Precision, integrative medicine for pain management in sickle cell disease.

Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies. In this review, we acknowledge that implementing personalized pain treatment strategies in SCD, which is a guideline-recommended strategy, is currently fraught with limitations. The full implementation of pharmacological and biobehavioral pain approaches targeting mechanistic pain pathways faces challenges due to limited knowledge and limited financial and personnel support. We recommend personalized medicine, pharmacogenomics, and integrative medicine as aspirational strategies for improving pain care in SCD. As an organizing model that is a comprehensive framework for classifying pain subphenotypes and mechanisms in SCD, and for guiding selection of specific strategies, we present evidence updating pain research pioneer Richard Melzack's neuromatrix theory of pain. We advocate for using the updated neuromatrix model to subphenotype individuals with SCD, to better select personalized multimodal treatment strategies, and to identify research gaps fruitful for exploration. We present a fairly complete list of currently used pharmacologic and non-pharmacologic SCD pain therapies, classified by their mechanism of action and by their hypothesized targets in the updated neuromatrix model.

Psychometrics of the Sickle Cell Disease Health-Related Stigma Scale-Short Form.

Health-related stigma, a form of devaluation related to a health condition, is common in individuals with sickle cell disease (SCD). Pain is the hallmark symptom of SCD, and health-related stigma is often described during care-seeking for pain management. Few published instruments measure health-related stigma in individuals with SCD. This study builds on the psychometrics of the 30- and 40-item Sickle Cell Disease Health-Related Stigma Scale (SCD-HRSS). In a sample of 197 adults with SCD, the results support the reliability and validity of a 21-item scale, the SCD-HRSS-Short Form, with an overall Cronbach's alpha reliability of 0.91 and discriminant validity with the PROMIS-29 subscales (anxiety, depressive symptoms, pain interference, physical fatigue, sleep, and role satisfaction). A shorter yet reliable and valid scale may decrease the burden for this underrepresented, minoritized population while still providing important information regarding their experiences of stigmatization.

"It Is Not Easy": Cultural Influences of Sickle Cell Disease Management in Rural, Eastern Sierra Leone.

Sickle cell disease (SCD) is a chronic genetic disease that causes life-threatening complications and requires robust comprehensive management. Developing comprehensive SCD programs in sub-Saharan African countries requires knowledge of the cultural factors affecting health-seeking behavior. We utilized an ethnographic approach and the frameworks of Dutta and Habermas to explore cultural factors influencing SCD management in rural Sierra Leone. A purposive sample of 27 individuals with SCD and their family and professional caregivers were observed and interviewed from March 2019 to April 2019. We identified four domains (Cultural Beliefs, Cultural Values, Cultural Practices, and Dealing with SCD) of cultural influences on SCD management, and 12 sub-themes (related to collectivism; spiritual, traditional, and Western beliefs and practices; and lived experiences) that reflect the personal, social, structural, and contextual complexities of SCD management. Further research regarding roles of traditional and spiritual leaders, combinations of Western and traditional practices, and culturally centered interventions is warranted.

Progressing Preemptive Genotyping of CYP2C19 Allelic Variants for Sickle Cell Disease Patients.

AIMS: Interindividual variability in drug response and adverse effects have been described for proton pump inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, tricyclic antidepressants, and anti-infectives, but little is known about the safety and efficacy of these medications in patients with sickle cell disease (SCD). We genotyped the CYP2C19 gene which has been implicated in the metabolism of these drugs in an SCD patient cohort to determine the frequencies of reduced function, increased function, or complete loss-of-function variants. MATERIALS AND METHODS: DNAs from 165 unrelated SCD patients were genotyped for nine CYP2C19 (*2, *3, *4, *5, *6, *7,*8, *12, and *17) alleles using the iPLEX® ADME PGx multiplex panel. RESULTS: Three CYP2C19 alleles (*2, *12, and *17) were detected with the following frequencies: 0.209, 0.006, and 0.236, respectively. The predicted phenotype frequencies were distributed as extensive (31.5%), intermediate (24.8%), poor (5.5%), ultrarapid (30.3%), and unknown metabolizers (7.9%). DISCUSSION: Prognostic genotyping is potentially useful for identifying SCD patients with allelic variants linked to proven clinical pharmacokinetic consequences for several drugs metabolized by the CYP2C19 gene. However, the main challenge to implementing a genetics-guided prescribing practice is ensuring concordance between CYP2C19 genotypes and metabolic phenotypes in SCD patients.

Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management.

Interindividual variability in analgesic effects of nonsteroidal anti-inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in the CYP2C8 and CYP2C9 enzymes. We described CYP2C8 and CYP2C9 genotype/phenotype profiles and frequency of emergency department (ED) visits for pain management in an African American SCD patient cohort. DNA from 165 unrelated patients was genotyped for seven CYP2C8 and 15 CYP2C9 alleles using the iPLEX ADME PGx multiplexed panel. CYP2C8*1 (0.806),*2 (0.164), *3 (0.018), and *4 (0.012) alleles were identified. Genotype frequencies were distributed as homozygous wild type (66.7%), heterozygous (27.8%), and homozygous variant/compound heterozygous (5.4%), respectively. CYP2C9*1 (0.824), *2 (0.027), *3 (0.012), *5 (0.009), *6 (0.009), *8 (0.042), *9 (0.061), and *11(0.015) were observed with extensive (68.5%), intermediate (18.1%) and poor predicted metabolizers (0.6%), respectively. Fifty-two and 55 subjects, respectively had at least one variant CYP2C8 or CYP2C9 allele. Although the distribution of the CYP2C9 (p = 0.0515) phenotypes was marginally significantly in high and low ED users; some CYP2C8 and CYP2C9 allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure. CYP2C8 and CYP2C9 preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.

CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease cohort: implications for NSAIDs pharmacotherapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain in patients with sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We determined the frequencies of CYP2C9 alleles in an African American pediatric SCD cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7 and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11, and *13) was performed using restriction fragment length polymorphism-PCR assays and the Tag-It™ Mutation Detection System. The wild type *1 allele frequency was 0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of the study cohort were predicted extensive metabolizers (*1/*1) and 30% were intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9 using an expanded assay panel facilitated improved classification of predicted drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated and underscores the need for studies on substrate-specific effects of variant alleles common in populations with genetic susceptibility to SCD.

Advancing genomic research and reducing health disparities: what can nurse scholars do?

PURPOSE: Advances in genomic research are improving our understanding of human diseases and evoking promise of an era of genomic medicine. It is unclear whether genomic medicine may exacerbate or attenuate extant racial group health disparities. We delineate how nurse scholars could engage in the configuration of an equitable genomic medicine paradigm. ORGANIZING CONSTRUCT: We identify as legitimate subjects for nursing scholarship the scientific relevance, ethical, and public policy implications for employing racial categories in genomic research in the context of reducing extant health disparities. FINDINGS: Since genomic research is largely population specific, current classification of genomic data will center on racial and ethnic groups. Nurse scholars should be involved in clarifying how putative racial group differences should be elucidated in light of the current orthodoxy that genomic solutions may alleviate racial health disparities. CONCLUSIONS: Nurse scholars are capable of employing their expertise in concept analysis to elucidate how race is used as a variable in scientific research, and to use knowledge brokering to delineate how race variables that imply human ancestry could be utilized in genomic research pragmatically in the context of health disparities. CLINICAL RELEVANCE: In an era of genomic medicine, nurse scholars should recognize and understand the challenges and complexities of genomics and race and their relevance to health care and health disparities.

Usability evaluation of the interactive Personal Patient Profile-Prostate decision support system with African American men.

BACKGROUND: The Personal Patient Profile-Prostate (P4) program is an interactive Web-based decision support system that provides men with localized prostate cancer customized education and coaching with which to make the best personal treatment decision. This study assessed functionality and usability of the P4 program and identified problems in user-computer interaction in a sample of African American men. METHODS: Usability testing was conducted with 12 community-dwelling African American adult men. The health status of participants was not known or collected by the research team. Each participant worked with the P4 program and provided simultaneous feedback using the "think aloud" technique. Handwritten field notes were collated and assigned to 3 standard coded categories. Aspects of P4 program usability was made based on common issues in the assigned categories. Summary statistics were derived for types and frequency of usability issues noted in the coded data. RESULTS: Twelve participants reported a total of 122 usability comments, with a mean of 9 usability comments. The most common usability issue by participant was completeness of information content, which comprised 53 (43%) of the total issues. Comprehensibility of text and graphics was second, comprising 51 (42%) of the total issues. CONCLUSION: This study provided initial inventory of usability issues for community African American men that may potentially interfere with application of the P4 system in the community setting and overall system usability, confirming the need for usability testing of a culturally appropriate Internet-based decision support system before community application.

Cytochrome p450 enzyme polymorphism frequency in indigenous and native american populations: a systematic review.

OBJECTIVE: The purpose of our study was to evaluate the evidence on the prevalence of cytochrome P450 enzyme polymorphisms as potential genetic factors influencing drug efficacy and safety in the indigenous populations of the American hemispheres. METHODS: We conducted a systematic review of studies published between 1985 and 2006 using the Pubmed database. RESULTS: We identified only 10 original research studies on CYP2A6, CYP2D6, CYP2C9, CYP2C19 and CYP2E1 in 13 indigenous American populations. Interethnic differences in the frequency of CYP450 genetic variants existed both among the examined indigenous populations and in comparison with African, Asian and European populations. CONCLUSIONS: There are surprisingly few data on CYP450 enzyme polymorphisms in indigenous American populations, and it is difficult to draw any clear inferences about how these populations might be expected to respond to drugs in relation to other racial or ethnic groups. This lack of information could create a barrier to the use of pharmacogenetic testing in these populations. Collaborative partnerships between indigenous communities and researchers are needed to avail the clinical benefits of CYP450 enzyme polymorphism testing to indigenous populations.