONCLUSIONS: Individuals with DSCATT experience significant challenges amid a contentious healthcare landscape surrounding chronic symptoms attributed to ticks in Australia. Our findings suggest the need for empathetic, supportive and patient-centred treatments for this cohort. IMPLICATIONS FOR PUBLIC HEALTH: DSCATT results in a considerable burden across multiple domains for those affected. Negative experiences with healthcare exacerbate the suffering of people with DSCATT in Australia. New approaches that acknowledge the illness experience of people with DSCATT, alongside evidence-based treatments that encompass biopsychosocial models of care, are needed to tackle this debilitating condition.

In vivo assessment of dual-function submicron textured nitric oxide releasing catheters in a 7-day rabbit model.

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dualfunction submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. STATEMENT OF SIGNIFICANCE: Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response.

Regional brain aging: premature aging of the domain general system predicts aphasia severity.

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior.

A scoping review of active, participant centred, digital adverse events following immunization (AEFI) surveillance of WHO approved COVID-19 vaccines: A Canadian immunization Research Network study.

This scoping review examines the role of digital solutions in active, participant-centered surveillance of adverse events following initial release of COVID-19 vaccines. The goals of this paper were to examine the existing literature surrounding digital solutions and technology used for active, participant centered, AEFI surveillance of novel COVID-19 vaccines approved by WHO. This paper also aimed to identify gaps in literature surrounding digital, active, participant centered AEFI surveillance systems and to identify and describe the core components of active, participant centered, digital surveillance systems being used for post-market AEFI surveillance of WHO approved COVID-19 vaccines, with a focus on the digital solutions and technology being used, the type of AEFI detected, and the populations under surveillance. The findings highlight the need for customized surveillance systems based on local contexts and the lessons learned to improve future vaccine monitoring and pandemic preparedness.

The stroke outcome optimization project: Acute ischemic strokes from a comprehensive stroke center.

Stroke is a leading cause of disability, and Magnetic Resonance Imaging (MRI) is routinely acquired for acute stroke management. Publicly sharing these datasets can aid in the development of machine learning algorithms, particularly for lesion identification, brain health quantification, and prognosis. These algorithms thrive on large amounts of information, but require diverse datasets to avoid overfitting to specific populations or acquisitions. While there are many large public MRI datasets, few of these include acute stroke. We describe clinical MRI using diffusion-weighted, fluid-attenuated and T1-weighted modalities for 1715 individuals admitted in the upstate of South Carolina, of whom 1461 have acute ischemic stroke. Demographic and impairment data are provided for 1106 of the stroke survivors from this cohort. Our validation demonstrates that machine learning can leverage the imaging data to predict stroke severity as measured by the NIH Stroke Scale/Score (NIHSS). We share not only the raw data, but also the scripts for replicating our findings. These tools can aid in education, and provide a benchmark for validating improved methods.

A multiprovincial retrospective analysis of the incidence of myocarditis or pericarditis after mRNA vaccination compared to the incidence after SARS-CoV-2 infection.

Objective: To compare myocarditis/pericarditis risk after COVID-19 mRNA vaccination versus SARS-CoV-2 infection, and to assess if myocarditis/pericarditis risk varies by vaccine dosing interval. Methods: In this retrospective cohort study, we used linked databases in Quebec, Ontario, and British Columbia between January 26, 2020, and September 9, 2021. We included individuals aged 12 or above who received an mRNA vaccine as the second dose or were SARS-CoV-2-positive by RT-PCR. The outcome was hospitalization/emergency department visit for myocarditis/pericarditis within 21 days of exposure. We calculated age- and sex-stratified incidence ratios (IRs) of myocarditis/pericarditis following mRNA vaccination versus SARS-CoV-2 infection. We also calculated myocarditis/pericarditis incidence by vaccine type, homologous/heterologous schedule, and dosing interval. We pooled province-specific estimates using meta-analysis. Results: Following 18,860,817 mRNA vaccinations and 860,335 SARS-CoV-2 infections, we observed 686 and 160 myocarditis/pericarditis cases, respectively. Myocarditis/pericarditis incidence was lower after vaccination than infection (IR [BNT162b2/SARS-CoV-2], 0.14; 95%CI, 0.07-0.29; IR [mRNA-1273/SARS-CoV-2], 0.28; 95%CI, 0.20-0.39). Within the vaccinated cohort, myocarditis/pericarditis incidence was lower with longer dosing intervals; IR (56 or more days/15-30 days) was 0.28 (95%CI, 0.19-0.41) for BNT162b2 and 0.26 (95%CI, 0.18-0.38) for mRNA-1273. Conclusion: Myocarditis/pericarditis risk was lower after mRNA vaccination than SARS-CoV-2 infection, and with longer intervals between primary vaccine doses.