Prophylaxis Research Articles

Allergy Modulation: Exploring the Role of Prebiotics, Probiotics, and Synbiotics in Enhancing Health Outcomes - A Literature Review

This literature review explores the role of prebiotics, probiotics, and synbiotics in the prevention and management of allergic diseases, including eczema, asthma, allergic rhinitis, and food allergies. The review delves into the mechanisms by which these dietary interventions modulate the gut microbiome, influence immune system responses, and enhance the epithelial barrier. While prebiotics promote the growth of beneficial gut bacteria and the production of short-chain fatty acids, probiotics introduce live microorganisms that restore balance in the gut ecosystem. Synbiotics combine both approaches to synergistically improve gut health. Despite the promising potential of these interventions, the evidence remains mixed, with their efficacy varying across different allergic conditions. This review underscores the need for further research to clarify the effectiveness of prebiotics, probiotics, and synbiotics in allergy prevention and management, highlighting the complexities involved in translating these findings into clinical practice.

Role of Vitamin D in Allergic Diseases

Introductions: Vitamin D has gained recognition in recent decades not only as a key regulator of calcium and phosphorus metabolism and bone health but also as an important factor modulating the immune system. Research indicates that vitamin D influences both innate and adaptive immune responses, which is significant in the treatment of allergic and inflammatory diseases. Vitamin D has a beneficial effect on asthma exacerbations and may help reduce respiratory inflammation, as well as alleviate symptoms of allergic rhinitis. Vitamin D deficiency may increase the risk of food allergies, worsen symptoms of atopic dermatitis, and contribute to the transition from acute to chronic urticaria. Conversely, supplementation may help prevent allergies, reduce the severity of atopic dermatitis by supporting skin barrier function and antimicrobial peptide production, and relieve symptoms in patients with chronic urticaria. Purpose of the study: The review article aims to present the current state of knowledge on the role of vitamin D in the treatment of asthma, allergic rhinitis, food allergies, atopic dermatitis, chronic urticaria, and eczema. Material and methods: To summarize the current knowledge on the topic, a literature review of English language papers with a focus on the most current literature was performed. The review was conducted with the PubMed database with 64 works used, accessed before October 2024. Conclusions: Although the impact of blood vitamin D levels on the development and progression of allergic diseases has not yet been fully clarified, scientific studies suggest its significant role in modulating immune responses. Due to its immunoregulatory properties, vitamin D offers new hope for more effective treatment and prevention of allergic diseases.

The Effect of Internet-Based Cardiac Rehabilitation on Anxiety, Depression, and Quality of Life Among Patients With Ischemic Heart Disease

Background Internet-based cardiac rehabilitation (IBCR) is an innovative, alternative platform used in current practice for the secondary prevention of ischemic heart disease (IHD). The impact of IBCR on anxiety, depression, and quality of life (QoL) in patients with IHD remains inconclusive. Objective To explore the effect of IBCR on anxiety, depression, and QoL among patients with IHD. Methods Five databases (Embase, CINAHL, Medline, Cochrane, and Web of Science) and additional resources were searched to identify studies published between January 2014 and March 2024. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Critical Appraisal Skills Program checklist were used. Two reviewers independently assessed study quality, eligibility, and data extraction. RevMan (version 5.3) software was used for the meta-analysis. The protocol was registered in PROSPERO (CRD42023387666). Results Thirteen randomized controlled trials were included across 9 countries. A total of 2256 participants, with a mean age ranging from 55 to 63 years, the majority being men (73%), were identified. IBCR did not significantly reduce anxiety (P = .22) or depression (P = .44) or increase QoL (P = .21) compared with usual care. Intervention was delivered mainly via smartphones. Physical activities and risk factor management were mostly used, and behavioral changes less likely occurred. Hospital Anxiety and Depression Scale was mostly used. Conclusions IBCR was comparable to the effects of usual care in cardiac rehabilitation. Theory-driven interventions with larger and diverse sample sizes, and longer durations across different regions, are recommended for reliable findings.

Abstract 4119941: Identification of individuals who benefit from omega-3 fatty acid supplementation to prevent coronary heart disease: A machine-learning analysis of the VITAL

Backgrounds: Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals would benefit the most from the supplementation. We sought to predict the individual treatment effect of omega-3 FA supplementation on CHD prevention and to develop an omega-3 effect score to stratify individuals according to their expected benefit from the supplementation. Methods: Among the 25,871 randomized participants without history of CVD in the VITamin D and OmegA-3 TriaL (VITAL), we applied machine-learning (ML) approaches to predict individual treatment effect of omega-3 FA supplementation on 5-year CHD risk (a composite of myocardial infarction, coronary revascularization, and CHD death) using 11 covariates pre-specified in the VITAL trial protocol. A 10-fold cross-validation was used and held-out test dataset was used for the evaluation. An omega-3 effect score was developed such that each covariate contributed linearly, and utility of the score was further evaluated by transportability analysis using the National Health and Nutrition Examination Survey (NHANES) data as the target population. Results: Omega-3 FA intervention led to absolute 0.48% [SE: 0.20] reduction in CHD in the total population. ML algorithms effectively stratified participants by their expected benefit according to individual factors; decreased CHD risk was observed in those with quintile 1 and 2 of the expected benefit (absolute CHD risk reduction %: 1.30 % [0.55] and 1.32 % [0.51] in quintile 1 and 2, respectively). Race, diabetes, and fish intake most contributed to the omega-3 effect score. CHD incidence rates per 1000 person-year were 5.5 [0.44] if treated and 8.5 [0.55] if not treated (35.3% reduction) in individuals with the score ≥11 (upper 40th percentile), and 3.9% [0.31] if treated and 3.4% [0.55] if not treated (14.7% increase) in those with the score <11, respectively. The transportability of the utility of the score to baseline NHANES data was confirmed. Conclusion: In VITAL, ML approaches identified individuals who experienced greater CHD reduction from the omega-3 FA intervention, and an omega-3 effect score stratified the expected benefit. Although it warrants testing in a new RCT, the omega-3 effect score holds promise for guiding the indication of omega-3 FA supplementation in US primary prevention population.

Abstract 4136403: Impact of Coronary Artery Calcium Scores on Cardiovascular Risk and Preventive Therapies: A Systematic Review and Meta-Analysis

Introduction: Coronary artery calcium (CAC) serves as a key marker of atherosclerosis and is widely utilized in the noninvasive evaluation of coronary artery disease. We aim to compare cardiovascular risk outcomes and the likelihood of initiating or continuing pharmacological and lifestyle preventive therapies in asymptomatic and symptomatic patients with a CAC score greater than zero and those with a CAC score of zero with no established diagnosis of coronary artery disease. Methods: We performed systematic searches of PubMed, Scopus, Google Scholar, Cochrane Central, and ClinicalTrials.gov from inception to May 2024. Our search focused on randomized controlled trials and observational studies comparing outcomes between patients with a CAC score greater than zero and those with a CAC score of zero. Results: We included 53 observational studies, incorporating data from 210,672 asymptomatic and 32,477 symptomatic patients. Over a mean follow-up duration of 8.6 years, we observed that a CAC score greater than zero significantly correlated with an elevated risk of major adverse cardiovascular events (MACE) (OR: 5.58; 95% CI: 4.05–7.69; P < 0.00001). This association extended to all-cause mortality (OR: 3.90; 95% CI: 2.78–5.48; P < 0.00001), myocardial infarction (OR: 4.01; 95% CI: 3.45–4.65; P < 0.00001), and the need for revascularization (OR: 11.90; 95% CI: 6.82–20.78; P < 0.00001). Patients with a CAC score greater than zero were more likely to commence and continue aspirin therapy (OR: 2.45; 95% CI: 1.56–3.83; P < 0.0001 for initiation and OR: 1.71; 95% CI: 1.31–2.23; P < 0.0001 for continuation). Similar trends were noted for lipid-lowering medications (OR: 2.44; 95% CI: 1.57–3.79; P < 0.0001 for initiation and OR: 2.48; 95% CI: 1.53–4.01; P = 0.0002 for continuation), as well as the initiation of blood pressure medications (OR: 1.94; 95% CI: 1.61–2.33; P < 0.00001). Furthermore, a CAC score greater than zero was linked to increased adoption of lifestyle modifications, including enhanced physical activity (OR: 1.84; 95% CI: 1.41–2.41; P < 0.00001) and dietary changes (OR: 1.94; 95% CI: 1.52–2.49; P < 0.00001). Conclusion: Patients with elevated CAC scores are more likely to initiate and continue preventive pharmacological therapies and adopt beneficial lifestyle modifications. These findings underscore the importance of CAC scoring in guiding the management and prevention of cardiovascular disease in both asymptomatic and symptomatic populations.

Symptomatic and Prophylactic Dantrolene Treatment in a Case of RYR1-Related Congenital Myopathy.

Symptomatic and Prophylactic Dantrolene Treatment in a Case of RYR1-Related Congenital Myopathy.

Trends in the Mortality and Death of Periviable Preterm Infants in the United States, 2011 to 2020.

This study aimed to examine the trends in the infant mortality rate (IMR) and the trends in the timing of death among periviable preterm infants at 22 to 24 weeks' gestational age (GA) in the United States from 2011 to 2020. Retrospective, serial cross-sectional analysis of periviable preterm infants born in the United States at 22 to 24 weeks' GA using the linked birth/infant death records from the Centers for Disease Control and Prevention. Data were analyzed from 2011 to 2020. The exposure was the year of death, and the outcome was the changes over time in the IMR and the timing of death. Further, we evaluated racial differences in the timing of death. We used nonparametric trend analysis to evaluate changes in mortality rate across the study period. The IMR was inversely related to GA, and for each GA and race/ethnicity, the IMR significantly declined during the study period. The IMR rate was highest in the first 7 days of life for all GAs and races/ethnicities. While Non-Hispanic White infants had a higher infant neonatal mortality rate than non-Hispanic Black infants, non-Hispanic Black infants had a higher postneonatal mortality rate. The IMR among periviable infants born at 22 to 24 weeks' GA improved for all GAs and races in the United States between 2011 and 2020. However, significant racial differences in the timing of death exist. · As expected, the IMR was inversely related to gestational age at 22 to 24 weeks.. · At each gestational age and for each racial/ethnic group, the overall IMR decreased during the study period.. · Non-Hispanic White infants had a higher neonatal mortality rate, whereas non-Hispanic Black infants had a higher postneonatal mortality rate..

Abstract 4120332: RISING TRENDS IN ISCHEMIC HEART DISEASE RELATED MORTALITY AMONG OLDER ADULTS WITH SLEEP APNEA IN THE UNITED STATES FROM 1999 TO 2021

Introduction: Sleep apnea (SA) is often underrecognized and undertreated despite its high prevalence in the adult population and its association with adverse cardiovascular outcomes. There are limited estimates of national trends on cardiovascular mortality in older patients with sleep apnea. We aimed to assess the sex and race-related trends of ischemic heart disease (IHD) mortality in the older adults with SA using a large population-based database. Methods: We utilized the Centers for Disease Control and Prevention Wide-Ranging, Online Data for Epidemiologic Research (CDC WONDER) database which provides information from death certificates of all US residents according to the International Classification of Diseases, Tenth Revision (ICD-10). The demographic and mortality data were obtained for the United States population >65 years from 1999 to 2021. Ischemic heart disease (ICD-10 codes I20-I25) was listed as the underlying cause of death, and SA (G47.3) as a contributing cause of death. Age adjusted mortality rates (AAMRs) per 1,000,000 population were calculated by standardizing deaths to the year 2000 US population. We used Jointpoint Regression Program to analyze temporal trends in mortality from 2000 to 2021. Average annual percentage change (AAPC) with 95% CI were calculated to examine trends in AAMR over time. Results: Overall, AAMR of IHD mortality for patients with SA increased from 7.9 per 1,000,000 (95% CI, 6.9-8.8) in 1999 to 53.4 per 1,000,000 (95% CI, 51.4-55.4) in 2021 with an AAPC of 9.1% per year (95% CI, 8.8-9.5). Men had consistently higher AAMR than women throughout the study period (overall AAMR men: 45.51 (95% CI, 44.8-46.2); women: 12.5 (95% CI, 12.2-12.8). Both the groups had a similar increasing trend in AAMR, with men having a steeper increase. [AAPC men: 9.3% (95% CI, 8.5-10.8) versus AAPC women: 8.6%, 95% CI, 8.1-9.7]. Non Hispanic (NH) White population had the greatest AAMR throughout the study period, followed by NH Black and Hispanic or Latino. The NH White population had the largest increase in AAMR from 1999 to 2021 (AAPC 9.4%, 95% CI:8.9-10.1). Conclusion: In the United States, there has been a general increase in IHD mortality related to sleep apnea over the last two decades. This rising trend as noted in our analysis is concerning and underscores the need for more robust cardiovascular surveillance in these patients.

Comparison and identification of human coronary plaques with/without erosion using patient-specific optical coherence tomography-based fluid-structure interaction models: a pilot study.

Plaque erosion (PE) with secondary thrombosis is one of the key mechanisms of acute coronary syndrome (ACS) which often leads to drastic cardiovascular events. Identification and prediction of PE are of fundamental significance for disease diagnosis, prevention and treatment. In vivo optical coherence tomography (OCT) data of eight eroded plaques and eight non-eroded plaques were acquired to construct three-dimensional fluid-structure interaction models and obtain plaque biomechanical conditions for investigation. Plaque stenosis severity, plaque burden, plaque wall stress (PWS) and strain (PWSn), flow shear stress (FSS), and ΔFSS (FSS variation in time) were extracted for comparison and prediction. A logistic regression model was used to predict plaque erosion. Our results indicated that the combination of mean PWS and mean ΔFSS gave best prediction (AUC = 0.866, 90% confidence interval (0.717, 1.0)). The best single predictor was max ΔFSS (AUC = 0.819, 90% confidence interval (0.624, 1.0)). The average of maximum FSS values from eroded plaques was 76% higher than that from the non-eroded plaques (127.96 vs. 72.69 dyn/cm2) while the average of mean FSS from erosion sites of the eight eroded plaques was 48.6% higher than that from sites without erosion (71.52 vs. 48.11 dyn/cm2). The average of mean PWS from plaques with erosion was 22.83% lower than that for plaques without erosion (83.2kPa vs. 107.8kPa). This pilot study suggested that combining plaque stress, strain and flow shear stress could help better identify patients with potential plaque erosion, enabling possible early intervention therapy. Further studies are needed to validate our findings.

Abstract 4117310: Alcohol-Related Cardiomyopathy - Exploration of Recent Mortality Trends in the United States

Introduction: Data is accumulating regarding the contemporary trends of mortality rates in patients with alcohol-related cardiomyopathy across the United States. Hypothesis: We hypothesized that with increased awareness about the adverse effects of alcohol on the cardiovascular system and the advancement of echocardiography in the early diagnosis of alcoholic cardiomyopathy, mortality rates may show a downward trend. Methods: This is a retrospective observational study that retrieved death certificates from the CDC WONDER (Center for Disease Control and Prevention’s Wide-ranging ONline Data for Epidemiological Research) database from 2001-2020. The mortality rate of alcohol-related cardiomyopathy using ICD code I42.6 (Alcoholic cardiomyopathy) was studied from 2001-2020. This study duration was further subdivided into five-year periods. We calculated the crude mortality rate and age-adjusted mortality rate per 100,000 for four U.S census regions (CR-1 Northeast, CR-2 Midwest, CR-3 South, CR-4 West). Results: The overall age-adjusted mortality rate remained at 0.1/100,000 deaths in four U.S census regions until 2015; however, in the last five years of the study period, AAMR(age-related mortality rate) increased from 0.1 to 0.2/100,000 deaths. Conclusions: The mortality trends associated with alcohol-related cardiomyopathy have not changed significantly over the past two decades. This can be explained by the larger number of people developing alcoholic cardiomyopathy due to the increase in global alcohol use in addition to the fact that more diagnosed patients are receiving earlier treatment with goal-directed medical therapy for cardiomyopathy. Limitations of this study include intrinsic weakness of the WONDER dataset (changes with ICD-9 to ICD-10 codes, and potentially miscoding) which needs further research. Discussion: This suggests that while mortality rates associated with alcohol-related cardiomyopathy remained relatively steady for most of the study period, there was a concerning uptick in the latter years. This could prompt further investigation into potential factors contributing to this increase, despite advancements in awareness and diagnostic techniques.

Abstract 4132212: Trends in Atrial Fibrillation or Flutter Related Mortality Among Adults in the United States: Insights from CDC WONDER Database from 1999-2020

Background: Atrial fibrillation or flutter (Afib/AFL) incidence rates continue to rise and are linked to significant mortality, particularly in older populations. Our analysis examines Afib/AFL mortality trends across different demographics and regions in the U.S. from 1999 to 2020, highlighting the importance of understanding these patterns. Aim: To guide preventive measures that alleviate the impact of Afib/AFL and identify high-risk populations and regions, we sought to quantify trends associated with Afib/AFL related mortality in the U.S. Methods: We conducted a comprehensive search of death certificates from 1999-2020 using Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database focusing on Afib/AFL mortality in adults with ICD-10 codes I48. Gender, race, geographical and urban-rural parameters were investigated by calculating annual percent change (APC) and age-adjusted mortality rates (AAMRs) per 100,000 persons using the Joinpoint Regression Program (Joinpoint V 4.9.0.0, National Cancer Institute). Results: A total of 2,581,488 deaths occurred in patients with Afib/AFL from 1999 to 2020. The AAMR displayed an abrupt rise from 2018 to 2020 (APC: 8.51; 95% CI: 4.84-10.47). Men consistently exhibited a higher AAMR (overall AAMR male: 79.4, 95% CI 79.3-79.6; female: 60.8, 95% CI 60.7-60.9). Non-metropolitan areas showed higher AAMRs than metropolitan areas (overall AAMR non-metropolitan areas: 74.9, 95% CI 74.7-75.1; metropolitan: 67.2, 95% CI 67.1-67.2). Disparities were also observed in AAMRs by region with the West region showing the highest mortality rate with a notable rise between 2010 and 2020 (APC: 3.70, 95% CI 3.30-5.37). Non-hispanic (NH) White population showed the highest mortality (overall AAMR: 74.2, 95% CI 74.1-74.3), followed by NH American Indian (AAMR: 50.3), NH Black (AAMR: 45.8), NH Asian (AAMR: 35.0) and Hispanic (AAMR: 37.9) populations. Conclusion: Mortality from Afib/AFL has risen from 1999 to 2020. Men, NH white populations, and residents in non-metropolitan areas and Western U.S. are at higher risk. Targeted interventions and strategic healthcare resource allocation are needed to address these disparities and improve outcomes.

Abstract 4138275: Demographic, Regional, and State-level Trends of Mortality in patients with Atrial fibrillation in the United States, 1999 to 2020

Background: There exists a paucity of data regarding mortality trends among individuals with atrial fibrillation (AF) based on age, gender, race and ethnicity, and geographic regions. Objective: To investigate the trends in mortality in the United States (US) associated with AF among individuals aged ≥45 years. Methods: We reviewed the death certificate data from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database to examine atrial fibrillation–related mortality trends from 1999 to 2020 in individuals ≥45 years of age. We calculated crude and age adjusted mortality rates (AAMRs) per 100 000 patients and annual percentage change (APC) with 95% CIs. Results: Between 1999 and 2020, 2,576,839 AF-related deaths were identified among US adults over 45 years of age. The age adjusted mortality rate (AAMR) for AF-related deaths rose significantly from 70.6 in 1999 to 149.1 in 2020. Initially, the AAMR remained stable from 1999 to 2009 (APC): 2.31; 95% CI: -0.57 to 5.84), then increased significantly from 2009 to 2018 (APC: 3.60; 95% CI: 2.12 to 4.75), and saw a sharp rise from 2018 to 2020 (APC: 8.46; 95% CI: 4.76 to 10.44). There were notable disparities among demographic groups. Men consistently had higher AAMRs than women from 1999 (men: 79.9, women: 64.4) to 2020 (men: 180.5, women: 125.3). Non-Hispanic (NH) White adults had the highest AAMR (108.6), followed by NH American Indian/Alaska Native (73.4), NH Black (66.7), Hispanic or Latino (55.5), and NH Asian or Pacific Islander adults (51.2). The age group 85+ consistently showed the highest mortality rates throughout the study period. Regional differences were also evident, with the residents of western region (109.5) and nonmetropolitan areas (109.6) having the higher AAMRs when compared to other regions (Midwest: 104.3, Northeast: 95.1, and South: 95.0) and metropolitan areas (98.3), respectively. State-level variations were also significant. Conclusion: Our study found a rise in AF-related mortality in the US from 1999 to 2020, with significant disparities among demographic and geographic subgroups. Higher AAMRs were noted in males, non-Hispanic Whites, adults over 85, and residents of the western and nonmetropolitan US. Addressing disparities in access to quality care, timely diagnosis, insurance maintenance, and implementing targeted health policies can help reduce AF-related mortality.

Abstract 4122048: Disparities in Heart Failure-Related Mortality Among Reproductive-Aged Women in the United States from 1999 to 2019

Introduction: Heart failure (HF) majorly affects the elderly, but can also affect the younger population. This study aims to examine the trends of HF-related deaths among reproductive-aged women in the United States (US). Method: We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, extracting data through ICD-10 codes I11, I13.0, I13.2, and I50 to find HF-related deaths among women aged 15-44 from 1999 to 2019. We examined demographic disparities in HF mortality rates over time, considering age, ethnicity, and geographic areas. Results were reported as age-adjusted mortality rate (AAMR) and 95% confidence interval (CI). Joinpoint regression assessed trend changes and annual percentage change (APC). Results: Between 1999 and 2019, a total of 43,683 women aged 15-44 died from HF in the US, with an AAMR of 3.5 per 100,000 (95% CI: 3.5-3.5). The AAMR increased from 2.6 in 1999 to 4.8 in 2019. Non-Hispanic Black women had the highest AAMR at 10.2, while Hispanics had the lowest at 1.8. Geographically, the South was the most affected region with an AAMR of 4.6, contributing to nearly half (48.9%) of all deaths. States including Massachusetts, Oregon, New Hampshire, and Minnesota had the lowest AAMRs. Rural areas showed a higher AAMR compared to urban areas (4.4 Vs. 3.3). The age group (35-44) accounted for the majority of deaths (73.7%). Conclusion: HF-related mortality among reproductive-aged women increased from 1999 to 2019, with the highest burden among non-Hispanic Black women and those in the Southern region. Enhancing access to care, particularly in rural areas, and implementing targeted prevention programs are vital to reducing mortality rates.

Abstract 4139135: Trends in Stroke Related Mortality in Atrial Fibrillation Patients Aged 25 and Older in the United States: Insights from the CDC WONDER Database

Background: Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This CDC analysis delves into mortality trends due to stroke in AF patients aged ≥ 25 years, from 1999 to 2020. By analyzing extensive datasets we scrutinized how factors such as gender, race, region of residence, and level of urbanization intersect with mortality rates. Methods: Death data from 1999 to 2020 was analyzed using the Centers for Disease Control and Prevention database, employing ICD codes I48 for AF and I64 for stroke. Age-adjusted mortality rate (AAMR) per 100,000 people with 95% confidence intervals was calculated for the total population, stratified by gender, race, urban/rural status, and census region. The Joinpoint regression software was used to calculate annual percentage change (APC) trend for each stratification. Results: In the U.S. between 1999 and 2020, total of 331,106 deaths occurred among adults due to AF associated with stroke. Deaths occurred predominantly in medical facilities (43.2%). The overall AAMR for AF associated stroke decreased from 26.8 per 100,000 in 1999 to 18.4 in 2020, with an AAPC of -2.05 (p value < 0.000001). Additionally, AAMR declined significantly from 1999 to 2018 (APC: -2.65, p value = 0.012398), followed by an increase from 2018 to 2020 (APC: 3.90, p value = 0.220356). Women had slightly higher AAMRs compared to men (men: 6.6; women: 7.1). The AAMR for women reduced substantially from 1999 to 2020 than for men. AAMRs varied among racial/ethnic groups, with White patients having the highest AAMR (7.4), followed by Blacks (5.4), American Indian or Alaska Natives (4.6), Asian or Pacific Islanders (4.5), and Hispanic population (4.1). AAMRs decreased for all races except for Black population. Geographically, AAMRs ranged from 4.3 in Nevada to 11.9 in Vermont, with the Western region showing the highest mortality (AAMR: 7.9). Nonmetropolitan areas had slightly higher AAMRs than metropolitan areas, with both experiencing a decrease over the study period. Conclusion: This analysis depicts significant disparities in mortality rates attributed to stroke associated with AF and underscores the need for larger population-based studies to further understand the primary factors influencing the observed geographical, racial, and gender differences. Targeted interventions and equitable healthcare access are crucial to mitigate these disparities and improve outcomes for this population.

Abstract 4131228: Where Adults with Advanced Heart Failure Die: Insights from the CDC-WONDER Database

Background: Adults with heart failure (HF) are becoming more and more prevalent. The location of death and related disparities in these patients are poorly understood. Aim: The purpose of the study was to look at the locations of adult deaths from HF and identify any age, race, or ethnicity-related variations over a 25-year period. Methods: The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Database provided death certificate data and the National Center for Health Statistics provided individual-level mortality data for the trend-level analysis of adults aged (20-64 and 65+ years) conducted from 1999-2023. Hospital, home, hospice and nursing home/long-term care were the categories for the places of death. Results: Between 1999 and 2023, a total of 7,644,759 adult deaths from HF were recorded (87.9% White, 53.4% female). HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities. Conclusion: Prioritize end-of-life planning for HF patients with poor prognosis, regardless of age, to improve quality of life and death.

Geo-classification of drug-resistant travel-associated Plasmodium falciparum using Pfs47 and Pfcpmp gene sequences (USA, 2018-2021).

Travel-related malaria is regularly encountered in the United States, and the U.S. Centers for Disease Control and Prevention (CDC) characterizes Plasmodium falciparum drug-resistance genotypes routinely for travel-related cases. An important aspect of antimalarial drug resistance is understanding its geographic distribution. However, specimens submitted to CDC laboratories may have missing, incomplete, or inaccurate travel data. To complement genotyping for drug-resistance markers Pfcrt, Pfmdr1, Pfk13, Pfdhps, Pfdhfr, and PfcytB at CDC, amplicons of Pfs47 and Pfcpmp are also sequenced as markers of geographic origin. Here, a bi-allele likelihood (BALK) classifier was trained using Pfs47 and Pfcpmp sequences from published P. falciparum genomes of known geographic origin to classify clinical genotypes to a continent. Among P. falciparum-positive blood samples received at CDC for drug-resistance genotyping from 2018 to 2021 (n = 380), 240 included a travel history with the submission materials, though 6 were excluded due to low sequence quality. Classifications obtained for the remaining 234 were compared to their travel histories. Classification results were over 96% congruent with reported travel for clinical samples, and with collection sites for field isolates. Among travel-related samples, only two incongruent results occurred; a specimen submitted citing Costa Rican travel classified to Africa, and a specimen with travel referencing Sierra Leone classified to Asia. Subsequently, the classifier was applied to specimens with unreported travel histories (n = 140; 5 were excluded due to low sequence quality). For the remaining 135 samples, geographic classification data were paired with results generated using CDC's Malaria Resistance Surveillance (MaRS) protocol, which detects single-nucleotide polymorphisms in and generates haplotypes for Pfcrt, Pfmdr1, Pfk13, Pfdhps, Pfdhfr, and PfcytB. Given the importance of understanding the geographic distribution of antimalarial drug resistance, this work will complement domestic surveillance efforts by expanding knowledge on the geographic origin of drug-resistant P. falciparum entering the USA.

Abstract 4120312: Patient Perspectives on Barriers and Facilitators to Familial Hypercholesterolemia Cascade Testing Through the Lens of the Socio-Ecological Model

Background: Low uptake of Familial Hypercholesterolemia (FH) cascade testing, the stepwise identification of at-risk relatives, leads to missed opportunities for atherosclerotic cardiovascular disease (ASCVD) prevention. The IMPACT-FH study offered strategies (packet, chatbot, and direct contact) to support FH cascade testing. Hypothesis: We hypothesized that IMPACT-FH strategies would facilitate cascade testing uptake and overcome persistent barriers to cascade testing. Aim: We aimed to understand barriers and facilitators to FH cascade testing in the context of the socio-ecological model (SEM) which provides a framework to examine the interconnected influences of intrapersonal, interpersonal, institutional, community, and policy levels. Methods: Semi-structured interviews were conducted with IMPACT-FH study participants. The SEM informed qualitative analysis to identify barriers and facilitators to FH cascade testing. Results: A total of 15 FH probands (initial family member tested) and 12 relatives were interviewed, of whom the majority (59%) were female with an average age of 55.7 years. All relatives completed cascade testing. At the interpersonal level, probands reported that relatives’ attitudes about high cholesterol, including seriousness and treatability, were a barrier or facilitator to cascade testing. Probands explained how relatives’ beliefs were informed by interactions with their clinicians and societal beliefs about cholesterol (i.e., medication stigma). Interpersonally, probands described challenges overcoming relatives’ beliefs and a reluctance to encourage relatives to complete testing despite the availability of novel strategies. Probands and relatives reported that insurance policies and concerns about testing costs informed cascade testing decision-making. Institutional strategies to provide low-cost testing and cost transparency were described as facilitators. Variable access to clinicians with genetics expertise and licensure laws were described as barriers by out-of-state relatives. Probands and relatives agreed that strategies providing direct access genetics expertise (i.e., direct contact, chatbot) helped address these barriers. Conclusion: The IMPACT-FH study ameliorated barriers at higher levels of the SEM related to access to genetics expertise and cost. Intra- and interpersonal barriers remained challenging to overcome. To improve FH detection and ASCVD prevention, it is important to address barriers at all levels of the SEM.

Abstract 4121359: Heart Disease and Heart Failure: Trends and Disparities in Mortality Rates in the United States from 2000 to 2020

Background: The remarkable decline in the overall prevalence and mortality rates of cardiovascular diseases (CVD) in the United States (US) over the past few decades has not been consistent across all age groups, sexes, races, and types of cardiovascular diseases. Heart disease (HD) and heart failure (HF) still pose a significant burden to the healthcare system. Objectives: This study sought to describe the age, sex and racial disparities in the trends in mortality rates for these two outcomes in the US over the past two decades. Methods: This was an ecological study with trend analysis of the mortality from heart disease and heart failure in the US between 2000 and 2020. Data on CVD was obtained from the National Centers for Disease Control and Prevention (CDC) surveillance databases and analyzed. Binomial regression models were used to evaluate trends in outcomes. Statistical significance was considered for p-values < 0.05. Results: There was a significant decrease in the age-standardized mortality for HD over the past two decades (from 343.5 per 100,000 cases to 215.1 per 100,000 cases (p<0.001)). Mortality rates were significantly higher in males (p<0.001, R2 = 0.92), non-Hispanic blacks (p<0.001) and non-Hispanic whites (p<0.001) compared to Hispanics, (R2 = 0.94) and in adults aged 65+ (p<0.001) and 75+ (p<0.001) (R2 = 0.98). There was no significant decrease in the age-standardized mortality for HF (from 26.9 per 100,000 cases to 25.7 per 100,000 cases (p=0.706)) due to a reversal in the trend after 2011. Though the rates were significantly lower in males overall (p=0.001, R2 = 0.27), these rates became higher in males and in non-Hispanic Blacks compared to non-Hispanic Whites beyond 2016. Mortality rates due to HF were highest in the 65+ and 75+ age groups. Conclusions: This study on national trends in heart disease and heart failure across age groups, sexes and races over the past two decades confirmed a significant reduction in heart disease mortality rates over this period, but with persistent disparities between males and females, non-Hispanic Blacks and other races and the older age groups. This study also highlights important reversals of heart failure mortality rates trends in more recent years in males and females, and non-Hispanic Blacks and Whites, the reasons for which are amenable to further research.

Abstract 4112716: The Trend In Racial Differences In Mortality Attributed To Congenital Heart Diseases In Infants In The United States From 2005 To 2019

Background: Deaths from congenital heart disease (CHD) in children have been decreasing in the United States. We examined the differences in mortality trends between Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) infants. Methods: We retrospectively analyzed publicly available data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). The data was obtained from the linked birth/infant deaths from 2005 to 2019. We evaluated all infant deaths up to 1 year of age with the cause of death listed as CHD (International classification of diseases, 10 th revision (ICD-10) codes Q20-Q26 (except atrial septal defect, Q21.1 and patent ductus arteriosus, Q25. CHD infant mortality rate (IMR) was calculated per 100,000 live births. Race was ascertained based on death certificate reporting. Joinpoint regression was used to examine CHD-IMR by year, including stratification by NHB vs NHW, and neonatal vs postneonatal. The difference between NHB and NHW CHD-IMR was ascertained via the Mann-Whitney U test. P<0.05 was considered statistically significant. Results: Out of 60,243,988 live births, there were 19,004 CHD-related infant deaths. The characteristics of the study population are displayed in Table 1. The overall CHD-IMR declined from 36.1 to 27.0 per 100,000 live births (25.2%) with an average annual percentage change (AAPC) of -2.1 [95% CI -2.6, -1.572] (Figure 1). The CHD-IMR was significantly higher in NHB than in NHW (40 vs 29.3; P<0.0001) and this difference remained when the mortality rate was stratified by neonatal and post-neonatal periods. The CHD-IMR decreased significantly in NHW [AAPC: -2%; 95% CI: -2.5, -1.5%], but not in NHB [AAPC of -1.4%, 95% CI, -3.0, 0.3%]. The NHB-to-NHW CHD-IMR ratio, a measure of CHD-IMR disparity averaged 1.4 over the study period [AAPC: 0.8%; 95% CI: -0.2, 1.8%] (Figure 2). Conclusions: The CHD-IMR declined significantly for NHW, but not in NHB in the US from 2005 to 2019. The CHD-IMR was higher in NHB than in NHW. There was no significant change in the NHB-to-NHW CHD-IMR ratio, signifying no change in the disparity that exists between NHB and NHW IMR. These findings may have implications for patient care and public health policymaking. They lay the groundwork for additional studies to determine and understand the drivers behind these findings such as in prenatal diagnosis.

D-limonene suppresses RANKL-induced osteoclast differentiation and promotes osteoblast activity in-vitro.

Treatments for osteoporosis are typically given post-fracture. Therefore, identifying safe prophylactic interventions to reduce fracture risk would be beneficial. One approach is to utilise the bioactive properties of natural compounds to modify osteoclast and osteoblast activity. D-limonene a well-tolerated, anti-inflammatory monoterpene found in citrus fruits holds promise due to its suppressive effect on NFκB, a key regulator of bone cell activity. We found that limonene promoted osteoblast differentiation and bone nodule formation and inhibited RANKL-indued osteoclast formation and bone resorption in-vitro. Limonene also reduced the pro-resorptive signal provided by osteoblast, augmenting markers of osteoblast differentiation (alkaline phosphatase, osterix and osteocalcin) and significantly decreased osteoclastogenic cytokine production (PTHrP, IL-1β and TNF-α). Therefore, limonene supplementation represents a potential route in combination with current interventions to optimise bone cell activity to maintain or enhance bone mass.