BACKGROUND:Gene therapy for Haemophilia B has received FDA approval, offering patients a transformative therapeutic option. However, effective communication about the benefits, risks, long-term efficacy and follow-up of gene therapy remains essential for informed decision-making. This study aimed to explore the diverse expectations, concerns and perspectives of patients with Haemophilia B, their caregivers and healthcare professionals (HCPs) regarding gene therapy and to identify strategies for improving communication. METHODS:A prospective qualitative study was conducted using semi-structured interviews with male patients aged ≥12 years with moderate or severe Haemophilia B (factor level ≤ 2%), their caregivers and HCPs (physicians, nurses, social workers, advanced practice providers and pharmacists). Interviews were audio-recorded, transcribed and analysed thematically. RESULTS:Thirty participants were interviewed, including 15 patients (mean age, 21.1 years), caregivers and 15 HCPs across the United States. Patients and caregivers emphasised five themes: (1) current challenges; (2) hope and optimism; (3) concerns and skepticism; (4) the complex emotional challenges of decision-making and (5) preferences for transparent, patient-friendly communication. HCPs identified four complementary themes: (1) variable patient knowledge; (2) the need for transparency in discussing 'curative' language; (3) factors influencing treatment decisions (trust, prior experiences and financial concerns) and (4) strategies to improve communication (clear language, visuals and testimonials). CONCLUSION:Stakeholders view gene therapy as both promising and uncertain. Targeted educational interventions, transparent communication and patient-centred decision discussions are essential to fill knowledge gaps and support informed consent in this transformative era of treatment for Haemophilia B.

Adolescents and young adults (AYA) with sickle cell disease (SCD) experience increased acute care utilization for pain. The evolution of pain-specific patient-reported outcomes (PROs) during this period is poorly understood. To characterize AYA pain, we conducted a cross-sectional multi-institutional study of individuals with SCD (≥8 years) grouped as preadolescents (8-13.99 years), adolescents (14-17.99 years), and young adults (≥18 years). Pain-specific PROs were assessed using Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference (primary outcome). Secondary outcomes included PROMIS Pain Behavior and Pain Intensity, pain duration (>7 days) and frequency (≥3-4 days/week). Social determinants of health (SDOH) associations with Pain Interference were evaluated. Among 114 individuals, there were no differences in sex, genotype, or hemoglobin across age groups. Pain Interference (55.07 vs 47.68, p=0.0011) was worse in young adults compared to adolescents, with greater prevalence of moderate/severe Pain Interference (29.7% vs 0%, p=0.0016). The prevalence of moderate/severe Pain Behavior was 45.95% in young adults, 4% in early adolescents, and 0% in adolescents. Pain intensity was worse in young adults compared to adolescents (4.03 vs 1.7, p=0.0019). Prevalence of longer pain duration and increased frequency was highest amongst young adults (65.63% and 30.3% respectively). Pain duration (20.41% vs 46.15%, p=0.020) and frequency (0% vs 11.11%, p=0.042) were worse in adolescents compared to pre-adolescents. No significant associations were observed between SDOH and Pain Interference. Pain-specific PROs are worse in the AYA period with increases in pain duration and frequency in pre-adolescence. Longitudinal studies are needed to define pain trajectories and guide early interventions.

Alterations in the intestinal microbiota (dysbiosis) are a known driver of chronic inflammation. Dysbiosis leads to a “leaky” intestinal barrier triggering bacterial translocation into the blood, recurrent systemic microbial antigen exposure, and subsequent chronic inflammation. Dysbiosis plays a role in many chronic inflammatory and immune-mediated disorders, however, this process has been minimally explored in sickle cell disease (SCD). Individuals with SCD have disease-related risk factors for dysbiosis such as daily prophylactic antibiotics started in infancy, recurrent opioid therapy, and intestinal ischemia from chronic vaso-occlusion. To date, microbiome studies in SCD have been limited to small sample sizes, do not include related and unrelated Black controls, and have not assessed the impact of covariates on dysbiosis. Thus, we sought to determine intestinal microbiota differences between individuals with SCD and related and unrelated Black controls, while controlling for known covariates present in SCD and controls that can affect dysbiosis. We conducted a cross-sectional multi-site study. Individuals ≥2 months with SCD in baseline health (no acute care visits for ≥2 weeks) and healthy Black individuals (related and unrelated to those in SCD cohort) were enrolled. Ineligible individuals were those with SCD on chronic transfusions and controls with a known chronic inflammatory disorder. Stool samples were collected, microbial DNA extracted, and 16S rDNA sequencing completed. Alpha diversity (measure of microbial diversity within samples) was compared using a Kruskal Wallis test among 3 groups (SCD, related control, unrelated control) via the Shannon Diversity Index that incorporates evenness and richness of identified organisms; lower index indicates decreased alpha diversity. Beta diversity (measure of microbial diversity between groups) was assessed using Unweighted UniFrac method and the Adonis multivariable permutation test to determine if the covariates of interest explained the observed variability across the 3 groups. Covariates were site of collection, age (years), sex, mode of birth (vaginal, c-section), infant feeding (formula, breastfed), relatedness, area deprivation index (national rank), and participant group (SCD, related control, unrelated control). Significance level was p<0.05. We enrolled 110 individuals with SCD in baseline health, 53 related and 77 unrelated healthy Black individuals. Mean (SD) age (years) and sex (% female) of the groups were: SCD 16.5 (13.4), 46.4%; related controls 28.7 (12.2), 75.5%; unrelated controls 27.3 (16.9), 71.4%. SCD genotype distribution was HbSS 65.5%, HbSC 27.3%, HbSβ0thal 1.8%, HbSβ+thal 5.5%. The Shannon Diversity Index (alpha diversity) was significantly different across the 3 groups (0.000000813). Pairwise analyses for Shannon Diversity Index showed SCD was significantly lower than related (p=0.000146) and unrelated (p=1.12E-06) controls; there were no differences between related and unrelated controls (p= 0.820967). Beta diversity was also significantly different between groups as assessed by Unweighted UniFrac. Specifically, participant group was a significant variable that explained the variation between groups (R2=1.1%, p=0.027) after adjusting for site (R2=0.68%, p=0.013), age (R2=1.2%, p=0.001), infant feeding (R2=1.9%, p=0.004), and relatedness (R2=73%, p=0.001). Sex, mode of birth, and area deprivation index were not significant. In this large cohort study, we found individuals with SCD have lower intestinal microbial diversity. The lack of differences between related and unrelated controls supports SCD-related factors are driving observed intestinal microbial changes. Despite relatedness explaining a significant amount of beta diversity variation, having SCD continued to be significant, providing further evidence that SCD-related factors contribute to intestinal microbial changes. The beta diversity findings support observed microbiota differences in SCD are driven by microbial taxa, not abundance, differences. Further work is needed to assess which taxa are differentially abundant between SCD and controls, whether microbiota changes are related to SCD complications, what SCD-related factors (e.g., prophylactic antibiotics) contribute to these changes, and whether the intestinal microbiome could be a novel target for disease modifying therapy.

Background: Increasing evidence shows that adequate and balanced consumption of vital nutrients in the daily diet plays a role in promoting health and may alter the pathogenesis and progression of many diseases. Systematic nutrition assessment in individuals with sickle cell disease (SCD) is largely unexplored and thus it is not well understood how diet impacts SCD complications and health outcomes. Therefore, the objective of this study was to complete a systematic assessment of dietary nutrients consumed in individuals with SCD and determine how this consumption compares to national dietary recommendations. Methods: We conducted a cross-sectional multi-site study of individuals with SCD ≥ 2 years. Dietary data were collected during routine clinic visits using the Food Screener (age 2-11.99 parent proxy, 12-17.99 self-report) and the Block Food and Activity Questionnaire (Block 2014 Adults) (age ≥18 years). The completed questionnaires were sent to the developers for quantification of nutrients that were used for further analysis. Dietary Guidelines for Americans 2020-2025 were used as our reference to determine whether individuals consumed the ‘adequate’ amount of specific macronutrients, minerals, and vitamins in their diet. Dietary Guidelines for Americans are a science-based resource published by the U.S. Departments of Agriculture and Health and Human Services that is focused on nutritional recommendations that promote health and reduce the risk of chronic diseases. These guidelines, updated every 5 years, include the recommended intake of macronutrients, minerals, and vitamins stratified by age and sex. We assessed nutrition for each study participant by determining if their reported intake of each nutrient met the recommended intake as per Dietary Guidelines for Americans based on their age and sex (designated yes/no). We then determined the proportion of individuals in the study cohort who achieved ‘adequate’ intake for each nutrient. We assessed a total of 21 nutrients: protein, carbohydrates, fiber, calcium, iron, magnesium, phosphate, potassium, sodium, zinc, thiamin, riboflavin, niacin, vitamin A, vitamin E, vitamin D, vitamin C, vitamin B6, vitamin B12, vitamin K, and folate equivalents. Descriptive statistics were used to assess the proportion of our combined cohort (children and adults) that consumed the ‘adequate’ amount of specific nutrients in their diet. We further describe the nutrients that were adequately consumed by 50% or more or less than 50% of the cohort. Results: A total of 126 individuals with SCD were enrolled across the lifespan; 73% (n=92) were children ages 2-18 years, and 27% (n=34) were adults ages >18 years. Mean (SD) age for the entire study population was 15.3 (12.8) years; mean age for those 2-18 years was 8.6 (4.9) years and for those >18 was 33.2 (10.2) years. Of the entire study population, 46.8% (n=59) were female and distribution of genotype was HbSS 67.5%, HbSC 26.1%, HbSβ0thal 1.6%, and HbSβ+thal 4.8%. The following nutrients were consumed in adequate amounts by ≥50% of the study cohort; the exact proportion that met adequate consumption is in parentheses: protein (74.6%), carbohydrates (60.3%), sodium (57.1%), zinc (54.8%), thiamin (65.9%), riboflavin (72.2%) niacin (74.6%), vitamin B6 (75.4%), vitamin B12 (81.7%), vitamin K (52.4%), vitamin C (69%), and folate equivalents (60.3%). The following nutrients were consumed in adequate amounts by <50% of the study cohort: fiber (7.1%), calcium (21.4%), iron (46.8%), magnesium (31.7%), phosphate (48.4%), potassium (27.8%), vitamin A (33.3%), vitamin E (6.3%), and vitamin D (0.0%). Conclusions: Data show that the consumption of key nutrients including those needed for adequate bone health such as calcium and vitamin D are lacking in a large proportion of individuals with SCD. These data suggest that targeted dietary counseling is needed for individuals with SCD to ensure adequate dietary consumption as per national recommendations. Further work is needed to compare reported nutrient consumption with objective measures of physiologic levels of macronutrients, minerals, and vitamins. Ultimately, future works should explore whether nutrition is associated with SCD-related complications and whether it could be a target for interventions.

Acute and chronic pain are the most common complications of sickle cell disease (SCD). As children transition into young adulthood, SCD-related pain may change or worsen. While acute intermittent pain events are predominantly experienced by younger children, chronic pain emerges in adolescents and the prevalence of chronic pain increases with age. The ability to evaluate pain across the lifespan in SCD utilizing the same patient-reported outcome measure (PRO) is critical to understanding the SCD pain continuum as it progresses and evolves with age. To understand the impact of SCD pain across the lifespan, we sought to utilize pain-specific PROs to characterize pain in both pediatric and adult age groups. We hypothesized adults with SCD will have worse pain-specific PRO scores compared to children with SCD. A cross-sectional single-institution study was conducted of pediatric and adult individuals with SCD during baseline state of health, defined as the absence of acute care utilization for at least 2 weeks prior to data collection. Individuals ≥8 years of age self-reported PROs using the Patient Reported Outcomes Measurement Information System (PROMIS). The specific measures completed were Pain Interference, Pain Behavior, Pain Intensity, and Global Health. PROMIS is a publicly available platform that includes validated PRO tools to evaluate physical, mental, and social health in children and adults. PROMIS measures are used in the general healthy population and in those living with a chronic illness. PROMIS uses a T-score metric in which 50 is the mean of the reference population and 10 is the standard deviation of that population. For the measures included in the study, higher scores indicate worse health. Pediatric T-scores generated from the PROMIS Pain Interference measure were converted to adult T-scores per the published conversion formula. Participants were classified into two groups: Pediatric (age 8-17.99 years) and Adult (≥18 years). The PROMIS Global Health measure was categorized into three groups: Excellent/Very Good, Good, and Fair/Poor. PRO scores were compared between the two age groups using t-test for T-scores and chi-square for proportions. Significance level was set at p<0.05. A total of 79 individuals with SCD were included in the study cohort; 48 in the pediatric group and 31 in the adult group. For the pediatric group, mean age was 12 (SD=3) years and 43.8% (n=21) were female. For the adult group, mean age was 36 (SD=12) years and 54% (n=17) were female. Across the age groups, 70.8% (n=34) of children/adolescents and 48.4% (n=15) of adults had HbSS/Sβ0thal genotypes and 29.2% (n=14) of children/adolescents and 51.6% (n=16) of adults had HbSC/Sβ+thal genotypes. For all pain-specific PROMIS PROs, mean scores were significantly higher in adults as compared to the pediatric group. Specifically, adults had significantly higher mean scores on the Pain Interference (59.1 (SD 9.5) vs. 51.5 (SD 7.2), p=0.0001), Pain Behavior (58.5 (SD 9.3) vs. 37.9 (SD 12.8), p<0.0001), and Pain Intensity (4.4 (SD 2.8) vs. 2.1 (SD 2.6), p=0.0003) measures as compared to children/adolescents. There were also significant differences on the Global Health Measure between the adult and pediatric groups (overall p=0.0132). Specifically, a significantly higher proportion of adults reported their health as Fair/Poor as compared to the pediatric group (50.0% vs 18.8%, Bonferroni adjusted p = 0.001). Pain-specific PROs are worse in adults with SCD compared to children and adolescents, indicating more impairment in pain-related functioning, a higher degree of external manifestation of pain, and increased pain intensity. Additionally, Global Health scores demonstrate adults with SCD view their overall health significantly worse as compared to children and adolescents. Our data also demonstrate that pain-specific PROs are valuable tools that can be utilized to assess SCD pain across the lifespan. Future SCD pain-related research is needed to investigate pain longitudinally in individuals across the lifespan. This future work is vital to capturing the critical period during the transition from adolescence to adulthood when chronic SCD pain begins to evolve.

BackgroundHydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. ObjectiveThe goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. MethodsRecruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. ResultsTotal enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P<.001). ConclusionsWe found that timely adaptation in recruitment strategies secured high recruitment rates using an assortment of enriched remote recruitment strategies. Flexibility in approach and reducing the burden of enrollment procedures for participants aided enrollment. It is important to continue identifying effective recruitment strategies in studies involving patients with SCD and their providers and the impact and navigation of recruitment challenges. Trial RegistrationClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351 International Registered Report Identifier (IRRID)RR2-10.2196/16319

Abstract: Individuals with sickle cell disease (SCD) face the burden of managing a lifelong chronic illness, increasing vulnerability to social determinants of health (SDoH). However, how SDoH contributes to health disparities is understudied. We hypothesized that preschool children with SCD living in poor neighborhoods with higher socio-economic distress would experience increased acute care utilization (ACU; described as emergency department visits plus hospitalizations) despite disease-modifying therapy. Participants' home addresses (aged 0-6 years) were mapped using census tract environmental data from the US Department of Agriculture Food Access Research Atlas. In multivariable analyses controlled for sickle genotype and disease-modifying therapies (hydroxyurea and chronic transfusion), SDoH indicators, that is, limited access to food, lack of vehicle, low income, and inadequate education, were associated with higher ACU. Living in households with children >1 mile from a supermarket was associated with more hospitalizations (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.13-1.85) and ACU (OR, 1.37; 95% CI, 1.06-1.80) among children with SCD (aged <6 years). In households with at least 1 bachelor's degree, children with SCD experienced less ACU (OR, 0.67; 95% CI, 0.50-0.93) and hospitalizations (OR, 0.67; 95% CI, 0.49-0.92). Preschool children with SCD with limited access to food and transportation are at a higher risk of acute complications despite receiving free evidence-based therapy and social support. The family education level may have a protective effect. Although SDoH in crowded households and health care maintenance visits were not a focus of this study, future research should consider these factors. Understanding the SCD and SDoH association is crucial for directing resources to improve affected children's health.

Background: Pain in sickle cell disease (SCD) is the most visible symptom in patients. Many recent studies have shown that socio-economic status such as low income, educational achievement or even less affluent neighborhoods may contribute to the pain experience, with those of lower socioeconomic status (SES) reporting both acute and chronic pain more frequently. Furthermore, living in a less affluent area was associated with frequent use of analgesics after adjustment for pain intensity. The relationships between SES variables, pain-related anxiety, frequency of vaso-occlusive crises and/or acute care utilization have been explored; nevertheless, the relationship between SES and quality of life pain-related measures (pain hurt, pain interference, etc.) has yet to be reported. Methods: The St. Jude Children's Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) is an observation cohort study of clinical outcomes in patients with SCD. Patients enrolled in SCCRIP were retrospectively evaluated based on various SES measurements. Household SES was evaluated using the Barratt Simplified Measure of Social Status (BSMSS), a composite index of parent education and occupation. The Social Vulnerability Index (SVI) was used to classify individuals based on social vulnerabilities at the neighborhood level. The area deprivation index (ADI) ranks neighborhood in a region of interest based on social risk factors that may predispose individuals to worse clinical outcomes Quality of life measures, Pain Hurt, Pain Impact, and Pain Management/Control, were extracted from the PedsQL SCD Module. High scores on the SVI and ADI are associated with low SES and high scores on the PedsQL indicate better SCD related quality of life (QoL) with lower burden and impact of pain on function. Multivariate linear regression models were used to evaluate the associations of SES with QoL pain-related outcomes, based on a stepwise model selection strategy, with potential covariates including age, gender, disease-modifying therapy (e.g., Hydroxyurea and chronic transfusions), hemoglobin, hemoglobin F (HbF)%, and each SES variable. Results: 944 patients between the ages of 5-61 (Mean=13.75, Standard Deviation=7.57) years diagnosed with SCD completed PedsQL testing and were assessed for SVI and ADI. Multivariate models demonstrated that patients with lower SVI (i.e., higher neighborhood SES) at the neighborhood level displayed higher scores with regards to Pain Hurt (est=-7.44, standard error (SE)=2.84, p=0.01), Pain Impact (est=-9.56, SE=3.18, p=0.003) and Pain Management/Control (est=-9.35, SE=3.81, p=0.01). Similar relationships were observed for patients with lower ADI. Additionally, there was a significant association between pain impact and BSMSS (est=0.20, SE=0.10, p=0.04), suggesting that individuals with higher BSMSS (higher household SES) also had higher pain impact scores (better quality of life). Conclusions: This study demonstrated that neighborhood and household SES have an impact on pain experience in youth with SCD. Patients with increased social vulnerability and area deprivation experienced lower health-related quality of life-related to SCD pain. Increased household SES was associated with greater SCD pain impact independent of the effects of patient age, gender, SCD therapy, and HbF. Our study suggests that social determinants of health, such as SES, play a role in pain experience and QOL related to SCD pain and should be explored further.

Chronic pain affects 30% to 40% of individuals with sickle cell disease (SCD) and impairs patient functioning. Clinically meaningful, practical, and valid assessment tools for investigation, evaluation, and management of chronic pain are limited, representing a barrier for advancing SCD care. We sought to determine whether patient-reported outcomes (PROs) show preliminary construct validity in identifying individuals with SCD who were a priori defined as suggestive of having chronic pain based on previously published criteria. All individuals completed the Patient-Reported Outcomes Measurement Information System (PROMIS) domains: pain interference, pain behavior, pain quality (nociceptive, neuropathic), fatigue, sleep disturbance, depression, and anxiety; the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) domains: pain impact and emotional impact; and the painDETECT questionnaire. Thirty-three adults living with SCD were enrolled, and 42.4% had chronic pain. Pain-related PROs scores distinctly differentiated individuals with chronic pain from those without. Individuals with chronic pain had significantly worse pain-related PROs scores: PROMIS pain interference (64.2 vs 54.3), PROMIS pain behavior (63.2 vs 50), and ASCQ-Me pain impact (42.9 vs 53.2). According to published PROMIS clinical cut scores for the pain-related domains, individuals with chronic pain were categorized as having moderate impairment, whereas those without chronic pain had mild or no impairment. Individuals with chronic pain had PRO pain features consistent with neuropathic pain and worse scores in fatigue, depression, sleep disturbance, and emotional impact. Pain-related PROs show preliminary construct validity in differentiating individuals with and without chronic SCD pain and could be used as valuable tools for research and clinical monitoring of chronic pain.

Background Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. Objective The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. Methods Recruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. Results Total enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P<.001). Conclusions We found that timely adaptation in recruitment strategies secured high recruitment rates using an assortment of enriched remote recruitment strategies. Flexibility in approach and reducing the burden of enrollment procedures for participants aided enrollment. It is important to continue identifying effective recruitment strategies in studies involving patients with SCD and their providers and the impact and navigation of recruitment challenges. Trial Registration ClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351 International Registered Report Identifier (IRRID) RR2-10.2196/16319

In high-income countries, premarital genetic counseling for Sickle Cell Disease (SCD) is a standard practice. However, in Nigeria, there is no formal premarital genetic counseling program available for SCD. We conducted a series of focus group discussions with health care professionals, patients with SCD, and parents of the patients with or without SCD to gain an understanding of their attitudes and beliefs towards SCD/Sickle Cell Trait and premarital genetic counseling for SCD. Data were analyzed using Charmaz’s constructivist grounded theory approach. Two themes were highlighted in the analysis as follows: (1) the difference between the perception of premarital sickle cell screening among individuals with SCD versus the general population, and (2) the personal beliefs and physical challenges that could lead to the avoidance of premarital screening within the general community. Lack of disease-related knowledge, testing facilities, transportation, and stigma associated with the disease were the most commonly perceived barriers to premarital testing. Also, a willingness to receive premarital testing for SCD exists within our community to reduce the spread of the disease and advocate for improved health-related quality of life of patients with SCD. The content and structure of a premarital genetic counseling program in Kano, Northern Nigeria, needs to be developed.

Social determinants of health (SDoH) may impact outcomes in sickle cell disease (SCD). We conducted a comprehensive literature review of five electronic databases to elucidate the relationship between SDoH and SCD, and identify gaps in the literature. Our search yielded 59 articles, which we organized into five SDoH areas: Neighborhood and Built Environment, Health and Healthcare, Social and Community Context, Education, and Economic Stability. We found that social determinants, such as access to healthcare, were inconsistently evaluated. Improved recognition and understanding of SDoH should enhance the development of programs that directly address its detrimental effects on patients with SCD.

Increasing evidence shows that nutrition plays a role in the pathogenesis and progression of many diseases. Certain diets are shown to play a role in driving systemic inflammation and consequently contribute to exacerbation of disease processes. Systematic nutrition assessment in individuals with sickle cell disease (SCD) is largely unexplored and thus it is not well understood how diet impacts SCD complications and health outcomes. Therefore, the objective of this study was to assess both the inflammatory nature and quality of diet in adults with SCD. Individuals with SCD age ≥18 years were eligible for enrollment. Consented participants completed the validated diet assessment, the Block 2014 Food Frequency Questionnaire. This questionnaire has a recall period of one year and includes questions on the intake of 127 food and beverage items. Data collected from this questionnaire are sent to the developer for secondary and tertiary analyses for quantification of nutrients and food groups and the returned quantifications were used to calculate the Dietary Inflammatory Index (DII) and the Healthy Eating Index (HEI). The DII is a validated measure that quantifies the inflammatory nature of individuals' diet based on the potential of nutrients to trigger inflammation, whereas the HEI is a metric that assesses overall diet quality and several individual dietary components. DII is calculated based on the global mean intake and standard deviation (SD), and overall inflammatory effect score for specific food parameters. A total of 30 food parameters (Figure 1) were used for DII calculation in this study. Global mean intake and SD are used to calculate a Z-score for each nutrient which is then converted to the centered percentile. It is then multiplied with the overall food parameter-specific inflammatory effect score from the DII database to get a DII for each nutrient. These individual nutrient scores are summed to create the 'overall DII score' for an individual. Possible overall DII scores range from -8.87 to +7.98, with negative scores indicating an anti-inflammatory diet and positive scores indicating a pro-inflammatory diet. The HEI reflects adherence to Dietary Guidelines for Americans (DGA) and considers density-based (amounts per 1,000 kcal) intake of the following 13 components: total fruits, whole fruits, total vegetables, greens and beans, whole grains, dairy, total protein foods, seafood and plant proteins, fatty acids, refined grains, sodium, added sugars, saturated fats. Fruits, vegetables, and proteins are assigned a maximum of 5 points each because they are represented by two components (i.e., total fruits and whole fruits) while other food groups receive a maximum of 10 points because they are represented by one component. Maximum points are assigned if the a priori set thresholds for the specific components are met (detailed in Figure 2 legend). Final HEI is a sum of scores for each component. The HEI has a range of 0 (reflecting no adherence to DGA) to 100 (reflecting complete adherence to DGA). The mean HEI for Americans aged 19-59 years old is 57. We report the range and mean for both the DII and HEI indices. A total of 28 adults with SCD completed the Block Food Frequency questionnaire. Mean age of participants was 33.7 (SD 10.5) years with range of 19-58 years and 46.4% (n=13) were female. Figure 1 represents the DII scores for our study cohort. We found 25% (n=7) of individuals had a negative DII indicating consumption of an anti-inflammatory diet, and 75% (n=21) of individuals had a positive DII indicating consumption of a pro-inflammatory diet. The DII ranged from -5.25 to 6.55, with a median DII of 2.62 (IQR -0.49, 4.45). The mean HEI score for the study cohort was 60. Individual components of the mean HEI for SCD individuals and for average adult Americans are shown in Figure 2. Numbers in the radar graph represent the percentage of maximum possible score for each component. The majority of adults with SCD in our cohort have evidence of a pro-inflammatory diet. Our cohort had a similar HEI to average Americans, but its components vary between the food groups and require further assessment. These data are the first step to systematically assessing nutrition in individuals with SCD. Further research is necessary to investigate if nutrition impacts disease expression and health outcomes in SCD and determine whether diet is a modifiable target for interventions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chronic pain occurs in about 40% of individuals with sickle cell disease (SCD) and can significantly impair patient functioning. Neuropathic pain, defined as pain initiated by dysfunction of the peripheral and/or central nervous system, also plays a role in SCD pain. Despite this knowledge, there are minimal data evaluating patient reported outcomes (PROs) for individuals with SCD who have chronic pain. Further, data supporting the contribution of the neuropathic component to chronic pain in SCD are not well described. The objective of this study was to compare PROs between individuals with SCD who have chronic pain and those who do not. We hypothesized that PROs in individuals with SCD who have chronic pain will indicate worse patient functioning and those with chronic pain will have a more neuropathic component compared to individuals without chronic pain. Individuals ≥18 years with SCD were eligible for inclusion. Individuals reported the number of days of pain in the past month and were considered to have chronic pain if they had pain every day, 5-6 times a week, 3-4 times a week or more than 10 times a month for at least the past 6 months. We based these diagnostic criteria on those defined by the America Pain Society Pain Taxonomy Initiative for chronic SCD pain. Individuals were assessed during their baseline state of health. All individuals completed Patient Reported Outcomes Measurement Information System (PROMIS) PROs including domains of Fatigue, Sleep Disturbance, Depression, Anxiety, Pain Interference, Pain Behavior; the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) including domains of Pain Impact and Emotional Impact; and the neuropathic pain screening tool, painDETECT questionnaire. PROMIS and ASCQ-Me scoring uses a T-score metric where 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. Higher T-scores for PROMIS modules indicate more of the concept being measured (e.g. higher T-score for the domain of Pain Interference indicates higher interference due to pain). On the contrary, higher ASCQ-Me T-Scores for the Emotional and Pain Impact domains indicate better self-reported health. painDETECT scores range from -1 to 38 with higher score indicating increased probability of neuropathic pain. Further, scores 19-38 indicate a definite neuropathic pain component, 13-18 indicate a probable neuropathic pain component, and 0-12 indicate a neuropathic pain component does not exist. We compared PROMIS and ASCQ-Me domain T-scores and painDETECT scores between individuals who have chronic pain and those who do not using independent samples students t-test. A p-value of <0.05 was considered significant. A total of 30 adults living with SCD were enrolled. The mean age of our sample population was 33.9 (SD 10.2) years with range of 19-58 years and 43.3% (n=13) were female. We found 46.7% (n=14) of the study cohort had chronic pain. There were no significant differences in sex or age between those who do and do not have chronic pain. Table 1 displays the PROMIS, ASCQ-Me, and painDETECT scores in those that do and do not have chronic pain and the differences in scores between the two groups. All PROMIS scores in individuals with chronic pain were significantly higher compared to those that did not have chronic pain suggesting impaired functioning in the chronic pain cohort for the domains assessed. Further, all ASCQ-Me scores were significantly lower in individuals with chronic pain, also suggesting impaired pain and emotional functioning. Finally, painDETECT scores were significantly higher in patients with chronic pain, suggesting that neuropathic pain may be more likely to exist in those with chronic pain. PROs are significantly worse in adults with SCD who have chronic pain as compared to those who do not have chronic pain, indicating substantially impaired functioning associated with chronic pain in multiple domains and highlighting the need for multidisciplinary care for chronic pain. Neuropathic pain also appears to be more prevalent in those with chronic pain suggesting targeted treatment for this type of pain may improve patient functioning. Future work is needed to validate the use of PROs as chronic pain assessment tools. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal