Faculty Bibliography

INTRODUCTION/BACKGROUND:Family history of cardiovascular disease (CVD) is an independent risk factor for coronary heart disease, and the risk increases with number of family members affected. It offers insights into shared genetic, environmental and lifestyle factors that influence heart disease risk. In this study, we aimed to estimate the association of family history of CVD and its risk factors, as well as the number of affected parents or siblings, with the prevalence of major cardiometabolic risk factors (CRFs) such as hypertension, dysglycemia, dyslipidemia and obesity in a sample of young adults. METHODS:The study utilized a cross-sectional analysis of baseline data from the UAE Healthy Future Study (UAEHFS), involving 5,058 respondents below the age of 40 years. Information on parental and sibling health regarding heart disease and stroke, hypertension, type 2 diabetes (T2D), high cholesterol and obesity, was gathered through a self-completed questionnaire. CRFs were estimated based on body measurements, biochemical markers and self-reported conditions. Multivariate regression analyses were used to examine the associations between categories of family history and the estimated CRFs. RESULTS:More than half (58%) of the sample reported having a positive family history of CVD or its risk factors. The most common family history reported was T2D and hypertension, which accounted for 39.8% and 35% of the sample, respectively. The prevalence of all CRFs was significantly higher among those with a positive family history compared to those without family-history (P < 0.001). The prevalence and likelihood of having a CRF increased as the number of parents and/or siblings affected increased, indicating a potential dose-response trend. The odds were highest among individuals with both parental-and-sibling family history of disease, where they increased to 2.36 (95% CI 1.68-3.32) for hypertension, 2.59 (95% CI 1.86-3.60) for dysglycemia, 1.9 (95% CI 1.29-2.91) for dyslipidemia and 3.79 (95% CI 2.83-5.06) for obesity. CONCLUSION/CONCLUSIONS:In this study, we addressed the effect of family history as an independent risk factor on the major CRFs for the first time in the region. We observed that the majority of young Emirati adults had a positive family history of CVD-related diseases. Family history showed a strong association with the increased prevalence of CRFs. Additionally, having more relatives with specific diseases was associated with a higher risk of developing CRFs. Identifying people with a history of these conditions can help in early intervention and personalized risk assessments.

Maternal health and nutrition in early pregnancy play a vital role in the growth and development of the foetus. During this time, macro and micronutrients contribute to nutritional programming, which helps form the foundations of the foetus's life course health outcomes. This study aimed to investigate dietary habits, macro and micronutrient intake, micronutrient status, and folic acid supplement adherence among Emirati pregnant women in their first trimester. Data were collected according to the UAE-BCS study protocol, which was set up to investigate maternal nutrition, health, child growth, and developmental outcomes within the first 1000 days. Pregnant Emirati women with singleton pregnancies within their first trimester of pregnancy (between 8 and 12 weeks of gestation) were enrolled. The 24-hour food recall method was administered to collect dietary intake. The maternal mean average age was 29 years. Participants had high adherence to supplementation during pregnancy compared to preconception. The mean energy intake was 1345kcal, and 56% of participants consumed saturated fats above the acceptable macronutrient distribution ranges (AMDR), while 94% consumed below AMDR for total fibre. The consumption of micronutrients was below the recommended dietary allowance (RDA). Biochemical results show a high prevalence of low haemoglobin (74%) and deficiencies in vitamin D (39%) and vitamin E (96%). There is a need for research into dietary patterns and influences in pregnant women in the UAE. Furthermore, investigations of knowledge practices and attitudes towards supplementation and the factors contributing to folic acid supplement use are needed to inform government strategies and interventions.

BACKGROUND:Despite the proven efficacy of evidence-based healthcare interventions in reducing adverse outcomes and mortality associated with Sickle Cell Disease (SCD), a vast majority of affected individuals in Africa remain deprived of such care. Hydroxyurea (HU) utilization among SCD patients in Sub-Saharan Africa (SSA) stands at less than 1%, while in Nigeria, approximately 13% of patients benefit from HU therapy. To enhance HU utilization, targeted implementation strategies addressing provider-level barriers are imperative. Existing evidence underscores the significance of addressing barriers such as inadequate healthcare worker training to improve HU adoption. The ACCELERATE study aims to evaluate the adoption of HU among providers through the Screen, Initiate, and Maintain (SIM) intervention, facilitated by healthcare worker training, clinical reminders, and task-sharing strategies, thereby enhancing patient-level SCD management in Nigeria. METHODS:This study will implement the SIM intervention, encompassing patient screening, initiation of HU treatment, and maintenance of dosage, which will be implemented via the TAsk-Strengthening Strategy for Hemoglobinopathies (TASSH TCP), derived from our team's TAsk-Strengthening Strategy for Hypertension control (TASSH) trials. Employing a sequential exploratory mixed-methods approach within the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework, this study will assess SIM adoption by providers in Nigeria. The primary outcome is the rate of SIM adoption at clinical sites at 12 months, with secondary outcomes including sustainability/maintenance of SIM intervention and implementation fidelity. DISCUSSION/CONCLUSIONS:This study's findings will offer crucial insights into effective SCD management strategies, leveraging existing SCD clinical networks and resources in Nigeria to enhance HU adoption among providers in a scalable and sustainable manner. Additionally, the study will inform best practices for implementing HU therapy in resource-constrained settings, benefiting healthcare providers, policymakers, and stakeholders invested in improving SCD care delivery. TRIAL REGISTRATION/BACKGROUND:NCT06318143.

BACKGROUND/UNASSIGNED:Family history of substance use (FHSU), along with sociodemographic and psychosocial factors, has been identified as a key risk factor for adolescent substance use and progression to substance use disorders (SUD). However, the interaction between distinct sociodemographic and psychosocial profiles in adolescents with FHSU and constitutional factors, such as psychopathological symptom severity, impulsivity, and reward processing, remains unclear. Given the complexity of these factors, it is crucial to explore how these elements contribute to the differential vulnerability to SUD among youth with family history of substance use. Particularly as, the identification of clinically relevant subgroups of at-risk youth may inform precision prevention and treatment approaches to reduce adverse outcomes related to SUDs. METHODS/UNASSIGNED: = 4,369; female 48.33%, White 61.16%), respectively]. We used K-means clustering to identify latent subgroups in the FHSU-P population based on psychosocial variables and then compared the resulting subgroups on internalizing, externalizing, and total psychopathology, impulsivity, and reward prediction errors. RESULTS/UNASSIGNED: = 443) were characterized by lower engagement across peer, school, and parental domains. Group comparisons showed that Subgroups 1 and 2 had comparable levels of psychopathology and impulsivity, while Subgroups 3, 4, and 5 displayed higher psychopathology and impulsivity. Reward prediction errors were similar across all subgroups. Other group differences are also presented and discussed in the main text. CONCLUSION/UNASSIGNED:These findings highlight significant heterogeneity within the FHSU-P group and emphasize the importance of stratifying adolescents based on sociodemographic and psychosocial factors. Such stratification can help identify adolescents at higher risk for psychopathologies, including SUDs, offering insights for targeted prevention and intervention strategies.

BACKGROUND/UNASSIGNED:Magnetic resonance imaging (MRI) and electroencephalography (EEG) are valuable tools for studying neuroanatomical and electrophysiological features of early brain development. Studies implementing neuroimaging tools in low- and middle-income countries are still rare, and there is limited data on the acceptability of such tools among rural communities. The present study explores the perceptions, feasibility, and acceptability of introducing MRI and EEG for child development research in the rural Amhara region of Ethiopia. METHODS/UNASSIGNED:= 16). A semi-structured interview included four themes: (1) Baseline imaging knowledge, (2) Perceptions of MRI and EEG, (3) Facilitators and barriers to acceptability of MRI and EEG, and (4) Recommendations to improve MRI and EEG uptake. Interviews were conducted in Amharic, the local language. All interviews were transcribed verbatim to Amharic, translated into English, and double-coded. We used thematic analysis to organize data according to predefined and emerging themes. RESULTS/UNASSIGNED:Knowledge of MRI and EEG was limited, and none of the community members had previous experiences with either technology. Broadly, participants responded positively to our introductory videos showing MRI and EEG acquisition and expressed high levels of acceptability. However, participants reported concerns about possible harms related to radiation, electrical shock, and injury from MRI/EEG procedures. Those with lesser education were identified to be less accepting of MRI/EEG. In addition, several mothers expressed that consent from their husbands was necessary for their child's participation in neurodevelopmental research. Potential logistical barriers identified included transportation challenges to the neuroimaging study sites, especially for rural-dwelling families. Creating awareness, using explanatory videos, and engaging community members and clinicians were recommended to facilitate acceptance of EEG and MRI. CONCLUSION/UNASSIGNED:In this formative study, MRI and EEG were viewed as acceptable methods for assessing child neurodevelopment in rural areas of Ethiopia. Community members' and clinicians' views were impacted largely by social, religious, educational, and logistical aspects. Concerns related to MRI radiation, electrical shock, and injuries from EEG can be addressed through awareness creation and education. Engaging community leaders and healthcare providers is key to improving acceptability.

PURPOSE/OBJECTIVE:To determine the robustness of randomized controlled trials (RCTs) supporting the current rhinosinusitis guideline; International Consensus Statement on Allergy and Rhinology: rhinosinusitis (ICAR-RS). MATERIALS & METHODS/METHODS:RCTs referenced by ICAR-RS with primary dichotomous outcomes were analyzed. The Fragility Index (FI) was calculated for trials with statistically significant findings. Trial characteristics, the FI, and FI minus number lost to follow-up (LTF) were assessed for associations. RESULTS:A total of 317 RCTs were identified, with 38 trials possessing a primary dichotomous outcome. Thirty-one percent evaluated surgical interventions and 24 % were industry-sponsored. The mean sample size was 116 with 9 patients, on average, LTF. Sixty-three percent were eligible for FI calculation and had a median FI of 2.5 (IQR 1, 4.25). Sixty-seven percent of trials had an FI ≤ 3, indicating low robustness. No difference in FI was observed between trials with and without industry support (p = 0.577). The FI was less than or equal to the number of patients LTF in 33 % of trials (n = 8). Higher FI was strongly correlated with higher sample size, total number of events, p-value, and grade of recommendation (p < 0.001). After adjusting for covariates, higher sample size and total number of events were associated with higher FI. CONCLUSION/CONCLUSIONS:The RCTs used to support the ICAR-RS have an overall low robustness and future rhinosinusitis trials should report FI measures to provide improved context of their results.

BACKGROUND/UNASSIGNED:Transgender women of color in the US are disproportionately vulnerable to HIV risks. Pre-Exposure Prophylaxis (PrEP) has demonstrated effectiveness in preventing HIV transmission among transgender women of color. However, factors across multiple levels can hinder oral PrEP adherence. METHODS/UNASSIGNED:We analyzed the baseline data from The Trying to Understand Neighborhoods and Networks Among Transgender Women of Color (TURNNT) Cohort Study of women not living with HIV. We analyzed questionnaire responses to identify why participants stopped using PrEP and if they would consider taking it again. To identify multi-level determinants that were associated with PrEP discontinuation, we conducted bivariate analysis and created multivariable modified Poisson models comparing factors between former users and current users. RESULTS/UNASSIGNED:Among 140 transgender women of color included in this analysis, 44.3% were currently on PrEP, 25.0% were on formerly on the regimen, and 30.7% had never used it. Participants reported many reasons for discontinuing PrEP, notably, 22.9% reported being concerned about interactions with hormones. 60.0% reported that they were likely to take PrEP again in the future. Discontinuation was positively associated with history of sexual assault (Prevalence Ratio: 1.78; 95% CI: 1.01, 3.14) and negatively with having a primary care provider (PR: 0.43; 95% CI: 0.25, 0.73). CONCLUSION/UNASSIGNED:Many factors can influence PrEP discontinuation among transgender women of color. A majority of those who discontinued PrEP were interested in restarting it again, indicating a potential for reengagement. We recommend a holistic approach to HIV prevention to reduce PrEP discontinuation.

Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45-74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45-74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

Alzheimer's disease rates are expected to triple by 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming increase. Physical function index (PFI) declines with age; additionally, higher PFI is associated with better cognitive functioning in middle-to-older age individuals. However, most studies utilize one domain of PFI to examine associations with cognition. Therefore, using clustering methods, the purpose of this investigation was to determine if high-risk individuals with higher PFI have better cognitive outcomes compared to individuals with lower PFI. Participants (n = 215; 73.1% female; 45-75 years) completed a body mass scan, venous blood draw, 7 PFI tasks, and 7 cognitive tests. A k-means cluster analysis was utilized to identify PFI cluster for participants, one-way ANCOVAs were used to assess differences in cognition among clusters. Cluster 1 (C1; n = 29) was characterized as the highest strength/power, faster dual-task walking time, and higher aerobic capacity, Cluster 3 (C3; n = 113) had the lowest values between PFI groups, Cluster 2 (C3; n = 74) was in-between C1 and C3. Individuals in C1 had significantly higher global cognitive, visuospatial scores, digital executive functioning and associative learning compared to individuals in C3 (p < 0.05). Individuals in C1 and C2 had significantly higher values on orientation task and figure recall than individuals in C3 (p < 0.05). The results from this current study demonstrate that individuals with higher combined PFI output have higher global cognitive scores than individuals with lower combined PFI output. Examining PFI variables together may be a valuable tool when assessing cognition among cognitively at-risk individuals.