Race-Based Care and Beliefs Regarding the Etiology of Racial Differences in Health Outcomes.

INTRODUCTION: Physicians' perspectives regarding the etiology of racial health differences may be associated with their use of race in clinical practice (race-based practice). This study evaluates whether attributing racial differences in health to genetics, culture, or social conditions is associated with race-based practice. METHODS: This is a cross-sectional analysis, conducted in 2022, of the Council of Academic Family Medicine Education Research Alliance 2021 general membership survey. Only actively practicing U.S. physicians were included. The survey included demographic questions; the Racial Attributes in Clinical Evaluation (RACE) scale (higher scores imply greater race-based practice); and 3 questions regarding beliefs that racial differences in genetics, culture (e.g., health beliefs), or social conditions (e.g., education) explained racial differences in health. Three multivariable linear regressions were used to evaluate the relationship between RACE scores and beliefs regarding the etiology of racial differences in health. RESULTS: Of the 4,314 survey recipients, 949 (22%) responded, of whom 689 were actively practicing U.S. physicians. In multivariable regressions controlling for age, gender, race, ethnicity, and practice characteristics, a higher RACE score was associated with a greater belief that differences in genetics (ß=3.57; 95% CI=3.19, 3.95) and culture (ß=1.57; 95% CI=0.99, 2.16)-in but not social conditions-explained differences in health. CONCLUSIONS: Physicians who believed that genetic or cultural differences between racial groups explained racial differences in health outcomes were more likely to use race in clinical care. Further research is needed to determine how race is differentially applied in clinical care on the basis of the belief in its genetic or cultural significance.

Insights into the skin microbiome of sickle cell disease leg ulcers.

Leg ulcers are estimated to occur in 1%-10% of North American patients with sickle cell disease (SCD). Their pathophysiology remains poorly defined, but as with other chronic wounds, it is hypothesised that the microbial milieu, or microbiome, contributes to their healing and clinical outcomes. This study utilises 16S ribosomal RNA (rRNA) gene sequencing to describe, for the first time, the microbiome of the SCD leg ulcer and its association with clinical factors. In a cross-sectional analysis of 42 ulcers, we recovered microbial profiles similar to other chronic wounds in the predominance of anaerobic bacteria and opportunistic pathogens including Staphylococcus, Corynebacterium, and Finegoldia. Ulcers separated into two clusters: one defined by predominance of Staphylococcus and smaller surface area, and the other displaying a greater diversity of taxa and larger surface area. We also find that the relative abundance of Porphyromonas is negatively associated with haemoglobin levels, a key clinical severity indicator for SCD, and that Finegoldia relative abundance is negatively associated with CD19+ B cell count. Finally, ratios of Corynebacterium:Lactobacillus and Staphylococcus:Lactobacillus are elevated in the intact skin of individuals with a history of SCD leg ulcers, while the ratio of Lactobacillus:Bacillus is elevated in that of individuals without a history of ulcers. Investigations of the skin microbiome in relation to SCD ulcer pathophysiology can inform clinical guidelines for this poorly understood chronic wound, as well as enhance broader understanding about the role of the skin microbiome in delayed wound healing.

The Meaning of Informed Consent: Genome Editing Clinical Trials for Sickle Cell Disease.

BACKGROUND: A first therapeutic target of somatic genome editing (SGE) is sickle cell disease (SCD), the most commonly inherited blood disorders, affecting more than 100,000 individuals in the United States. Advancement of SGE is contingent on patient participation in first in human clinical trials. However, seriously ill patients may be vulnerable to overestimating the benefits of early phase studies while underestimating the risks. Therefore, ensuring potential clinical trial participants are fully informed prior to participating in a SGE clinical trial is critical. Methods: We conducted a mixed-methods study of adults with SCD as well as parents and physicians of individuals with SCD. Participants were asked to complete a genetic literacy survey, watch an educational video about genome editing, complete a two-part survey, and take part in focus group discussions. Focus groups addressed topics on clinical trials, ethics of gene editing, and what is not understood regarding gene editing. All focus groups were audio-recorded, transcribed, and analyzed using conventional content analysis techniques to identify major themes. Results: Our study examined the views of SCD stakeholders regarding what they want and need to know about genome editing to make an informed decision to participate in a SGE clinical trial. Prominent themes included stakeholders' desire to understand treatment side effects, mechanism of action of SGE, trial qualification criteria, and the impact of SGE on quality of life. In addition, some physicians expressed concerns about the extent to which their patients would understand concepts related to SGE; however, individuals with SCD demonstrated higher levels of genetic literacy than estimated by physicians. Conclusions: Designing ethically robust genome editing clinical trials for the SCD population will require, at a minimum, addressing the expressed information needs of the community through culturally sensitive engagement, so that they can make informed decisions to consider participation in clinical trials.

Brain Metastases From Gynecologic Malignancies: Prevalence and Management.

OBJECTIVE: The objective of this study was to investigate the prevalence, clinicopathologic characteristics, management, and outcomes of patients with brain metastasis (BM) from gynecologic malignancies in a large hospital-based database. MATERIALS AND METHODS: The National Cancer Database (NCDB) was accessed and patients with ovarian, uterine, or cervical cancer and BM were identified. We identified those who received radiation therapy (RT) as whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Kaplan-Meier curves were generated to determine median overall survival (OS) and compared with the log-rank test. RESULTS: A total of 853 patients with BM were identified. The rate of BMs upon diagnosis was 0.4% (211/57,160) for patients with cervical cancer, 0.2% (498/243,785) for patients with uterine, and 0.2% (144/92,301) for ovarian malignancies. Only 30.4% had isolated BM, while 52.2% had lung metastasis. Approximately half of the patients (50.1%) received chemotherapy, while brain RT was administered to 324 (38%) patients. Among patients who received brain RT, only 60 (18.5%) had SRS, while 264 (81.5%) had WBRT. Patients who underwent SRS had a better survival (n=47, median OS=9 mo) than those who received WBRT (n=201, median OS=4.73 mo, P=0.018), or those who did not receive any brain RT (n=370, median OS=4.01 mo, P=0.007). CONCLUSIONS: The incidence of BM among patients with gynecologic malignancies is rare and associated with poor survival. For select patients, SRS may be associated with prolonged survival.

Perspectives of Sickle Cell Disease Stakeholders on Heritable Genome Editing.

Advances in CRISPR technology and the announcement of the first gene-edited babies have sparked a global dialogue about the future of heritable genome editing (HGE). There has been an international call for public input to inform a substantive debate about benefits and risks of HGE. This study investigates the views of the sickle cell disease (SCD) community. We utilized a mixed-methods approach to examine SCD stakeholders' views in the United States. We found SCD stakeholders hold a nuanced view of HGE. Assuming the technology is shown to be safe and effective, they are just as supportive of HGE as genetics professionals, but more supportive than the general public. However, they are also concerned about the potential implications of HGE, despite this support. As discourse surrounding HGE advances, it is crucial to engage disease communities and other key stakeholders whose lives could be altered by these interventions.

A CRISPR focus on attitudes and beliefs toward somatic genome editing from stakeholders within the sickle cell disease community.

PURPOSE: Genome editing holds both tremendous therapeutic promise and significant potential risk. Sickle cell disease (SCD), the most commonly inherited blood disorder, is a frontline candidate for the clinical applications of this tool. However, there is limited knowledge of patient community values and concerns regarding this new technology. This study aims to investigate the perspectives of three key decision-makers (patients, parents, and physicians) toward participation in future CRISPR-mediated somatic genome editing clinical trials. METHODS: We utilized a mixed-methods approach, involving an educational video tool, two-part survey, and 15 moderated, audio-recorded focus groups, which were conducted in seven U.S. cities. RESULTS: Study participants expressed hope that genome editing technology would rechart the course for SCD, but concerns related to involvement burden, uncertainty of clinical outcomes, and equity in access were identified. Major themes emerged from the focus groups: facilitators of, and barriers to, participation in future somatic genome editing clinical trials; information pertinent to the decision-making process; persons from whom participants would seek counsel before making a decision; and recommendations for the research community on meaningful engagement as clinical trials are designed and approved. CONCLUSION: The advent of genome editing has renewed hope for the SCD community, but caution tempers this optimism.