Bidirectional Relationship Between Sickle Cell Disease and Food Insecurity: Scoping Review.

Introduction: In the United States, sickle cell disease (SCD)-the homozygous inheritance of a point mutation within the beta-globin chain of hemoglobin-affects between 80,000 and 100,000 people. Adequate nutrition can influence the pathophysiology of SCD, and individuals with SCD who are undernourished are more likely to have impaired immune function and disease exacerbation. Undernourishment is often caused by food insecurity (FI), which is defined as "a household-level economic and social condition of limited or uncertain access to adequate food" by the USDA. FI disproportionately affects African Americans, a population disproportionately affected by SCD in the United States. Objectives: We performed a scoping review to better understand the relationship between FI and SCD severity. Methods: A comprehensive search for peer-reviewed research articles and meeting abstracts was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selected studies were reviewed for descriptive analysis by three independent reviewers. Results: In total, 72 studies were identified, 62 were excluded for meeting inclusion criteria. The remaining 10 studies, 5 of which were meeting abstracts, were reviewed. Although limited evidence is available, the results of this scoping review suggest a bidirectional relationship between SCD and FI. Seven key themes were identified to help elucidate this relationship: 1) prevalence of FI among individuals with SCD, 2) child versus caregiver experiences of FI, 3) psychosocial factors, 4) food assistance benefits, 5) dietary intake, 6) external spending, 7) healthcare utilization. Conclusion: Findings from this scoping review suggest how SCD and FI work in tandem to exacerbate each other. Furthermore, the findings illustrate current gaps in the literature and opportunities for actions to address FI among individuals living with SCD.

"Resilience?" perspectives from adults living with sickle cell disease.

OBJECTIVES: This study examines and explores the definition of resilience in adults living with sickle cell disease (SCD) in the United States (U.S.). METHODS: Participants were recruited between 2014 and 2018, from across the U.S. as part of Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study (INSIGHTS). Inclusion criteria included age of 18+, a diagnosis of SCD, and completion of the Brief Resilience Scale (BRS). Thirty participants were randomly selected, 15 each from the lowest and highest BRS quartile. A semi-structured qualitative interview was administered. All participants identified as Black with an average age of 42.5 (13 F, 17 M). RESULTS: Three main concepts emerged in response to the question "How do you define resilience?" (a) not giving up (b) how one deals with challenges and (c) moving forward. CONCLUSION: This study suggests that current definitions of resilience used in validated survey measures do not match how adults living with SCD define resilience. Our results expand the understanding of resilience as a dynamic process, more about the process of "not giving up." These findings suggest that providers may find it productive to facilitate conversations with adults living with SCD around "how" they approach challenges. This study is also the first of its kind to examine resilience in a community living with SCD.

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.

Patient Perceptions on the Advancement of Noninvasive Prenatal Testing for Sickle Cell Disease among Black Women in the United States.

BACKGROUND: Noninvasive prenatal testing (NIPT) designed to screen for fetal genetic conditions, is increasingly being implemented as a part of routine prenatal care screening in the United States (US). However, these advances in reproductive genetic technology necessitate empirical research on the ethical and social implications of NIPT among populations underrepresented in genetic research, particularly Black women with sickle cell disease (SCD). METHODS: Forty (N = 40) semi-structured interviews were conducted virtually with Black women in the US (19 participants with SCD; 21 participants without SCD) from June 2021 to January 2022. We employed a qualitative approach to examine the study participants' perceptions of the potential advancement of NIPT for screening SCD in the fetus. Data were analyzed using NVivo 12 qualitative software. RESULTS: The themes revealed the complexities involving the intersectional lived experiences of SCD, prenatal care, lack of synergy among health providers, and NIPT decision-making. The results further revealed that even when Black women have shared commonalities in their lived experiences while navigating SCD and motherhood, their perceptions of NIPT screening technologies are divergent. CONCLUSION: Expanding the ethical discourse on the social implications of NIPT is critical to fully elucidate how Black women perceive NIPT's utility, particularly as NIPT advances to screen for SCD in the fetus. Neglecting to include Black women with genetic conditions in empirical studies on NIPT may contribute to ongoing health inequities and limit and constrain reproductive choices among Black women with and without SCD.

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.

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.

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.

Is there a way to reduce the inequity in variant interpretation on the basis of ancestry?

The underrepresentation of non-European ancestry groups in current genomic databases complicates interpretation of their genetic test results, yielding a much higher prevalence of variants of uncertain significance (VUSs). Such VUS findings can frustrate the goals of genetic testing, create anxiety in patients, and lead to unnecessary medical interventions. Approaches to addressing underrepresentation of people with genetic ancestries other than European are being undertaken by broad-based recruitment efforts. However, some underrepresented groups have concerns that might preclude participation in such efforts. We describe here two initiatives aimed at meeting the needs of underrepresented ancestry groups in genomic datasets. The two communities, the Sephardi Jewish community in New York and First Peoples of Canada, have very different concerns about contributing to genomic research and datasets. Sephardi concerns focus on the possible negative effects of genetic findings on the marriage prospects of family members. Canadian Indigenous populations seek control over the research uses to which their genetic data would be put. Both cases involve targeted efforts to respond to the groups' concerns; these efforts include governance models aimed at ensuring that the data are used primarily to inform clinical test analyses and at achieving successful engagement and participation of community members. We suggest that these initiatives could provide models for other ancestral groups seeking to improve the accuracy and utility of clinical genetic testing while respecting the underlying preferences and values of community members with regard to the use of their genetic data.

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.

Evolving use of ancestry, ethnicity, and race in genetics research-A survey spanning seven decades.

To inform continuous and rigorous reflection about the description of human populations in genomics research, this study investigates the historical and contemporary use of the terms "ancestry," "ethnicity," "race," and other population labels in The American Journal of Human Genetics from 1949 to 2018. We characterize these terms' frequency of use and assess their odds of co-occurrence with a set of social and genetic topical terms. Throughout The Journal's 70-year history, "ancestry" and "ethnicity" have increased in use, appearing in 33% and 26% of articles in 2009-2018, while the use of "race" has decreased, occurring in 4% of articles in 2009-2018. Although its overall use has declined, the odds of "race" appearing in the presence of "ethnicity" has increased relative to the odds of occurring in its absence. Forms of population descriptors "Caucasian" and "Negro" have largely disappeared from The Journal (<1% of articles in 2009-2018). Conversely, the continental labels "African," "Asian," and "European" have increased in use and appear in 18%, 14%, and 42% of articles from 2009-2018, respectively. Decreasing uses of the terms "race," "Caucasian," and "Negro" are indicative of a transition away from the field's history of explicitly biological race science; at the same time, the increasing use of "ancestry," "ethnicity," and continental labels should serve to motivate ongoing reflection as the terminology used to describe genetic variation continues to evolve.

Ethical Issues in Genetics and Infectious Diseases Research: An Interdisciplinary Expert Review.

PURPOSE: Research in genetics and infectious diseases (ID) presents novel configurations of ethical, legal, and social issues (ELSIs) related to the intersection of genetics with public health regulations and the control of transmissible diseases. Such research includes work both in pathogen genetics and on the ways that human genetics affect responses to ID. This paper identifies and systematizes the unique issues at this intersection, based on an interdisciplinary expert review. BASIC PROCEDURES: This paper presents results of a formal issue-spotting exercise among twenty experts in public health, law and genomics, biobanking, genetic epidemiology, ID medicine and public health, philosophy, ethics and ID, ethics and genomics, and law and ID. The focus of the exercise was on the collection, storage, and sharing of genetic information relating to ID. MAIN FINDINGS: The issue-spotting exercise highlighted the following ELSIs: risks in reporting to government authorities, return of individual research results, and resource allocation - each taking on specific configurations based on the balance between public health and individual privacy/protection. PRINCIPAL CONCLUSIONS: The public health implications of interactions between genomics and ID frame considerations for equity and justice. In the context of the COVID-19 pandemic, these issues are especially pressing.

Practices and Attitudes toward Returning Genomic Research Results to Low-Resource Research Participants.

INTRODUCTION: Many research programs are challenged to accommodate low-resource research participants' (LRRP) ancillary care needs when returning genomic research results. We define LRRP as those who are low income, uninsured, underinsured, or facing barriers to act upon the results returned. This study evaluates current policies and practices surrounding return of results (RoR) to LRRP, as well as the attitudes of investigators toward providing ancillary care to LRRP. METHODS: A semi-structured interview study was conducted with representatives of 35 genomic research programs nationwide. Eligible programs were returning, or planning to return, medically actionable genomic results to participants. RESULTS: Three content categories emerged from this study, including: (1) RoR structures, (2) barriers to RoR to LRRP, and (3) solutions to meet community and LRRP needs. Three major structures of RoR emerged: (1) RoR Embedded in Clinical Care, (2) RoR Independent of Clinical Care, and (3) Reliance on Clinical Partnerships to Facilitate RoR. Inadequacy of program resources to address the needs of LRRP was commonly considered a significant obstacle. The attitudes and views of informants regarding responsibility to provide ancillary care for LRRP receiving genomic results were highly varied. Some informants believed that genomic sequencing and testing was not a priority for LRRP because of other pressing issues in their lives, such as housing and food insecurity. Research programs differ regarding whether clinical and social support for LRRP is considered within the purview of the research team. Some programs instituted accommodations for LRRP, including social work referral and insurance enrollment assistance. CONCLUSION: Support to access downstream treatment is not readily available for LRRP in many genomic research programs. Development of best practices and policies for managing RoR to LRRP is needed.

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.

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.

Social support networks of adults with sickle cell disease.

Sickle cell disease (SCD) can cause both physical and psychological complications, such as severe pain and depression. These effects often necessitate social and caregiving support. Few studies have assessed support networks within the adult SCD population. Here, we describe the support networks of adults with SCD and identify who in these networks (1) provides emotional support, (2) is dependable during crisis situations, including social and financial adversities, and (3) provides assistance in health crises. Forty-nine adults with SCD completed surveys and social network assessments through interview. Generalized mixed-effects linear regression models were fitted to investigate the composition of support provision within these personal networks. Our findings indicate that parents and 'other important people' (e.g., friends, spouses) play key roles in the support provided to those with SCD. Siblings with SCD appeared to be more emotionally supportive than unaffected siblings. With much research centered around the pediatric and adolescent SCD populations, focus needs to extend to adults and the individuals involved in their care and disease management. Understanding the flow of support within these networks can help genetic counselors and healthcare providers to better identify both social ties that serve as support resources and less supportive relationships for individuals living with SCD and other chronic genetic conditions that might be targeted for intervention.

The genomics workforce must become more diverse: a strategic imperative.

The National Human Genome Research Institute (NHGRI) recently published a new strategic vision for the future of human genomics, the product of an extensive, multi-year engagement with numerous research, medical, educational, and public communities. The theme of this 2020 vision-The Forefront of Genomics-reflects NHGRI's critical role in providing responsible stewardship of the field of human genomics, especially as genomic methods and approaches become increasingly disseminated throughout biomedicine. Embracing that role, the new NHGRI strategic vision features a set of guiding principles and values that provide an ethical and moral framework for the field. One principle emphasizes the need to champion a diverse genomics workforce because "the promise of genomics cannot be fully achieved without attracting, developing, and retaining a diverse workforce, which includes individuals from groups that are currently underrepresented in the genomics enterprise." To build on the remarkable metamorphosis of the field over the last three decades, enhancing the diversity of the genomics workforce must be embraced as an urgent priority. Toward that end, NHGRI recently developed an "action agenda" for training, employing, and retaining a genomics workforce that reflects the diversity of the US population.

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.