The evolution of health system planning and implementation of maternal telehealth services during the COVID-19 Pandemic.

Background: Differential access to healthcare is associated with disparities in maternal outcomes. Telehealth is one approach for improving access to maternal services. However, little is known regarding how health systems leverage telehealth to close the access gap. Objective: This study examines how health systems have approached decisions about using telehealth for maternal services before and during the COVID-19 public health emergency and what factors were considered. Methods: We conducted semi-structured interviews with 15 health system leaders between July and October 2021 and June and August 2022. We used a rapid analysis followed by a content analysis approach. Results: Five health systems did not provide maternal telehealth services before the PHE due to a lack of reimbursement. Two health systems provided limited services as research endeavors, and one had integrated telehealth into routine maternity care. During the PHE, all transitioned to telehealth, with the primary consideration being patient and staff safety. At the time of the interview, key considerations shifted to patient access, patient preferences, patient complexity, return on investment, and staff burnout. However, several barriers impacted telehealth use, including coverage of portable devices and connectivity. These issues were reported to be common among underinsured, low-income, and rural patients. Health systems with particularly advanced capabilities worked on approaches to fill access gaps for these patients. Conclusion: Some health systems prioritized telehealth to improve access to high-quality maternal services for patients at the highest risk of adverse outcomes. However, policy and patient-level barriers to equitable implementation of these services persist.

Defining the cardiovascular phenotype of adults with Alström syndrome.

BACKGROUND: >40% of infants with Alström Syndrome (AS) present with a transient, severe cardiomyopathy in the first months of life, with apparent recovery in survivors. One in five individuals then develop a later-onset cardiomyopathy but wide clinical variability is observed, even within the same family. The rationale for this study is to provide a comprehensive evaluation of the cardiovascular phenotype in adults with AS. METHODS: Adults attending the National Centre for AS in England were studied. All patients underwent biochemical, 12- lead electrocardiography, echocardiography, and cardiovascular magnetic resonance imaging. RESULTS: 47 adults with AS (64% male; mean age 33 years; 66% white British) were studied. Seven (15%) survived infantile cardiomyopathy and 23 (49%) developed adult-onset cardiomyopathy. Conventional risk factors for cardiovascular disease were present in 39 (83%). Abnormalities were present on biomarkers in 16 (34%), ECG 30 (64%), echocardiography 19 (40%) and CMR 31 (66%). Coronary artery imaging was performed in six (13%), with abnormalities in two. Cardiac, renal, and liver markers were more often impaired in older patients, with impaired left ventricular ejection fraction, reduced global longitudinal strain and late enhancement. 6 (13%) had severe pulmonary hypertension (mean pulmonary artery pressure 46 mmHg) due to left heart disease on invasive testing. CONCLUSION: Cardiomyopathy is common in adults with AS, complicated in a significant proportion by atherosclerotic coronary artery disease and restrictive cardiomyopathy, confirmed on CMR and invasive testing. With advancing age, cardiovascular complications are compounded by contemporaneous renal and liver disease.

Combined Melanocytic Nevus and Nevus Sebaceus: A Case Series and Review of the Literature.

ABSTRACT: Nevus sebaceus is a rare congenital hamartoma with clinical and histopathological features that change with puberty. It has been associated with a number of secondary neoplasms, most of which are thought to derive from follicular germ cells. In this article, the authors describe a total of 3 cases of combined melanocytic nevus and nevus sebaceus to highlight this rare finding.

Disparities in Maternal Health Visits Between Rural and Urban Communities in the United States, 2016-2018.

OBJECTIVE: The objective was to estimate the rural-urban differences in the receipt of prepregnancy, prenatal, and postpartum services. METHODS: The authors conducted a cross-sectional data analysis using data from the Pregnancy Risk Assessment and Monitoring System from 2016 to 2018 to analyze rural-urban differences in the receipt of medical visits and care content delivery during the prepregnancy year, as well as the prenatal and postpartum periods among birthing people in the US, using survey-weighted multivariable logistic regression models. RESULTS: Rural-dwelling birthing people were significantly less likely to attend a medical visit in the prepregnancy year or postpartum period, even when controlled for sociodemographic and clinical characteristics. Compared to their urban counterparts, they were also less likely to receive comprehensive screening and counseling in the prepregnancy and postpartum maternity phases. CONCLUSION: Efforts to ameliorate rural-urban differences in maternal care access and quality should explicitly adopt multilevel, systemic approaches to policy and program implementation and evaluation. Policymakers and practitioners should consider telehealth as a potential complementary tool to minimize gaps in quality of care which disproportionately impact rural-dwelling birthing people.

Arrhythmogenesis in Fabry Disease.

PURPOSE OF REVIEW: Fabry Disease (FD) is a rare lysosomal storage disorder characterised by multiorgan accumulation of glycosphingolipid due to deficiency in the enzyme α-galactosidase A. Cardiac sphingolipid accumulation triggers various types of arrhythmias, predominantly ventricular arrhythmia, bradyarrhythmia, and atrial fibrillation. Arrhythmia is likely the primary contributor to FD mortality with sudden cardiac death, the most frequent cardiac mode of death. Traditionally FD was seen as a storage cardiomyopathy triggering left ventricular hypertrophy, diastolic dysfunction, and ultimately, systolic dysfunction in advanced disease. The purpose of this review is to outline the current evidence exploring novel mechanisms underlying the arrhythmia substrate. RECENT FINDINGS: There is growing evidence that FD cardiomyopathy is a primary arrhythmic disease with each stage of cardiomyopathy (accumulation, hypertrophy, inflammation, and fibrosis) contributing to the arrhythmia substrate via various intracellular, extracellular, and environmental mechanisms. It is therefore important to understand how these mechanisms contribute to an individual's risk of arrhythmia in FD. In this review, we outline the epidemiology of arrhythmia, pathophysiology of arrhythmogenesis, risk stratification, and cardiac therapy in FD. We explore how advances in conventional cardiac investigations performed in FD patients including 12-lead electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging have enabled early detection of pro-arrhythmic substrate. This has allowed for appropriate risk stratification of FD patients. This paves the way for future work exploring the development of therapeutic initiatives and risk prediction models to reduce the burden of arrhythmia.

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant ( P <0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics.

BRAF Mutated and Morphologically Spitzoid Tumors, a Subgroup of Melanocytic Neoplasms Difficult to Distinguish From True Spitz Neoplasms.

Drivers of Spitz neoplasms include activating point mutations in HRAS and Spitz-associated genomic fusions. It has become evident that some BRAF -mutated melanocytic neoplasms can morphologically mimic Spitz tumors (STs). These have been termed BRAF mutated and morphologically spitzoid (BAMS). In this study, 17 experts from the International Melanoma Pathology Study Group assessed 54 cases which included 40 BAMS and 14 true STs. The participants reviewed the cases blinded to the genomic data and selected among several diagnostic options, including BAMS, ST, melanoma, and other. A total of 38% of all diagnostic selections in the BAMS cases were for BAMS, whereas 32% were for ST. In 22 of the BAMS cases, the favored diagnosis was BAMS, whereas in 17 of the BAMS cases, the favored diagnosis was ST. Among the 20 cases in the total group of 54 with the highest number of votes for ST, half were BAMS. Of BAMS, 75% had a number of votes for ST that was within the SD of votes for ST seen among true ST cases. There was poor interobserver agreement for the precise diagnosis of the BAMS (kappa = 0.16) but good agreement that these cases were not melanoma (kappa = 0.7). BAMS nevi/tumors can closely mimic Spitz neoplasms. Expert melanoma pathologists in this study favored a diagnosis of ST in nearly half of the BAMS cases. There are BAMS cases that even experts cannot morphologically distinguish from true Spitz neoplasms.

Who are vaccine champions and what implementation strategies do they use to improve adolescent HPV vaccination? Findings from a national survey of primary care professionals.

BACKGROUND: Implementation science researchers often cite clinical champions as critical to overcoming organizational resistance and other barriers to the implementation of evidence-based health services, yet relatively little is known about who champions are or how they effect change. To inform future efforts to identify and engage champions to support HPV vaccination, we sought to describe the key characteristics and strategies of vaccine champions working in adolescent primary care. METHODS: In 2022, we conducted a national survey with a web-based panel of 2527 primary care professionals (PCPs) with a role in adolescent HPV vaccination (57% response rate). Our sample consisted of pediatricians (26%), family medicine physicians (22%), advanced practice providers (24%), and nursing staff (28%). Our survey assessed PCPs' experience with vaccine champions, defined as health care professionals "known for helping their colleagues improve vaccination rates." RESULTS: Overall, 85% of PCPs reported currently working with one or more vaccine champions. Among these 2144 PCPs, most identified the champion with whom they worked most closely as being a physician (40%) or nurse (40%). Almost all identified champions worked to improve vaccination rates for vaccines in general (45%) or HPV vaccine specifically (49%). PCPs commonly reported that champion implementation strategies included sharing information (79%), encouragement (62%), and vaccination data (59%) with colleagues, but less than half reported that champions led quality improvement projects (39%). Most PCPs perceived their closest champion as being moderately to extremely effective at improving vaccination rates (91%). PCPs who did versus did not work with champions more often recommended HPV vaccination at the earliest opportunity of ages 9-10 rather than later ages (44% vs. 33%, p < 0.001). CONCLUSIONS: Findings of our national study suggest that vaccine champions are common in adolescent primary care, but only a minority lead quality improvement projects. Interventionists seeking to identify champions to improve HPV vaccination rates can expect to find them among both physicians and nurses, but should be prepared to offer support to more fully engage them in implementing interventions.

North Carolina Medicaid System Perspectives on Substance Use Disorder Treatment Policy Changes During the COVID-19 Pandemic.

OBJECTIVE: This study aimed to describe perspectives from stakeholders involved in the Medicaid system in North Carolina regarding substance use disorder (SUD) treatment policy changes during the coronavirus disease 2019 pandemic. METHODS: We conducted semistructured interviews in early 2022 with state agency representatives, Medicaid managed care organizations, and Medicaid providers (n = 22) as well as 3 focus groups of Medicaid beneficiaries with SUD (n = 14). Interviews and focus groups focused on 4 topics: policies, meeting needs during COVID, demand for SUD services, and staffing. RESULTS: Overall, policy changes, such as telehealth and take-home methadone, were considered beneficial, with participants displaying substantial support for both policies. Shifting demand for services, staffing shortages, and technology barriers presented significant challenges. Innovative benefits and services were used to adapt to these challenges, including the provision of digital devices and data plans to improve access to telehealth. CONCLUSIONS: Perspectives from Medicaid stakeholders, including state organizations to beneficiaries, support the continuation of SUD policy changes that occurred. Staffing shortages remain a substantial barrier. Based on the participants' positive responses to the SUD policy changes made during the coronavirus disease 2019 pandemic, such as take-home methadone and telehealth initiation of buprenorphine, these changes should be continued. Additional steps are needed to ensure payment parity for telehealth services.

Virtual quality improvement collaborative with primary care practices during COVID-19: a case study within a clinically integrated network.

INTRODUCTION: Quality improvement collaboratives (QICs) are a common approach to facilitate practice change and improve care delivery. Attention to QIC implementation processes and outcomes can inform best practices for designing and delivering collaborative content. In partnership with a clinically integrated network, we evaluated implementation outcomes for a virtual QIC with independent primary care practices delivered during COVID-19. METHODS: We conducted a longitudinal case study evaluation of a virtual QIC in which practices participated in bimonthly online meetings and monthly tailored QI coaching sessions from July 2020 to June 2021. Implementation outcomes included: (1) level of engagement (meeting attendance and poll questions), (2) QI capacity (assessments completed by QI coaches), (3) use of QI tools (plan-do-check-act (PDCA) cycles started and completed) and (4) participant perceptions of acceptability (interviews and surveys). RESULTS: Seven clinics from five primary care practices participated in the virtual QIC. Of the seven sites, five were community health centres, three were in rural counties and clinic size ranged from 1 to 7 physicians. For engagement, all practices had at least one member attend all online QIC meetings and most (9/11 (82%)) poll respondents reported meeting with their QI coach at least once per month. For QI capacity, practice-level scores showed improvements in foundational, intermediate and advanced QI work. For QI tools used, 26 PDCA cycles were initiated with 9 completed. Most (10/11 (91%)) survey respondents were satisfied with their virtual QIC experience. Twelve interviews revealed additional themes such as challenges in obtaining real-time data and working with multiple electronic medical record systems. DISCUSSION: A virtual QIC conducted with independent primary care practices during COVID-19 resulted in high participation and satisfaction. QI capacity and use of QI tools increased over 1 year. These implementation outcomes suggest that virtual QICs may be an attractive alternative to engage independent practices in QI work.

Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.

Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.

State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for 'all-optical' electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.

Using intervention mapping to develop an implementation strategy to improve timely uptake of streamlined birth-dose vaccines in the Democratic Republic of the Congo.

Despite the policy recommendation and effectiveness of administering the hepatitis B birth-dose vaccine (HepB-BD) to newborns to prevent mother-to-child hepatitis B transmission, timely uptake remains an issue. Countries adopting the HepB-BD to their national immunization schedule report programmatic challenges to administering the vaccine within the recommended 24-hour window after delivery. Further, while the World Health Organization recommends streamlining three birth-dose vaccines (HepB-BD, BCG, and OPV0), scarce Sub-Saharan(SSA)-based literature reports on a streamlined and timely approach to birth-dose vaccines. As more SSA countries adopt the new birth-dose vaccine to their immunization schedules, a systematically developed implementation strategy-Vaccination of Newborns-Innovative Strategies to Hasten Birth-Dose vaccines' delivery (VANISH-BD)-will facilitate the adoption and implementation of timely birth-dose vaccine uptake. In this paper, we describe the development of the implementation strategy using intervention mapping, an evidence-based and theory-driven approach. We report on the development of our intervention, beginning with the needs assessment based in Kinshasa Province, Democratic Republic of the Congo (DRC), informing step 1 of intervention mapping. The intervention is contextually relevant, locally produced, sustainable, and designed to improve timely birth-dose vaccine uptake in the DRC. We intend to inform future implementers about improving timely and streamlined birth-dose vaccine uptake and for VANISH-BD to be adapted for similar contexts.

Telehealth Use by Pregnancy Stage Among Commercially Insured Patients in the United States, 2016-2019.

Introduction: Relatively little is known about the proportion of maternal health services utilized through telehealth and whether rural-urban disparities in telehealth use exist throughout antenatal, delivery, and postpartum phases of maternal services. In this study, we describe patterns of care, including telehealth utilization, by rurality and racial/ethnic composition of the health service area during the antenatal, labor/delivery, and postpartum stages of pregnancy among commercially insured patients between 2016 and 2019. Methods: We present univariate and comparative descriptive statistics of patient and facility characteristics and site of care by the degree of rurality and racial/ethnic composition of the health service area (defined as geozips). The individual-level utilization data for 238,695 patients were aggregated to the geo-zip level (n = 404). Results: Between 2016 and 2019, 3.5% of pregnancy, delivery, and postpartum-related visits among commercially insured patients were delivered through telehealth. Telehealth use was higher in the antenatal (3.5% of claim lines) and postpartum (4.1% of claim lines) periods, compared with labor and delivery (0.7% of claim lines). We also found that the proportion of telehealth services (of total services billed) increased with the share of Black and Latinx residents at the geozip level. Discussion: Our findings highlight disparities in telehealth use, consistent with findings from studies using different data sources and time periods. Future research is needed to examine whether the relative differences in proportion of telehealth services, even if small, are associated with telehealth capacity in the hospital or community and why the proportion of telehealth services differs across community-level characteristics, specifically rurality and proportion of Black and Latinx residents.

Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases the risk of stroke, heart failure, dementia, and hospitalization. Obesity significantly increases AF risk, both directly and indirectly, through related conditions, like hypertension, diabetes, and heart failure. Obesity-driven structural and electrical remodeling contribute to AF via several reported mechanisms, including adiposity, inflammation, fibrosis, oxidative stress, ion channel alterations, and autonomic dysfunction. In particular, expanding epicardial adipose tissue during obesity has been suggested as a key driver of AF via paracrine signaling and direct infiltration. Weight loss has been shown to reverse these changes and reduce AF risk and recurrence after ablation. However, studies on how obesity affects pharmacologic or interventional AF treatments are limited. In this review, we discuss mechanisms by which obesity mediates AF and treatment outcomes, aiming to provide insight into obesity-drug interactions and guide personalized treatment for this patient subgroup.

Childhood immunization uptake determinants in Kinshasa, Democratic Republic of the Congo: ordered regressions to assess timely infant vaccines administered at birth and 6-weeks.

BACKGROUND: Despite global efforts to reduce preventable childhood illness by distributing infant vaccines, immunization coverage in sub-Saharan African settings remains low. Further, timely administration of vaccines at birth-tuberculosis (Bacille Calmette-Guérin [BCG]) and polio (OPV0)-remains inconsistent. As countries such as Democratic Republic of the Congo (DRC) prepare to add yet another birth-dose vaccine to their immunization schedule, this study aims to improve current and future birth-dose immunization coverage by understanding the determinants of infants receiving vaccinations within the national timeframe. METHODS: The study used two ordered regression models to assess barriers to timely BCG and first round of the hepatitis B (HepB3) immunization series across multiple time points using the Andersen Behavioral Model to conceptualize determinants at various levels. The assessment leveraged survey data collected during a continuous quality improvement study (NCT03048669) conducted in 105 maternity centers throughout Kinshasa Province, DRC. The final sample included 2398 (BCG analysis) and 2268 (HepB3 analysis) women-infant dyads living with HIV. RESULTS: Between 2016 and 2020, 1981 infants (82.6%) received the BCG vaccine, and 1551 (68.4%) received the first dose of HepB3 vaccine. Of those who received the BCG vaccine, 26.3%, 43.5%, and 12.8% received BCG within 24 h, between one and seven days, and between one and 14 weeks, respectively. Of infants who received the HepB3 vaccine, 22.4% received it within six weeks, and 46% between six and 14 weeks of life. Many factors were positively associated with BCG uptake, including higher maternal education, household wealth, higher facility general readiness score, and religious-affiliated facility ownership. The factors influencing HepB3 uptake included older maternal age, higher education level, household wealth, transport by taxi to a facility, higher facility general and immunization readiness scores, and religious-affiliated facility ownership. CONCLUSIONS: This study demonstrated that the study participants' uptake of vaccines was consistent with the country average, but not in a timely manner. Various factors were associated with timely uptake of BCG and HepB3 vaccines. These findings suggest that investment to strengthen the vaccine delivery system might improve timely vaccine uptake and equity in vaccine coverage.

Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.

Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients. The aim of this investigation was to determine whether transmural conduction gradients are modified in a rat model of pericardial adiposity. Adult Sprague-Dawley rats were fed control/high-fat diets for 15 wk. Left ventricular 300 µm tangential slices were generated from the endocardium to the epicardium, and conduction was mapped using microelectrode arrays. Slices were then histologically processed to assess fibrosis and cardiomyocyte lipid status. Conduction velocity was significantly greater in epicardial versus endocardial slices in control rats, supporting the concept of a transmural conduction gradient. High-fat diet feeding increased pericardial adiposity and abolished the transmural conduction gradient. Slowed epicardial conduction in epicardial slices strongly correlated with an increase in cardiomyocyte lipid content, but not fibrosis. The positive transmural conduction gradient reported here represents a physiological property of the ventricular activation sequence that likely protects against reentry. The absence of this gradient, secondary to conduction slowing and cardiomyocyte lipid accumulation, specifically in the epicardium, indicates a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.

Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype.

Activation of cardiac fibroblasts and differentiation to myofibroblasts underlies development of pathological cardiac fibrosis, leading to arrhythmias and heart failure. Myofibroblasts are characterised by increased α-smooth muscle actin (α-SMA) fibre expression, secretion of collagens and changes in proliferation. Transforming growth factor-beta (TGF-ß) and increased mechanical stress can initiate myofibroblast activation. Reversibility of the myofibroblast phenotype has been observed in murine cells but has not been explored in human cardiac fibroblasts. In this study, chronically activated adult primary human ventricular cardiac fibroblasts and human induced pluripotent stem cell derived cFbs (hiPSC-cFbs) were used to investigate the potential for reversal of the myofibroblast phenotype using either subculture on soft substrates or TGF-ß receptor inhibition. Culture on softer plates (25 or 2 kPa Young's modulus) did not alter proliferation or reduce expression of α-SMA and collagen 1. Similarly, culture of myofibroblasts in the presence of TGF-ß inhibitor did not reverse myofibroblasts back to a quiescent phenotype. Chronically activated hiPSC-cFbs also showed attenuated response to TGF-ß receptor inhibition and inability to reverse to quiescent fibroblast phenotype. Our data demonstrate substantial loss of TGF-ß signalling plasticity as well as a loss of feedback from the surrounding mechanical environment in chronically activated human myofibroblasts.

Ready, set, go! The role of organizational readiness to predict adoption of a family caregiver training program using the Rogers' diffusion of innovation theory.

BACKGROUND: Caregivers FIRST is an evidence-based program addressing gaps in caregivers' skills. In 2020, the Veterans Health Administration Caregiver Support Program (CSP) nationally endorsed Caregivers FIRST, offering credit in leadership performance plans to encourage all VA medical centers (VAMCs) to implement locally. This study examines the association of organizational readiness with VAMC adoption of Caregivers FIRST. METHODS: In a cohort observational study, we surveyed CSP managers about their facilities' readiness to implement using the Organizational Readiness for Implementing Change (ORIC) instrument and compared change commitment and change efficacy domains among VAMCs "adopters" defined as delivering Caregivers FIRST within 1 year of the national announcement to those that did not ("non-adopters"). Within "adopters," we categorized time to adoption based on Rogers' diffusion of innovation theory including "innovators," "early adopters," "early majority," "late adopters," and "laggards." Organizational readiness and site characteristics (facility complexity, staffing levels, volume of applications for caregiver assistance services) were compared between "adopters," "non-adopters," and between time to adoption subcategories. Separate logistic regression models were used to assess whether ORIC and site characteristics were associated with early adoption among "adopters." RESULTS: Fifty-one of 63 (81%) VAMCs with CSP manager survey respondents adopted Caregivers FIRST during the first year. ORIC change commitment and efficacy were similar for "adopters" and "non-adopters." However, sites that adopted earlier (innovators and early adopters) had higher ORIC change commitment and efficacy scores than the rest of the "adopters." Logistic regression results indicated that higher ORIC change commitment (odds ratio [OR] = 2.57; 95% confidence interval [CI], 1.11-5.95) and ORIC change efficacy (OR = 2.60; 95% CI, 1.12-6.03) scores were associated with increased odds that a VAMC was an early adopter (categorized as an "innovator," "early adopter", or "early majority"). Site-level characteristics were not associated with Caregivers FIRST early adoption. CONCLUSIONS: To our knowledge, this study is the first to prospectively assess organizational readiness and the timing of subsequent program adoption. Early adoption was associated with higher ORIC change commitment and change efficacy and not site-level characteristics. These findings yield insights into the role of organizational readiness to accelerate program adoption. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03474380. Registered on March 22, 2018.