Citations

Introduction: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy affecting populations across the United States. Several well-established patient-centered comprehensive care models have been in practice for preventive care and pain management. However, access to hematopoietic stem cell transplant (HSCT) and clinical trials for sickle cell gene therapies are limited, especially in pediatric and adult centers with limited HSCT-related resources. We describe a patient-centered collaborative model in the Upper Midwest United States to improve patient education and engagement as well as access to HSCT and gene therapy trials for patients with SCD. Collaborative Care Model: Since August 2021, centers across the Midwest meet monthly to improve access for HSCT and gene therapy as well as education about these therapies for individuals with SCD. The teams include: hematology and transplant teams from University of Minnesota, Comprehensive Sickle Cell Care team from Children's Hospital of Minneapolis, hematology and transplant team from Mayo Children's Hospital, hematology team from Essential Health, Duluth, Minnesota, hematology team from Sanford Children's Hospital Fargo and Sioux Falls and hematology team from Blank Children's Hospital, Des Moines, Iowa. This collaborative approach involves several stakeholders including an SCD community advocacy organization, hematology care providers across several rural as well as community/university hospitals, social workers, nurse coordinators, HSCT/gene therapy providers, as well as representatives from National Marrow Donor Program. Individual patient needs and available community support as well as institutional resources are discussed at length during monthly virtual meetings and a pre-intervention plan is established to ensure smooth transition of care to and from primary centers (Figure 1). Ongoing communication with the primary team helps with efficient transition of care after transplant as patients continue ongoing monitoring and care closer to home. Community partners help with early education of the families and provide necessary resources and support. Institutional partners like NMDP provide support with immune typing and discuss ongoing support and other resources available for providers and families. Results/Impact: Since the implementation of this collaborative model, there has been a steady increase in early referrals for education regarding HSCT and potential gene therapies trials for patients with SCD. There has been about 100% increase in new patient referrals since the implementation of this collaborative model compared to the average new referrals in the previous years (2021-22 vs 2018-19; Figure 2). Enrollment in HSCT as well as gene therapy clinical trials also has increased 2-3 folds since the implementation of the collaborative care model. It has helped established early discussion and longitudinal care and has also led to ongoing evaluation and discussions for availability of optimal donors, determining eligibility for HSCT and gene therapy trials as well as providing ongoing support and education to the sickle cell community and providers regarding the available therapies for SCD. This has also facilitated the transplant team establish earlier and better rapport with patients and their families and provide necessary education with an in-depth discussion regarding the potential benefits and risks of therapies such as HSCT and gene therapy. These discussions often occur over multiple visits and helps address psychological as well social barriers with a prospective evaluation. Additionally, the ongoing discussion among the providers helps with longitudinal monitoring of the patients and provide an assessment of the risks and benefits of therapies as the patient's disease course continues to evolve. This multi-stake holder collaborative approach continues to provide a well-established platform for discussion of newer therapies and access to open clinical trials, available resources for patients and families, and improve patient care and experience. The impact of this collaboration is noted in significant increase in early referrals and educational consults for HSCT and gene therapies, improved patient engagement as well as the acceptability and participation in clinical trials.

Abstract Background: The increasing number of African immigrants in the United States has contributed to the diversity of the country's Black population. However, there is limited research on the impact of immigration, particularly regarding chronic diseases like cancer, within the sub-Saharan African immigrant (SSAI) community. To address this gap, this study aimed to explore cultural factors among SSAIs to better understand the drivers of health disparities in prostate cancer outcomes. Methods: A qualitative approach using grounded theory was employed for this study. Participants were purposefully recruited to reflect the cultural diversity among SSAIs. Recruitment occurred at health fairs, community events and by snowball approach. In-depth interviews were conducted with 16 participants, including prostate cancer survivors. Nine participants have lived in the US for at least 10 years. The average age of participants was 51 years. Country of birth for study participants include, Nigeria, Ghana, Cameroon, Kenya, and Ethiopia. Interviews were transcribed, verified, and de-identified then imported into NVivo 12 software. Four research team members, three of them African immigrants, performed open and axial coding, with consensus on the emerging findings. Results: This study identified several key cultural factors influencing SSAI men’s health behaviors. These factors include the perception of cancer in their country of birth, the low priority given to preventative care in their country of origin, and reluctance to embrace a Westernized diet, the perception of cancer in their country of origin as a death sentence, viewing cancer as a spiritual/religious attack, and associating cancer with affluence. In addition, these cultural factors made participants hesitant to discuss cancer, relying on religion for healing instead of medical care, and seeking healthcare only for cure. Conclusion: This study illuminates key cultural factors among SSAI men that influence their health-seeking behaviors. These findings highlight the need for culturally tailored behavioral interventions to address these factors and improve health outcomes within this understudied population. Citation Format: Ernest Kaninjing, Motolani Ogunsanya, Kaitlin Van Voorhis, Gladys Asiedu, Assata Kokayi, Rae Walker Brennan, Mary Ellen Young, Folake Odedina. The influence of cultural factors on health-seeking behaviors regarding prostate cancer among African immigrant men in the United States [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 A070.

Abstract Background: Sub-Saharan African immigrant (SSAI) men constitute one of the fastest-growing immigrant populations in the United States and a large heterogeneous group in cancer survivorship. Yet research has ignored decision making about health and behavioral risk factors among SSAI communities. Intersecting acculturation and culture-specific perceptions about cancer screening within decision-making frameworks may be an essential step towards developing meaningful interventions for immigrant men’s healthcare. Objectives: This study aimed to gain insight into cancer-related beliefs and health decision-making practices among sub-Saharan African immigrant men. Methods: A qualitative design intersecting grounded theory analysis was employed using 16 semi-structured, in-depth individual interviews with SSAI men residing in Georgia and Florida. Participants were recruited from health fairs, community events, and by snowball effect. The average age of participants was 51 years with country of birth including Cameroon, Ethiopia, Ghana, Kenya, and Nigeria. An interview guide was prepared with emphasis on SSAI’s perspectives on lifestyle factors for cancer and decision making about cancer screening. Data were audio-recorded, transcribed, and analyzed using open, inductive, and axial coding via NVivo 12 qualitative data analysis software. Results: Findings identified key cultural factors impacting barriers to and facilitators of SSAI men’s decision-making processes and health-seeking behaviors. Most participants making positive decisions reflected on intercultural health practices made in collaboration with clinicians, significant others and community partnerships. Most participants with negative decisions tended to consider socio-cultural barriers and shortcomings in US health-care system. Participants’ preventative care decisions about cancer screening differed. Conclusions: This qualitative study illuminated key cultural factors among SSAI men that influenced their decision making about cancer screening and health-seeking behaviors. Future research should investigate longitudinal and quantitative studies to test decision-making outcomes. Funding Source: This study is funded by the National Institute on Minority Health and Health Disparities (1R15MD017012-01A1). Keywords: Cancer health disparities, Decision-making, Immigrant men, Intersectionality, Qualitative study Citation Format: Assata Kokayi, Gladys Asiedu, Kaitlin Van Voorhis, Rae Walker, M.E. Young, Folakemi Odedina, Motolani Ogunsanya, Ernie Kaninjing. Intersecting acculturation and decision making about cancer screening among sub-Saharan African immigrant men: A qualitative study [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 A062.

AbstractIntroductionStudies have reported a higher risk of suboptimal neurodevelopment among children who are HIV‐exposed uninfected (HEU) compared to children HIV‐unexposed uninfected (HUU). Actual academic performance among school‐aged children by HIV exposure status has not been studied.MethodsAcademic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana‐based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran‐Mantel‐Haenszel test. Lower academic performance was defined as a grade of “C” or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance.ResultsBetween April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9–10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three‐drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]).ConclusionsIn this Botswana‐based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio‐demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.

AbstractBackgroundP2X purinoceptor 7 (P2RX7), an ATP‐gated cation channel present abundantly in the microglia, induces membrane depolarization and extracellular vesicle (EV) secretion. Previous study demonstrated that administration of GSK1482160, a P2RX7 selective inhibitor, suppressed EVs secretion from murine microglia resulting in accumulation of Tsg101+ intraluminal vesicles (ILVs) in the hippocampus, and restored partial behavioral deficits in P301S tau mice. However, the specificity of GSK1482160 to P2RX7 has never been investigated in P301S tau mice. It is crucial to validate whether P2RX7 is a potential target for alleviating the tauopathy phenotype in P301S tau mice. The purpose of this study is to determine if deletion of P2RX7 is sufficient to recapiturate the therapeutic effect of GSK1482160 in tauopathy mouse model.MethodFours and nine‐months‐old P2RX7‐/‐:P301S and P301S mice were generated for the evaluation of ILV accumulation and tau pathology. Primary microglia and astrocytes from WT (C57BL/6) and P2RX7‐/‐ mice, treated with GSK1482160 and ATP for EV secretion. EVs were isolated from conditioned media via the sequential centrifugation and ultracentrifugation. Finally, EVs were quantified by nanoparticle tracking analysis and exosome specific marker CD9 ELISA. Effects of GSK1482160 on EVs secretion from astrocytes/microglia were also assessed using Western blot with EV specific markers Tsg101 and CD9.ResultExosome specific marker Tsg101, CD9, and tau expression levels were reduced in the hippocampus of nine‐months‐old P2RX7‐/‐:P301S mice compared to P301S mice. No significant difference between the two groups at 4 months of age was observed. Strikingly, primary cultured microglia and astrocytes showed reduction in EV secretion in both ATP stimulated or unstimulated condition from P2RX7‐/‐ group compared to WT group. Additionally, GSK1482160 pretreatment significantly reduced EV secretion from WT astrocytes and microglia, although it had no effects in P2RX7‐/‐ cells. These findings were validated by ELISA of EV marker CD9 and immunoblotting of Tsg101 and flotillin‐1 using isolated EVs.ConclusionResults demonstrate that P2RX7 is primarily responsible for ATP‐induced EV secretion from astrocytes and microglia, and systemic disruption of P2RX7 mimics the effect of GSK1482160 in P301S tau mice, including accumulation of ILVs in microglia and suppression of tau accumulation in the hippocampal regions.

ObjectiveThe study objective was to identify differences in gene expression between treatment responders (TRs) and treatment non‐responders (TNRs) diagnosed with juvenile dermatomyositis (JDM).MethodsGene expression analyses were performed using whole blood messenger RNA sequencing in patients with JDM (n = 17) and healthy controls (HCs; n = 10). Four analyses were performed (A1‐4) comparing differential gene expression and pathways analysis exploiting the timing of sample acquisition and the treatments received to perform these comparative analyses. Analyses were done at diagnosis and follow‐up, which averaged 7 months later in the cohort.ResultsAt diagnosis, the expression of 10 genes differed between TRs and TNRs. Hallmark and canonical pathway analysis revealed 11 and 60 pathways enriched in TRs and 3 and 21 pathways enriched in TNRs, respectively. Pathway enrichment at diagnosis in TRs was strongest in pathways involved in metabolism, complement activation, and cell signaling as mediated by IL‐8, p38/microtubule associated protein kinases (MAPK)/extracellular signal‐regulated kinases (ERK), Phosphatidylinositol 3 Kinase Gamma (PI3Kγ), and the B cell receptor. Follow‐up hallmark and canonical pathway analysis showed that 2 and 14 pathways were enriched in TRs, whereas 24 and 123 pathways were enriched in treatment TNRs, respectively. Prior treatment with glucocorticoids significantly altered expression of 13 genes in the analysis of subjects at diagnosis with JDM as compared with HCs.ConclusionNumerous genes and pathways differ between TRs and TNRs at diagnosis and follow‐up. Prior treatment with glucocorticoids prior to specimen acquisition had a small effect on the performed analyses.

AbstractAims and ObjectivesTo determine the level of convergent validity of the ‘6‐Clicks’ Basic Mobility and Daily Activity with the Bedside Mobility Assessment Tool (BMAT) in patients admitted to a tertiary care academic hospital.BackgroundAccurately measuring a patient's ability to mobilise during hospitalisation is necessary but can be challenging. Two instruments, the Activity Measure for Post‐Acute Care short‐form ‘6‐Clicks’ and the BMAT, are commonly used to determine patients’ mobility levels; however, these instruments have not been psychometrically evaluated together. Understanding the characteristics between these tools can support the process of shared decision making amongst healthcare providers.DesignRetrospective Cohort adhering to the STROBE statement.MethodsUsing 13,498 individual patient admissions from an electronic health record, the BMAT score measured closest in time to the ‘6‐Clicks’ Basic Mobility and Daily Activity evaluation was collected. Spearman rank correlations with 95% confidence intervals (CIs) were calculated to determine the level of convergent validity between the ‘6‐Clicks’ Basic Mobility and Daily Activity with the BMAT. Pairwise correlations were also calculated and stratified by admitting medical service.ResultsAll correlations for the ‘6‐Clicks’ Basic Mobility or Daily Activity summative scores and the BMAT mobility levels were statistically significant and moderately correlated. The weakest correlations were seen within the Orthopaedic admitting service group. Most correlations stratified by admitting service [CVD/Pulmonary, Medicine/Hospitalist, Other Surgery and Solid Organ Transplant] were moderate. The strongest correlations were seen within the Neuro/Stroke admitting service.ConclusionModerate levels of convergent validity exist between the ‘6‐Clicks’ and the BMAT in this sample. These findings demonstrate that the construct of patient mobility is not being assessed similarly between the two instruments.Relevance to Clinical PracticeThese findings suggest the continued use of both instruments to allow interdisciplinary assessment of patient mobility status during a hospital stay.