Views of adults living with sickle cell disease on the theoretical return of secondary genomic findings.

PURPOSE: Although the body of research investigating research participants' opinions on the return of actionable secondary genomic findings grows, there has been limited study of individuals with genetic conditions, such as sickle cell disease (SCD). It is imperative that the views of diverse research participants on return of results (RoR) be investigated and rooted in the context of advancing health equity in genomics research. METHODS: We conducted qualitative, semi-structured interviews with 30 adults living with SCD with differing insurance coverages and utilized a directed content analysis to derive themes. RESULTS: Study findings show that living with SCD is a key influence on views of RoR. Participants were in favor of RoR while expressing concern regarding the burden RoR would place on their SCD management. Respondents also expressed an expectation for researchers to devote resources toward seeking ancillary care downstream and discussed how barriers faced when navigating SCD would inform their access to ancillary care. CONCLUSION: Research participants living with chronic genetic conditions such as SCD are generally in favor of RoR but anticipate experiencing barriers to care similar to those faced navigating their SCD. Understanding the views of diverse cohorts on RoR will help researchers better understand downstream barriers participants may face.

Leg ulcers are indicators of systemic dysfunction in individuals with sickle cell disease.

Leg ulcers in individuals living with Sickle Cell Disease are evidence of systemic dysfunction. Data from a U.S. study link leg ulcers to wider pulse pressure and markers of chronic hemolysis, inflammation, renal, and liver dysfunction.

Educational considerations based on medical student use of polygenic risk information and apparent race in a simulated consultation.

PURPOSE: To craft evidence-based educational approaches related to polygenic risk score (PRS) implementation, it is crucial to forecast issues and biases that may arise when PRS are introduced in clinical care. METHODS: Medical students (N = 84) were randomized to a simulated primary care encounter with a Black or White virtual reality-based patient and received either a direct-to-consumer-style PRS report for 5 common complex conditions or control information. The virtual patient inquired about 2 health concerns and her genetic report in the encounter. Data sources included participants' verbalizations in the simulation, care plan recommendations, and self-report outcomes. RESULTS: When medical students received PRSs, they rated the patient as less healthy and requiring more strict advice. Patterns suggest that PRSs influenced specific medical recommendations related to the patient's concerns, despite student reports that participants did not use it for that purpose. We observed complex patterns regarding the effect of patient race on recommendations and behaviors. CONCLUSION: Educational approaches should consider potential unintentional influences of PRSs on decision-making and evaluate ways that they may be applied inconsistently across patients from different racial groups.

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.

An Examination of John Henryism in Adults Living with Sickle Cell Disease.

BACKGROUND: John Henryism (JH) is a behavioral predisposition for high-effort coping with adversity. JH has been associated with hypertension in Black Americans with low socioeconomic status (SES) and is also found to be associated with psychological well-being. Sickle cell disease (SCD), a rare genetic disease largely affecting Black Americans in the United States, presents as a chronic condition that may benefit from a deeper understanding of the impact of JH on overall health. PURPOSE: This study examined the association between high and low JH and diastolic blood pressure, systolic blood pressure, hypertension prevalence, and sleep function. We relied on the biopsychosocial transaction model to adjust for relevant clinical and sociodemographic variables. METHODS: This was a cross-sectional secondary analysis of 274 adults with SCD living in the United States and recruited between 2014 and 2020. Study visits consisted of physical examinations, medical history, demographic, and psychosocial questionnaires. Adjusted linear regressions estimated associations between high and low JH and diastolic and systolic blood pressure as well as self-reported sleep function. Multivariable logistic regression was used to examine associations with hypertension prevalence. RESULTS: High JH was significantly associated with lower diastolic blood pressure (ß = - 2.98; 95% confidence interval = - 5.92, - 0.04) but higher sleep dysfunction (ß = 2.76; 95% confidence interval = 1.45, 4.07). CONCLUSIONS: Overall, we found positive psychological coping resources associated with high JH, with the exception of sleep. CLINICALTRIALS: gov Identifier: NCT02156102.

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.

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.

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.

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.