Activity-Dependent Degradation of the Nascentome by the Neuronal Membrane Proteasome.

Activity-dependent changes in neuronal function require coordinated regulation of the protein synthesis and protein degradation machinery to maintain protein homeostasis, critical for proper neuronal function. However, the biochemical evidence for this balance and coordination is largely lacking. Leveraging our recent discovery of a neuronal-specific 20S membrane proteasome complex (NMP), we began exploring how neuronal activity regulates its function. Here, we found that the NMP degrades exclusively a large fraction of ribosome-associated nascent polypeptides that are being newly synthesized during neuronal stimulation. Using deep-coverage and global mass spectrometry, we identified the nascent protein substrates of the NMP, which included products encoding immediate-early genes, such as c-Fos and Npas4. Intriguingly, we found that turnover of nascent polypeptides and not full-length proteins through the NMP occurred independent of canonical ubiquitylation pathways. We propose that these findings generally define a neuronal activity-induced protein homeostasis program of coordinated protein synthesis and degradation through the NMP.

Neuronal membrane proteasomes regulate neuronal circuit activity in vivo and are required for learning-induced behavioral plasticity.

Protein degradation is critical for brain function through processes that remain incompletely understood. Here, we investigated the in vivo function of the 20S neuronal membrane proteasome (NMP) in the brain of Xenopus laevis tadpoles. With biochemistry, immunohistochemistry, and electron microscopy, we demonstrated that NMPs are conserved in the tadpole brain and preferentially degrade neuronal activity-induced newly synthesized proteins in vivo. Using in vivo calcium imaging in the optic tectum, we showed that acute NMP inhibition rapidly increased spontaneous neuronal activity, resulting in hypersynchronization across tectal neurons. At the circuit level, inhibiting NMPs abolished learning-dependent improvement in visuomotor behavior in live animals and caused a significant deterioration in basal behavioral performance following visual training with enhanced visual experience. Our data provide in vivo characterization of NMP functions in the vertebrate nervous system and suggest that NMP-mediated degradation of activity-induced nascent proteins may serve as a homeostatic modulatory mechanism in neurons that is critical for regulating neuronal activity and experience-dependent circuit plasticity.

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation.

The mechanisms that promote excitatory synapse formation and maturation have been extensively studied. However, the molecular events that limit excitatory synapse development so that synapses form at the right time and place and in the correct numbers are less well understood. We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. The degradation of Ephexin5 promotes EphB-dependent excitatory synapse development and is mediated by Ube3A, a ubiquitin ligase that is mutated in the human cognitive disorder Angelman syndrome and duplicated in some forms of Autism Spectrum Disorders (ASDs). These findings suggest that aberrant EphB/Ephexin5 signaling during the development of synapses may contribute to the abnormal cognitive function that occurs in Angelman syndrome and, possibly, ASDs.

A historical, evidence-based, and narrative review on commonly used dietary supplements in lipid-lowering.

Dietary supplements augment the nutritional value of everyday food intake and originate from the historical practices of ancient Egyptian (Ebers papyrus), Chinese (Pen Ts'ao by Shen Nung), Indian (Ayurveda), Greek (Hippocrates), and Arabic herbalists. In modern-day medicine, the use of dietary supplements continues to increase in popularity with greater than 50% of the US population reporting taking supplements. To further compound this trend, many patients believe that dietary supplements are equally or more effective than evidence-based therapies for lipoprotein and lipid-lowering. Supplements such as red yeast rice, omega-3 fatty acids, garlic, cinnamon, plant sterols, and turmeric are marketed to and believed by consumers to promote "cholesterol health." However, these supplements are not subjected to the same manufacturing scrutiny by the Food and Drug Administration as pharmaceutical drugs and as such, the exact contents and level of ingredients in each of these may vary. Furthermore, supplements do not have to demonstrate efficacy or safety before being marketed. The holistic approach to lowering atherosclerotic cardiovascular disease risk makes dietary supplements an attractive option to many patients; however, their use should not come at the expense of established therapies with proven benefits. In this narrative review, we provide a historical and evidence-based approach to the use of some dietary supplements in lipoprotein and lipid-lowering and provide a framework for managing patient expectations.

Orthogonal approaches required to measure proteasome composition and activity in mammalian brain tissue.

Proteasomes are large macromolecular complexes with multiple distinct catalytic activities that are each vital to human brain health and disease. Despite their importance, standardized approaches to investigate proteasomes have not been universally adapted. Here, we describe pitfalls and define straightforward orthogonal biochemical approaches essential to measure and understand changes in proteasome composition and activity in the mammalian central nervous system. Through our experimentation in the mammalian brain, we determined an abundance of catalytically active proteasomes exist with and without a 19S cap(s), the regulatory particle essential for ubiquitin-dependent degradation. Moreover, we learned that in-cell measurements using activity-based probes (ABPs) are more sensitive in determining the available activity of the 20S proteasome without the 19S cap and in measuring individual catalytic subunit activities of each ß subunit within all neuronal proteasomes. Subsequently, applying these tools to human brain samples, we were surprised to find that post-mortem tissue retained little to no 19S-capped proteasome, regardless of age, sex, or disease state. In comparing brain tissues (parahippocampal gyrus) from patients with Alzheimer's disease (AD) and unaffected individuals, the available 20S proteasome activity was significantly elevated in severe cases of AD, an observation not previously noted. Taken together, our study establishes standardized approaches for the comprehensive investigation of proteasomes in mammalian brain tissue, and we reveal new insight into brain proteasome biology.

Digital Technologies in Cardiac Rehabilitation: A Science Advisory From the American Heart Association.

Cardiac rehabilitation has strong evidence of benefit across many cardiovascular conditions but is underused. Even for those patients who participate in cardiac rehabilitation, there is the potential to better support them in improving behaviors known to promote optimal cardiovascular health and in sustaining those behaviors over time. Digital technology has the potential to address many of the challenges of traditional center-based cardiac rehabilitation and to augment care delivery. This American Heart Association science advisory was assembled to guide the development and implementation of digital cardiac rehabilitation interventions that can be translated effectively into clinical care, improve health outcomes, and promote health equity. This advisory thus describes the individual digital components that can be delivered in isolation or as part of a larger cardiac rehabilitation telehealth program and highlights challenges and future directions for digital technology generally and when used in cardiac rehabilitation specifically. It is also intended to provide guidance to researchers reporting digital interventions and clinicians implementing these interventions in practice and to advance a framework for equity-centered digital health in cardiac rehabilitation.

A New Era in Cardiac Rehabilitation Delivery: Research Gaps, Questions, Strategies, and Priorities.

Cardiac rehabilitation (CR) is a guideline-recommended, multidisciplinary program of exercise training, risk factor management, and psychosocial counseling for people with cardiovascular disease (CVD) that is beneficial but underused and with substantial disparities in referral, access, and participation. The emergence of new virtual and remote delivery models has the potential to improve access to and participation in CR and ultimately improve outcomes for people with CVD. Although data suggest that new delivery models for CR have safety and efficacy similar to traditional in-person CR, questions remain regarding which participants are most likely to benefit from these models, how and where such programs should be delivered, and their effect on outcomes in diverse populations. In this review, we describe important gaps in evidence, identify relevant research questions, and propose strategies for addressing them. We highlight 4 research priorities: (1) including diverse populations in all CR research; (2) leveraging implementation methodologies to enhance equitable delivery of CR; (3) clarifying which populations are most likely to benefit from virtual and remote CR; and (4) comparing traditional in-person CR with virtual and remote CR in diverse populations using multicenter studies of important clinical, psychosocial, and cost-effectiveness outcomes that are relevant to patients, caregivers, providers, health systems, and payors. By framing these important questions, we hope to advance toward a goal of delivering high-quality CR to as many people as possible to improve outcomes in those with CVD.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Incidence and Outcomes of Posterior Circulation Involvement in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a progressive, occlusive disease of the internal carotid arteries and their proximal branches, with the subsequent development of an abnormal vascular network that is rupture-prone. Steno-occlusive changes in the posterior cerebral arteries (PCAs) may contribute to worsened outcomes in patients with MMD; however, there is little information on the incidence and natural history of posterior circulation MMD (PCMMD). We describe clinical PCMMD characteristics in a large cohort of patients with MMD. METHODS: We retrospectively reviewed patients with MMD treated between 1991 and 2019 at a large academic medical center. Demographics, perioperative outcomes, and radiological phenotypes were recorded for 770 patients. PCA disease was graded as either 0 (no disease), 1 (mild), 2 (moderate), or 3 (severe or occluded) based on cerebral angiography. Patients with angiographically confirmed MMD diagnosis with at least 6 months follow-up and completion of revascularization surgery were included; patients with intracranial atherosclerosis, intracranial dissection, vasculitis, and undefined inflammatory processes were excluded. The presence of stenosis/occlusion was graded radiographically to assess for disease progression and the prevalence of risk factors related to reduced progression-free survival. RESULTS: In all, 686 patients met the inclusion criteria, with PCA disease identified in 282 (41.1%) patients. Of those 282 patients with PCMMD, disease severity ranged from 99 (35.1%) with mild, 72 (25.5%) with moderate, and 111 (39.4%) with severe. The total number of postoperative complications was significantly associated with PCMMD severity (P=0.0067). Additionally, PCMMD severity correlated with worse postoperative modified Rankin Scale scores (P<0.0001). At a mean follow-up of 6.0±3.9 (range, 0.1-25.0) years, a total of 60 (12.6%) patients showed new/worsening PCMMD. The overall postoperative, progression-free survival in patients with PCMMD was 95.4% at 1 year, 82.4% at 3 years, 68.8% at 5 years, and 28.3% at 10 years, with prognostic factors for progression including preoperative PCMMD status, history of tobacco use, and hypertension (P<0.0001, P<0.001, and P<0.0001, respectively). CONCLUSIONS: PCA disease involvement in MMD is associated with higher rates of ischemic perioperative complications and worsened functional outcomes, likely due to reduced collateral flow. Ten-year progression of PCA disease is highly likely and should be monitored throughout follow-up; future studies will assess the impact of PCA disease progression on long-term outcomes.

Prevalence and Disparities in Telehealth Use Among US Adults Following the COVID-19 Pandemic: National Cross-Sectional Survey.

BACKGROUND: Telemedicine expanded during the COVID-19 pandemic, though use differed by age, sex, race or ethnicity, educational attainment, income, and location. It is unclear if high telehealth use or inequities persisted late into the pandemic. OBJECTIVE: This study aims to evaluate the prevalence of, inequities in, and primary reasons for telehealth visits a year after telemedicine expansion. METHODS: We used cross-sectional data from the 2022 Health Information National Trends Survey (HINTS 6), the first cycle with data on telemedicine. In total, 4830 English- and Spanish-speaking US adults (aged ≥18 years) were included in this study. The primary outcomes were telehealth visit attendance in the 12 months before March 7, 2022, to November 8, 2022, and the primary reason for the most recent telehealth visit. We evaluated sociodemographic and clinical predictors of telehealth visit attendance and the primary reason for the most recent telehealth visit through Poisson regression. Analyses were weighted according to HINTS 6 standards. RESULTS: We included 4830 participants (mean age 48.3, SD 17.5 years; 50.28% women; 65.21% White). Among US adults, 38.78% reported having a telehealth visit in the previous year. Telehealth visit attendance rates were similar across age, race or ethnicity, income, and urban versus rural location. However, individuals with a telehealth visit were less likely to live in the Midwest (adjusted prevalence ratio [aPR] 0.65, 95% CI 0.54-0.77), and more likely to be women (aPR 1.21, 95% CI 1.06-1.38), college graduates or postgraduates (aPR 1.24, 95% CI 1.05-1.46), covered by health insurance (aPR 1.56, 95% CI 1.08-2.26), and married or cohabitating (aPR 1.17, 95% CI 1.03-1.32), adjusting for sociodemographic characteristics, frequency of health care visits, and comorbidities. Among participants with a telehealth visit in the past year, the primary reasons for their most recent visit were minor or acute illness (32.15%), chronic disease management (21%), mental health or substance abuse (16.94%), and an annual exam (16.22%). Older adults were more likely to report that the primary reason for their most recent telehealth visit was for chronic disease management (aPR 2.08, 95% CI 1.33-3.23), but less likely to report that it was for a mental health or substance abuse issue (aPR 0.19, 95% CI 0.10-0.35), adjusting for sociodemographic characteristics and frequency of health care visits. CONCLUSIONS: Among US adults, telehealth visit attendance was high more than a year after telemedicine expansion and did not differ by age, race or ethnicity, income, or urban versus rural location. Telehealth could continue to be leveraged following COVID-19 to improve access to care and health equity.

Digital Health in Diabetes and Cardiovascular Disease.

BACKGROUND: Digital health technologies are rapidly evolving and transforming the care of diabetes and cardiovascular disease (CVD). PURPOSE OF THE REVIEW: In this review, we discuss emerging approaches incorporating digital health technologies to improve patient outcomes through a more continuous, accessible, proactive, and patient-centered approach. We discuss various mechanisms of potential benefit ranging from early detection to enhanced physiologic monitoring over time to helping shape important management decisions and engaging patients in their care. Furthermore, we discuss the potential for better individualization of management, which is particularly important in diseases with heterogeneous and complex manifestations, such as diabetes and cardiovascular disease. This narrative review explores ways to leverage digital health technology to better extend the reach of clinicians beyond the physical hospital and clinic spaces to address disparities in the diagnosis, treatment, and prevention of diabetes and cardiovascular disease. CONCLUSION: We are at the early stages of the shift to digital medicine, which holds substantial promise not only to improve patient outcomes but also to lower the costs of care. The review concludes by recognizing the challenges and limitations that need to be addressed for optimal implementation and impact. We present recommendations on how to navigate these challenges as well as goals and opportunities in utilizing digital health technology in the management of diabetes and prevention of adverse cardiovascular outcomes.

Lipid distributions in the Global Diagnostics Network across five continents.

AIMS: Lipids are central in the development of cardiovascular disease, and the present study aimed to characterize variation in lipid profiles across different countries to improve understanding of cardiovascular risk and opportunities for risk-reducing interventions. METHODS AND RESULTS: This first collaborative report of the Global Diagnostics Network (GDN) evaluated lipid distributions from nine laboratory organizations providing clinical laboratory testing in 17 countries on five continents. This cross-sectional study assessed aggregated lipid results from patients aged 20-89 years, tested at GDN laboratories, from 2018 through 2020. In addition to mean levels, the World Health Organization total cholesterol risk target (<5.00 mmol/L, <193 mg/dL) and proportions in guideline-based low-density lipoprotein cholesterol (LDL-C) categories were assessed. This study of 461 888 753 lipid results found wide variation by country/region, sex, and age. In most countries, total cholesterol and LDL-C peaked at 50-59 years in females and 40-49 years in males. Sex- and age-group adjusted mean total cholesterol levels ranged from 4.58 mmol/L (177.1 mg/dL) in the Republic of Korea to 5.40 mmol/L (208.8 mg/dL) in Austria. Mean total cholesterol levels exceeded the World Health Organization target in Japan, Australia, North Macedonia, Switzerland, Germany, Slovakia, and Austria. Considering LDL-C categories, North Macedonia had the highest proportions of LDL-C results >4.91 mmol/L (>190 mg/dL) for both females (9.9%) and males (8.7%). LDL-C levels <1.55 mmol/L (<60 mg/dL) were most common among females in Canada (10.7%) and males in the UK (17.3%). CONCLUSION: With nearly a half billion lipid results, this study sheds light on the worldwide variability in lipid levels, which may reflect inter-country differences in genetics, lipid testing, lifestyle habits, and pharmacologic treatment. Despite variability, elevated atherogenic lipid levels are a common global problem, and these results can help inform national policies and health system approaches to mitigate lipid-mediated risk of cardiovascular disease.

Satisfaction with Telehealth Care in the United States: Cross-Sectional Survey.

Background: Telehealth use remains high following the COVID-19 pandemic, but patient satisfaction with telehealth care is unclear. Methods: We used cross-sectional data from the Health Information National Trends Survey (HINTS 6). 2,058 English and Spanish-speaking U.S. adults (≥18 years) with a telehealth visit in the 12 months before March-November 2022 were included in this study. The primary outcomes were telehealth visit modality and satisfaction in the 12 months before HINTS 6. We evaluated sociodemographic predictors of telehealth visit modality and satisfaction via Poisson regression. Analyses were weighted according to HINTS standards. Results: We included 2,058 participants (48.4 ± 16.8 years; 57% women; 66% White), of which 70% had an audio-video and 30% an audio-only telehealth visit. Adults with an audio-video visit were more likely to have health insurance (adjusted prevalence ratio [aPR]: 1.55, 95% confidence interval [CI]: 1.18-2.04) and have an annual household income of ≥$75,000 (aPR: 1.18, 95% CI: 1.00-1.39) and less likely to be ≥65 years (aPR: 0.79, 95% CI: 0.70-0.89), adjusting for sociodemographic characteristics. No further inequities were noted by telehealth modality. Seventy-five percent of participants felt that their telehealth visits were as good as in-person care. No significant differences in telehealth satisfaction were observed across sociodemographic characteristics, telehealth modality, or the participants' primary reason for their most recent telehealth visit in adjusted analysis. Conclusions: Among U.S. adults with a telehealth visit, the majority had an audio-video visit and were satisfied with their care. Telehealth should continue, being offered following COVID-19, as it is uniformly valued by patients.

Interaction of preoperative chemoprophylaxis and tranexamic acid use does not affect transfusion in acetabular fracture surgery.

PURPOSE: While the effects of tranexamic acid (TXA) use on transfusion rates after acetabular fracture surgery are unclear, previous evidence suggests that holding deep vein thrombosis (DVT) chemoprophylaxis may improve TXA efficacy. This study examines whether holding DVT chemoprophylaxis in patients receiving TXA affects intraoperative and postoperative transfusion rates in acetabular fracture surgery. METHODS: We reviewed electronic medical records (EMR) of 305 patients who underwent open reduction and internal fixation of acetabular fractures (AO/OTA 62) and stratified patients per the following perioperative treatment: (1) no intraoperative TXA (noTXA), (2) intraoperative TXA and no preoperative DVT prophylaxis (opTXA/noDVTP), or (3) intraoperative TXA and preoperative DVT prophylaxis (opTXA/opDVTP). The primary outcomes were need for intraoperative or postoperative transfusion. Risk factors for each primary outcome were assessed using multivariable regression. RESULTS: Intraoperative or postoperative transfusion rates did not significantly differ between opTXA/opDVTP and opTXA/noDVTP groups (46.2% vs. 36%, p = 0.463; 15.4% vs. 28%, p = 0.181). Median units transfused did not differ between groups (2 ± 1 vs. 2 ± 1, p = 0.515; 2 ± 1 vs. 2 ± 0, p = 0.099). There was no association between preoperative DVT chemoprophylaxis and TXA with intraoperative or postoperative transfusions. EBL, preoperative hematocrit, and IV fluids were associated with intraoperative transfusions; age and Charlson Comorbidity Index (CCI) were associated with postoperative transfusions. CONCLUSION: Our findings suggest holding DVT prophylaxis did not alter the effect of TXA on blood loss or need for transfusion.

Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Prevalence of Polypharmacy in Patients With Vestibular and Balance Complaints.

OBJECTIVES: To determine the prevalence of polypharmacy in patients presenting with dizziness to a tertiary neurotology clinic and analyze the association between polypharmacy and clinical characteristics. DESIGN: Retrospective, cross-sectional review. Demographics, symptoms, diagnoses, medications, audiometry, dizziness handicap index (DHI) scores, and cognitive failure questionnaire (CFQ) scores were extracted from charts of patients seen as new patients from September 1, 2019, to March 31, 2020, with a primary complaint of dizziness. RESULTS: A total of 382 patients were included. More than two-thirds of the patients (n = 265, 69.4%) met criteria for polypharmacy (≥5 medications), of which most (n = 249, 94.0%) were prescribed a potentially ototoxic drug. Approximately 10% of patients were taking five or more ototoxic medications (oto-polypharmacy). Polypharmacy was correlated to age and was more common for patients with diabetes, hypertension, other cardiovascular comorbidities, and depression (odds ratio [OR], 3.73-6.67; p < 0.05). Polypharmacy was twice as likely in patients with mild to moderate hearing loss (OR 2.02 [1.24-3.29] and OR 2.13 [1.06-4.27], respectively; p < 0.05) and ~1.5× more likely in patients who had moderate to severe DHI scores (OR 1.65 [1.05-2.59] and OR 1.63 [1.00-2.65], respectively; p < 0.05). Patients with polypharmacy also had higher CFQ scores compared to those without polypharmacy (CFQ 32.5 [19.0-48.0] versus CFQ 25.0 [13.0-40.0]; p = 0.002. Oto-polypharmacy was more common for patients with lightheadedness as a dizziness descriptor (OR 3.16 [1.56-6.41]; p < 0.01). However, oto-polypharmacy was only more common for patients with mild to moderate hearing loss (OR 2.69 [1.33-5.45] and OR 2.86 [1.31-6.20], respectively; p < 0.01) and severe DHI scores (2.31 [1.12-4.77], p = 0.02). CONCLUSIONS: The prevalence of polypharmacy in patients with vestibular disorders is high. Some of the medications that patients are on are also potentially ototoxic at variable degrees. Polypharmacy is more common when lightheadedness is one of the dizziness descriptors and seems to be associated with worse scores on patient-reported outcome measures (DHI, CFQ). Medication reconciliation and multidisciplinary involvement could help to better address polypharmacy in this patient population. However, further investigation is needed to elucidate polypharmacy's role in symptom presentation, vestibular testing results, and therapeutic strategies.

Strategies for Improving Enrollment of Diverse Populations with a Focus on Lipid-Lowering Clinical Trials.

PURPOSE OF REVIEW: We review under-representation of key demographic groups in cardiovascular clinical trials, focusing on lipid-lowering trials. We outline multilevel strategies to recruit and retain diverse populations in cardiovascular trials. RECENT FINDINGS: Barriers to participation in trials occur at the study, participant, health system, sponsor, and policy level, requiring a multilevel approach to effectively increase participation of under-represented groups in research. Increasing the representation of marginalized and under-represented groups in leadership positions in clinical trials can ensure that their perspectives and experiences are considered. Trial design should prioritize patient- and community-indicated needs. Women and individuals from racially/ethnically diverse populations remain under-represented in lipid-lowering and other cardiovascular clinical trials relative to their disease burden in the population. This limits the generalizability of trial results to the broader population in clinical practice. Collaboration between community stakeholders, researchers, and community members can facilitate shared learning about trials and build trust.

Use of Human-Centered Design Methodology to Develop a Digital Toolkit to Optimize Heart Failure Guideline-Directed Medical Therapy.

BACKGROUND: Guideline-directed medical therapies (GDMTs) improve quality of life and health outcomes for patients with heart failure (HF). However, GDMT utilization is suboptimal among patients with HF. OBJECTIVE: The aims of this study were to engage key stakeholders in semistructured, virtual human-centered design sessions to identify challenges in GDMT optimization posthospitalization and inform the development of a digital toolkit aimed at optimizing HF GDMTs. METHODS: For the human-centered design sessions, we recruited (a) clinicians who care for patients with HF across 3 hospital systems, (b) patients with HF with reduced ejection fraction (ejection fraction ≤ 40%) discharged from the hospital within 30 days of enrollment, and (c) caregivers. All participants were 18 years or older, English speaking, with Internet access. RESULTS: A total of 10 clinicians (median age, 37 years [interquartile range, 35-41], 12 years [interquartile range, 10-14] of experience caring for patients with HF, 80% women, 50% White, 50% nurse practitioners) and three patients and one caregiver (median age 57 years [IQR: 53-60], 75% men, 50% Black, 75% married) were included. Five themes emerged from the clinician sessions on challenges to GDMT optimization (eg, barriers to patient buy-in). Six themes on challenges (eg, managing medications), 4 themes on motivators (eg, regaining independence), and 3 themes on facilitators (eg, social support) to HF management arose from the patient and caregiver sessions. CONCLUSIONS: The clinician, patient, and caregiver insights identified through human-centered design will inform a digital toolkit aimed at optimizing HF GDMTs, including a patient-facing smartphone application and clinician dashboard. This digital toolkit will be evaluated in a multicenter, clinical trial.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.