Examining resilience of individuals living with sickle cell disease in the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has impacted the physical and mental health of people worldwide including those living with genetic conditions. Sickle cell disease (SCD) is a hematologic chronic disease that causes multisystem damage and morbidity. Individuals living with SCD have had to continue managing their care for their chronic disease while following public health measures to protect against infection with COVID-19. Promoting resilience has been posited as being psychologically protective for those living with SCD. This study examines changes in resilience over time in a SCD population in the context of the COVID-19 pandemic. METHODS: Ninety-seven adults living with SCD completed two parent studies: (1) The INSIGHTS Study, a cross-sectional natural history study conducted from 2014-2019 and (2) The Living with SCD in COVID-19 Pandemic Study, an online survey conducted in 2020. Changes over time in resilience, perceived stress, emotional distress, and physical and mental health were analyzed in multivariable repeated measures model. RESULTS: Results showed that the psychological resilience of our study cohort had significantly decreased (0.19, p=0.01) over time. Resilience during the pandemic was associated with better mental health and physical health and lower perceived stress and emotional distress. In addition, results showed that marital status, education level, and employment were significantly associated with the psychological resilience of study participants. CONCLUSION: Resilience declined during the COVID-19 pandemic but was still associated with better physical and mental health outcomes. Future studies should investigate the relationship between resilience and sociodemographic factors.

Navigating Access to Cancer Care: Identifying Barriers to Precision Cancer Medicine.

OBJECTIVE: Precision medicine is revolutionizing cancer treatment. However, there has been limited investigation of barriers patients endure to access precision cancer medicine. This study aims to report the experiences of underserved patient populations with limited access to genomic testing, clinical trials, and precision cancer treatment. METHODS: A mixed-method study was employed to quantitatively evaluate patients (N=300) seeking precision cancer medicine between January 2014- August 2017. Qualitatively, we conducted semi-structured interviews with eight case managers who navigate the health care and health insurance systems to provide patients with access to precision cancer medicine care. All interviews were analyzed to identify themes. RESULTS: Within our patient cohort, 69% were diagnosed in stage I of cancer disease. Overall, 27 patients (9%) were denied treatment as a final outcome of their case due to insurance denials, 35 patients (12%) died before gaining access to precision cancer medicine, and 6 patients (2%) received precision cancer medicine through clinical trials. Four broad thematic areas emerged from the qualitative analysis: 1) lack of patient, provider and insurer knowledge of precision cancer medicine; 2) barriers to clinical trial participation; 3) lack of patient health literacy; and 4) barriers to timely access to care. CONCLUSION: Our combined analyses suggest that both system-level and patient-level barriers limit patient access to precision cancer medicine options. Additionally, we found that these barriers may exist not only for traditionally underserved patients, but also for resourced and insured patients trying to access precision cancer medicine.

Splenic infarction in sickle cell trait: A comprehensive systematic review of case studies.

Sickle cell trait (SCT), a commonly asymptomatic condition, has many associated clinical complications that upon presentation, can be very difficult to attribute to SCT. The effects of SCT on the spleen, for example, are not completely understood, though there have been a number of case reports detailing related complications in diverse populations. Our objective was to perform the first comprehensive case report review of splenic infarction in SCT patients to highlight the relevance of this seemingly rare condition. We conducted an extensive literature search reviewing case reports and case series of acute splenic infarctions from 1970 to 2020. This comprehensive search resulted in 54 articles with a total of 85 individuals. The ages ranged from 7 to 65, 12% were female. Individuals were of African-American (26%), European (16%), South Asian (13%), Middle Eastern (7%), Latin American (7%), North or East African (4%), Mediterranean (4%), West African (1%), and unknown (22%) origins. Although splenic infarct in SCT patients has been associated with high altitudes, 39% of cases reporting altitude occurred below 3000 m. Among cases where HbS values were recorded, 88% occurred in individuals with HbS levels higher than 35%, suggesting that high HbS values may be a risk factor for splenic infarction. Our findings indicate that splenic infarct occurs across a wide range of demographic populations and environmental settings. While our understanding of SCT evolves, the findings here suggest that future advances in research and healthcare could benefit more from real-time surveillance and registry initiation for various SCT outcomes such as splenic infarct.

Lower hair cortisol among patients with sickle cell disease may indicate decreased adrenal reserves.

INTRODUCTION: Sickle cell disease (SCD) is a chronic illness that presents with a wide range of phenotypic variation. Stress may be a contributing factor to differences that are found in this population. OBJECTIVES: Our objective is to determine the relationship between hair cortisol content (HCC), a biomarker of stress, and other clinical measures in individuals with SCD. METHODS: We collected hair samples and other clinical measures from 73 subjects with SCD (mean age: 39 ± 12 years, 63% female). RESULTS: HCC was lower among individuals who had greater than 30% hemoglobin S, compared with those who had less than 30% hemoglobin S (W=272.5, P=0.01). Lower HCC was also associated with report of not being on a chronic transfusion program (ß=48.34, SE=14.09, P=0.001) and higher ferritin levels (ß=-0.006, SE=0.002, P=0.02). Furthermore, HCC was significantly correlated with serum cortisol (rs=0.26, P=0.03) and corticosterone (rs=0.29, P=0.01). We also observed a consistent pattern of low steroid values among our population. CONCLUSION: Our findings suggest that individuals with higher hemoglobin S and ferritin, both markers of severe SCD, may have decreased cortisol levels. This is consistent with the relationship we observed between higher HCC among individuals who are on a chronic blood transfusion program, which typically increases quality of life. Our results suggest that hair cortisol may be an indicator in patients with SCD who could be at risk for developing adrenal insufficiency. We recommend that clinicians treating patients with SCD follow the Endocrine Society guidelines for testing for adrenal insufficiency and treat accordingly.

Cultivating diversity as an ethos with an anti-racism approach in the scientific enterprise.

The diversity of the U.S. population is currently not reflected in the genomic workforce and across the greater scientific enterprise. Although diversity and inclusion efforts have focused on increasing the number of individuals from underrepresented groups across scientific fields, structural racism remains. Thus, the cultivation and adoption of diversity as an ethos requires shifting our focus to being intentional about an institution's character, culture, and climate. One way for this ethos to be sustained is by facilitating an intentional anti-racism approach within the field. Adopting a new perspective on diversity utilizing an anti-racism approach will support genomics researchers as we build supportive, collaborative research environments. We seek to expand critical thought in the framing of diversity in the research enterprise and propose an anti-racism approach that informs deliberate actions required to address structural racism.

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.

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 Comparison of Physicians' and Nurse Practitioners' Use of Race in Clinical Decision-Making.

Objective: The debate over use of race as a proxy for genetic risk of disease continues, but little is known about how primary care providers (nurse practitioners and general internal medicine physicians) currently use race in their clinical practice. Our study investigates primary care providers' use of race in clinical practice. Methods: Survey data from three cross-sectional parent studies were used. A total of 178 nurse practitioners (NPs) and 759 general internal medicine physicians were included. The outcome of interest was the Racial Attributes in Clinical Evaluation (RACE) scale, which measures explicit use of race in clinical decision-making. Predictor variables included the Genetic Variation Knowledge Assessment Index (GKAI), which measures the providers' knowledge of human genetic variation. Results: In the final multivariable model, NPs had an average RACE score that was 1.60 points higher than the physicians' score (P=.03). The GKAI score was not significantly associated with the RACE outcome in the final model (P=.67). Conclusions: Physicians had more knowledge of genetic variation and used patients' race less in the clinical decision-making process than NPs. We speculate that these differences may be related to differences in discipline-specific clinical training and approaches to clinical care. Further exploration of these differences is needed, including examination of physicians' and NPs' beliefs about race, how they use race in disease screening and treatment, and if the use of race is contributing to health care disparities.

Primary Care Physicians' Collection, Comfort, and Use of Race and Ethnicity in Clinical Practice in the United States.

PURPOSE: The clinical utility of race and ethnicity has been debated. It is important to understand if and how race and ethnicity are communicated and collected in clinical settings. We investigated physicians' self-reported methods of collecting a patient's race and ethnicity in the clinical encounter, their comfort with collecting race and ethnicity, and associations with use of race in clinical decision-making. METHODS: A national cross-sectional study of 787 clinically active general internists in the United States. Physicians' self-reported comfort with collecting patient race and ethnicity, their collection practices, and use of race in clinical care were assessed. Bivariate and multivariable regression analyses were conducted to examine associations between comfort, collection practices, and use of race. RESULTS: Most physicians asked patients to self-report their race or ethnicity (26.5%) on an intake form or collected this information directly from patients (26.2%). Most physicians were comfortable collecting patient race and ethnicity (84.3%). Physicians who were more comfortable collecting patient race and ethnicity (ß= 1.65; [95% confidence interval; CI 0.03-3.28]) or who directly collected patients' race and ethnicity (ß= 1.24 [95% CI 0.07-2.41]) were more likely to use race in clinical decision-making than physicians who were uncomfortable. CONCLUSIONS: This study documents variation in physician comfort level and practice patterns regarding patient race and ethnicity data collection. As the U.S. population becomes more diverse, future work should examine how physicians speak about race and ethnicity with patients and their use of race and ethnicity data impact patient-physician relationships, clinical decision-making, and patient outcomes.

The psychosocial impact of leg ulcers in patients with sickle cell disease: I don't want them to know my little secret.

BACKGROUND: Sickle cell disease (SCD) impacts millions of individuals worldwide and more than 100,000 people in the United States. Leg ulcers are the most common cutaneous manifestation of SCD. The health status of individuals living with chronic leg ulcers is not only influenced by clinical manifestations such as pain duration and intensity, but also by psychosocial factors. Garnering insights into the psychosocial impact can provide a more holistic view of their influence on quality of life. METHODS: Semi-structured interviews were conducted with participants living with active SCD-associated leg ulcers or with a history of ulcers. Subjects were recruited from an ongoing study (INSIGHTS, Clin Trial.Gov NCT02156102) and consented to this qualitative phase of the study. Five areas were explored: leg ulcer pain, physical function, social-isolation, social relationships and religious support. Data was collected from 20 individuals during these interviews and a thematic analysis was performed and reported. RESULTS: Twenty participants with a mean age of 42.4 (SD ± 11.1years) were included in the study. Major themes identified included:1) pain (acute and chronic); 2) compromised physical function as demonstrated by decreased ability to walk, run, and play sports; 3) social isolation from activities either by others or self-induced as a means of avoiding certain emotions, such as embarrassment; 4) social relationships (family support and social network); 5) support and comfort through their religion or spirituality. CONCLUSIONS: SCD patients with leg ulcers expressed that they experience social isolation, intense and frequent ulcer pain, and difficulty in physical function. SCD-associated leg ulcers have been studied from a clinical approach, but the psychosocial factors investigated in this study informs how quality of life is impacted by the leg ulcers.

Nurses' Use of Race in Clinical Decision Making.

PURPOSE: To examine nurses' self-reported use of race in clinical evaluation. DESIGN: This cross-sectional study analyzed data collected from three separate studies using the Genetics and Genomics in Nursing Practice Survey, which includes items about use of race and genomic information in nursing practice. The Racial Attributes in Clinical Evaluation (RACE) scale was used to measure explicit clinical use of race among nurses from across the United States. METHODS: Multivariate regression analysis was used to examine associations between RACE score and individual-level characteristics and beliefs in 5,733 registered nurses. FINDINGS: Analysis revealed significant relationships between RACE score and nurses' race and ethnicity, educational level, and views on the clinical importance of patient demographic characteristics. Asian nurses reported RACE scores 1.41 points higher than White nurses (p < .001), and Black nurses reported RACE scores 0.55 points higher than White nurses (p < .05). Compared to diploma-level nurses, the baccalaureate-level nurses reported 0.69 points higher RACE scores (p < .05), master's-level nurses reported 1.63 points higher RACE scores (p < .001), and doctorate-level nurses reported 1.77 points higher RACE scores (p < .01). In terms of clinical importance of patient characteristics, patient race and ethnicity corresponded to a 0.54-point increase in RACE score (p < .001), patient genes to a 0.21-point increase in RACE score (p < .001), patient family history to a 0.15-point increase in RACE score (p < .01), and patient age to a 0.19-point increase in RACE score (p < .001). CONCLUSIONS: Higher reported use of race among minority nurses may be due, in part, to differential levels of racial self-awareness. A relatively linear positive relationship between level of nursing degree nursing education and use of race suggests that a stronger foundation of knowledge about genetic ancestry, population genetics and the concept "race" and genetic ancestry may increase in clinical decision making could allow nurses to more appropriately use of race in clinical care. Integrating patient demographic characteristics into clinical decisions is an important component of nursing practice. CLINICAL RELEVANCE: Registered nurses provide care for diverse racial and ethnic patient populations and stand on the front line of clinical care, making them essential for reducing racial and ethnic disparities in healthcare delivery. Exploring registered nurses' individual-level characteristics and clinical use of race may provide a more comprehensive understanding of specific training needs and inform nursing education and practice.