Citations

Abstract INTRODUCTION In the past decade, Jacksonville, Florida has seen an increase in African immigrants. However, little is known about their health needs and perspectives related to community health and clinical trials. The Mayo Clinic Comprehensive Cancer Center (MCCCC) Community Outreach and Engagement (COE) Office and Programs partnered with multiple community-based organizations as part of the FL Community Engagement Alliance Against COVID-19 to hold a series of focus groups with African immigrants to better understand their perspectives surroudning these determinants. METHODS This was a qualitative study with African immigrants residing in Jacksonville, Florida. Data was collected by community partner, Jocelyn Turner Consulting, who has led multiple community-based studies in Florida. Recruitment was in partnership with African businesses and churches. Using a guide developed by MCCCC COE, three focus groups were held to explore African immigrants’ 1) general experiences, 2) access to social services, 3) perspective of community health and diseases, 4) access and use of healthcare services, 5) knowledge and participation in clinical trials, and 6) appropriate strategies for providing community education and enhancing participation in research studies. RESULTS 24 participants participated in the focus groups. 83% had recently immigrated from Africa (Democratic of the Congo, Benin, Ghana, Sudan, Mali, Nigeria, Ethiopia, and Nigeria). The remaining 17% recently immigrated from Haiti or came to the US as a baby. Participants reported suprise to the proliferation of chronic diseases, such as increased cancer diagnoses of those who immigrated to the United States. Most participants associated this with the Western sedentary lifestyle, dietary habits, and lack of access to fresh food. Participants connected to refugee organizations reported knowledge of the ability to access health education resources and mental/physical care services, but those not connected with similar organizations expressed limited knowledge about access. Similarly, participants with no connection to refugee organizations reported not knowing where to access healthcare services and not seeking services until home remedies had failed. Only 33% of participants reported knowledge of clinical trials and all reported mistrust of research. Many of the participants expressed a need for health-related information upon arrival in the United States. CONCLUSION There is currently little infrastructure in place to support African immigrants in Jacksonville, Florida, which can contribute to cancer health disparities in this population. Strong community engagement is needed to partner with African immigrant communities to address culturally specific needs identified of this underrepresented population. The needs expressed by participants include information on physical activity, nutrition, and healthcare/clinical trials. A strong partnership with African immigrant communities has the potential to address cancer disparities and increase both trust and participation in clinical trials. Citation Format: Jocelyn Turner, Laureen Husband, Jessica Otero, Opeyemi Bolajoko, Parisa Fathi, Jennifer Crook, Folakemi Odedina. Perspectives of African immigrants on community health needs and clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A052.

Abstract Background: The National Comprehensive Cancer Network (NCCN) recommends the use of tissue-based genetic tests, such as Decipher, Prolaris, and Confirm mdx for localized prostate cancer, to help patients and caregivers make more informed treatment decisions at the time of diagnosis. However, while much enthusiasm currently exists for the burgeoning field of genomic medicine, prostate cancer disparities continue to persist in underserved communities despite the existence of evidence-based treatment guidelines. Methods: A diverse 15-member Community Advisory Board (CAB) representing rural and urban communities in Duval County, Florida were recruited from May to June 2023, to build a community-academic partnership, for the development and implementation of a genetic literacy patient-caregiver educational intervention for localized prostate cancer. The 15-member CAB was divided into groups of 5 for focus group discussions. Qualitative and quantitative data from CAB members were integrated to gain better understanding of the facilitators and barriers for prostate cancer genetic literacy in underserved communities. Results: The thematic analysis reveals several key themes related to prostate cancer, screening, treatment, and genetics. These themes reflect the diverse perspectives and experiences of the CAB members regarding prostate cancer, ranging from personal anecdotes to broader societal issues. Participants expressed thoughts related to fear, lack of knowledge, cultural beliefs, and access to healthcare. The discussion on prostate cancer and tissue based genetic testing highlighted the complexities surrounding prostate cancer and the need for further education, awareness, and access to affordable healthcare for all individuals at risk. Conclusion: CAB members emphasized the importance of improving access to information, promoting education, and addressing cultural barriers to ensure that individuals are informed about available options for prostate cancer diagnosis and treatment. Citation Format: Ewan K. Cobran, Jocelyn Turner, Folakemi Odedina, Alan H. Bryce, Christopher Williams, Jose Rodriguez, Roger Williams, Woodrow Nathan, Thomas Bryant III, LoveVonia Nathan, Laureen Husband. Community advisory board members’ perspectives on genetic literacy and patient-caregiver communication of prognostic genomics for localized prostate cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A042.

OBJECTIVE The aim of this study was to explore the preoperative patient characteristics that affect surgical decision-making when selecting an anterior or posterior operative approach in patients diagnosed with cervical spondylotic myelopathy (CSM). METHODS This was a multi-institutional, retrospective study of the prospective Quality Outcomes Database (QOD) Cervical Spondylotic Myelopathy module. Patients aged 18 years or older diagnosed with primary CSM who underwent multilevel (≥ 2-level) elective surgery were included. Demographics and baseline clinical characteristics were collected. RESULTS Of the 841 patients with CSM in the database, 492 (58.5%) underwent multilevel anterior surgery and 349 (41.5%) underwent multilevel posterior surgery. Surgeons more often performed a posterior surgical approach in older patients (mean 64.8 ± 10.6 vs 58.5 ± 11.1 years, p < 0.001) and those with a higher American Society of Anesthesiologists class (class III or IV: 52.4% vs 46.3%, p = 0.003), a higher rate of motor deficit (67.0% vs 58.7%, p = 0.014), worse myelopathy (mean modified Japanese Orthopaedic Association score 11.4 ± 3.1 vs 12.4 ± 2.6, p < 0.001), and more levels treated (4.3 ± 1.3 vs 2.4 ± 0.6, p < 0.001). On the other hand, surgeons more frequently performed an anterior surgical approach when patients were employed (47.2% vs 23.2%, p < 0.001) and had intervertebral disc herniation as an underlying pathology (30.7% vs 9.2%, p < 0.001). CONCLUSIONS The selection of approach for patients with CSM depends on patient demographics and symptomology. Posterior surgery was performed in patients who were older and had worse systemic disease, increased myelopathy, and greater levels of stenosis. Anterior surgery was more often performed in patients who were employed and had intervertebral disc herniation.

Introduction: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Goal: To identify serum proteins associated with risk for HF hospitalization (HFH) and cardiovascular (CV) death in patients with HFpEF, including proteins with differential associations with clinical outcomes in HFpEF compared to HFrEF. Methods: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF in the PARAGON-HF trial using a modified aptamer proteomic assay. Baseline protein concentrations significantly associated with total HFH and CV death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared to 2515 patients with HFrEF from the PARADIGM-HF and ATMOSPHERE trials. Results: We identified 288 proteins to be robustly associated with the risk of HFH and CV death (335 events over an average of 2.7 years of follow-up) in a HFpEF trial population. Proteins most strongly related to HFpEF outcomes included B2M, TIMP1, SERPINA4, and SVEP1 ( Figure ). Protein-outcome associations in patients with HFpEF did not markedly differ compared to HFrEF. Just 3 proteins (APOE, RTF1, and VWF) were differentially associated with outcomes between the HF subtypes (FDR <0.05). A proteomic risk score derived in HFpEF patients was not superior to a previous proteomic score derived in HFrEF nor to clinical risk factors, NT-proBNP, or high-sensitivity cardiac troponin. Conclusions: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis. SVEP1, a cell adhesion protein recently identified as a HFrEF prognosis biomarker, also strongly predicted risk in HFpEF. Our results demonstrate substantial similarities in serum proteomic risk markers across the EF spectrum.

OBJECTIVE There is a high prevalence of cervical myelopathy that requires surgery; as such, it is important to identify how different groups benefit from surgery. The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry, that includes demographic, clinical, and patient-reported outcome data to measure the safety and quality of neurosurgical procedures. In this study, the authors assessed the impact of gender on patient-reported outcomes in patients who underwent surgery for cervical myelopathy. METHODS The authors analyzed 1152 patients who underwent surgery for cervical myelopathy and were included in the QOD cervical module. Univariate comparison of baseline patient characteristics between males and females who underwent surgery for cervical spondylotic myelopathy was performed. Baseline characteristics that significantly differed between males and females were included in a multivariate generalized linear model comparing baseline and 1-year postoperative Neck Disability Index (NDI) scores. RESULTS This study included 546 females and 604 males. Females demonstrated significantly greater improvement in NDI score 1 year after surgery (p = 0.036). In addition to gender, the presence of axial neck pain and insurance status were also significantly predictive of improvement in NDI score after surgery (p = 0.0013 and p = 0.0058, respectively). CONCLUSIONS Females were more likely to benefit from surgery for cervical myelopathy compared with males. It is important to identify gender differences in postoperative outcomes after surgery in order to deliver more personalized and patient-centric care.

Abstract INTRODUCTION Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early‐onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS We analyzed MRI scans to define the sporadic EOAD‐signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early‐onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. RESULTS The EOAD‐signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD‐signature atrophy was associated with the severity of cognitive impairment. DISCUSSION The EOAD‐signature atrophy is a reliable and clinically valid biomarker of AD‐related neurodegeneration that could be used in clinical trials for EOAD. Highlights We developed an early‐onset Alzheimer's disease (EOAD)–signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD‐signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.

ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P &amp;lt; .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P &amp;lt; .001]; ADNI: t = 9.1 [P &amp;lt; .001]; HABS: t = 5.4 [P &amp;lt; .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P &amp;lt; .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

AbstractIn this overview, we describe important contributions from the Antibacterial Resistance Leadership Group (ARLG) to patient care, clinical trials design, and mentorship while outlining future priorities. The ARLG research agenda is focused on 3 key areas: gram-positive infections, gram-negative infections, and diagnostics. The ARLG has developed an innovative approach to clinical trials design, the desirability of outcome ranking (DOOR), which uses an ordinal measure of global outcome to assess both benefits and harms. DOOR was initially applied to observational studies to determine optimal dosing of vancomycin for methicillin-resistant Staphylcococcus aureus bacteremia and the efficacy of ceftazidime-avibactam versus colistin for the treatment of carbapenem-resistant Enterobacterales infection. DOOR is being successfully applied to the analysis of interventional trials and, in collaboration with the US Food and Drug Administration (FDA), for use in registrational trials. In the area of diagnostics, the ARLG developed Master Protocol for Evaluating Multiple Infection Diagnostics (MASTERMIND), an innovative design that allows simultaneous testing of multiple diagnostic platforms in a single study. This approach will be used to compare molecular assays for the identification of fluoroquinolone-resistant Neisseria gonorrhoeae (MASTER GC) and to compare rapid diagnostic tests for bloodstream infections. The ARLG has initiated a first-in-kind randomized, double-blind, placebo-controlled trial in participants with cystic fibrosis who are chronically colonized with Pseudomonas aeruginosa to assess the pharmacokinetics and antimicrobial activity of bacteriophage therapy. Finally, an engaged and highly trained workforce is critical for continued and future success against antimicrobial drug resistance. Thus, the ARLG has developed a robust mentoring program targeted to each stage of research training to attract and retain investigators in the field of antimicrobial resistance research.

AbstractIntroductionOne goal of the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40–64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants.MethodsLEADS amyloid‐positive early‐onset Alzheimer's disease (EOAD) or negative early‐onset non‐AD (EOnonAD) cases were whole exome sequenced (N = 299). Pathogenic variant frequency in APP, PSEN1, PSEN2, GRN, MAPT, and C9ORF72 was assessed for EOAD and EOnonAD. Gene burden testing was performed in cases compared to similar‐age cognitively normal controls in the Parkinson's Progression Markers Initiative (PPMI) study.ResultsPreviously reported pathogenic variants in the six genes were identified in 1.35% of EOAD (3/223) and 6.58% of EOnonAD (5/76). No genes showed enrichment for carriers of rare functional variants in LEADS cases.DiscussionResults suggest that LEADS is enriched for novel genetic causative variants, as previously reported variants are not observed in most cases.Highlights Sequencing identified eight cognitively impaired pathogenic variant carriers. Pathogenic variants were identified in PSEN1, GRN, MAPT, and C9ORF72. Rare variants were not enriched in APP, PSEN1/2, GRN, and MAPT. The Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) is a key resource for early‐onset Alzheimer's genetic research