Sickle Cell Disease Implementation Consortium Research Articles

Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

Social determinants of health and treatment center affiliation: analysis from the sickle cell disease implementation consortium registry

BackgroundAdults with sickle cell disease (SCD) suffer early mortality and high morbidity. Many are not affiliated with SCD centers, defined as no ambulatory visit with a SCD specialist in 2 years. Negative social determinants of health (SDOH) can impair access to care. Hypothesis: Negative SDOH are more likely to be experienced by unaffiliated adults than adults who regularly receive expert SCD care.MethodsCross-sectional analysis of the SCD Implementation Consortium (SCDIC) Registry, a convenience sample at 8 academic SCD centers in 2017–2019. A Distressed Communities Index (DCI) score was assigned to each registry member’s zip code. Insurance status and other barriers to care were self-reported. Most patients were enrolled in the clinic or hospital setting.ResultsThe SCDIC Registry enrolled 288 Unaffiliated and 2110 Affiliated SCD patients, ages 15-45y. The highest DCI quintile accounted for 39% of both Unaffiliated and Affiliated patients. Lack of health insurance was reported by 19% of Unaffiliated versus 7% of Affiliated patients. The most frequently selected barriers to care for both groups were “previous bad experience with the healthcare system” (40%) and “Worry about Cost” (17%). SCD co-morbidities had no straightforward trend of association with Unaffiliated status. The 8 sites’ results varied.ConclusionThe DCI economic measure of SDOH was not associated with Unaffiliated status of patients recruited in the health care delivery setting. SCDIC Registrants reside in more distressed communities than other Americans. Other SDOH themes of affordability and negative experiences might contribute to Unaffiliated status. Recruiting Unaffiliated SCD patients to care might benefit from systems adopting value-based patient-centered solutions.

Associations between Epigenetic Age Acceleration and Psychoneurological Symptoms in Sickle Cell Disease

Introduction: Sickle cell disease (SCD) affects approximately 100,000 predominantly Black or African American individuals in the United States. The disease has several acute and chronic complications that lead to a reduced median lifespan of 42 years, which is significantly shorter than the general US population. In this shortened lifespan, people experience deleterious psychoneurological symptoms including pain, sleep disturbances, depressive symptoms, and cognitive impairment. The high occurrence of these symptoms has negative effects on quality of life and function, and contributes to health disparities in this population. Evidence suggests a person's epigenetic age may be associated with inter-individual variability in psychoneurological symptoms in SCD. Epigenetic age is a promising biomarker because it reflects the cumulative effects of exposures to stressors at the psychosocial, physical and environmental level, by capturing the molecular processes occurring with declining tissue function through globally assessing DNA methylation patterns that account for the pace of cellular aging. Epigenetic age and age acceleration in relation to disease characteristics and symptom burden has been assessed in several chronic conditions such as cancer, obesity and Alzheimer's. None have assessed this association in SCD. To address this gap, our study aims to determine whether epigenetic age acceleration is associated with psychoneurological symptom burden (pain impact, emotional impact, sleep impact, and cognition) in SCD. Methods: Psychoneurological symptoms and DNA methylation were assessed in a subset of participants aged between 18 - 45 years enrolled in one of the Sickle Cell Disease Implementation Consortium sites. DNA methylation data were generated on the Infinium MethylationEPIC beadchip (Illumina) from the extracted DNA of blood specimens and used to calculate epigenetic age using five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, & DunedinPACE). Psychoneurological symptoms were evaluated using validated instruments: the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and Quality of Life in Neurological Disorders (NeuroQoL). Data were converted to T-scores and were used to determine associations with epigenetic age acceleration for each of the epigenetic clocks. Higher T-scores in ASCQ-Me and NeuroQoL indicate more desirable (better) outcomes. Results: Among participants (n=89) included in the analysis, the mean (SD) chronologic age was 30.6 (8.0) years. A majority identified as female (60.7%), non-Hispanic Black or African American (92%), never married (76.4%), had Hb SS genotype (68.5%), were taking hydroxyurea (60.5%), and had at least 4 pain events in past year (53.5%). Two epigenetic clocks showed mean age acceleration (Horvath: 0.2 ±4.6 years; GrimAge: 12.6 ±4.0 years, whereas two clocks showed mean age deceleration (Hannum: -4.27 ±3.91 years; PhenoAge: -8.43 ±6.0 years). The DunedinPACE clock is on a different scale than other clocks, but also demonstrated evidence for accelerated aging whereby the epigenetic age increased 1.14 years for every chronologic year. Increased age acceleration was associated with worse pain impact scores (GrimAge β=-0.25, p= 0.02), worse emotional impact scores (GrimAge β=-0.24, p=0.03; Dunedin β= -0.30, p=0.01) greater sleep disturbance (Dunedin β=-0.22, p=0.04) and more depressive symptoms (Dunedin β=0.29, p=0.01) (Table 1). Conclusion: This was the first study, to our knowledge, that explored the relationship between epigenetic age and psychoneurological symptoms in SCD. Epigenetic age acceleration was associated with worse symptom scores. Our preliminary findings identified several variations in the associations between symptom outcomes and epigenetic age across the five clocks. These variations may be due to the differences in the models used to develop the clocks, as well as inherent differences in epigenetic loci used to calculate epigenetic age for each clock. Future assessment of those discrepancies is warranted to effectively characterize individuals at higher risk of age acceleration and higher symptom burden in SCD. Our findings also highlight the potential use of epigenetic age acceleration as a biological target for interventions aimed towards preventing age acceleration and symptom development, improving the quality of life of individuals with SCD.

Impact of an Individualized Pain Plan (IPP) for Adults with Sickle Cell Disease Experiencing a Vaso-Occlusive Episode (VOE) on Patient Satisfaction and ED Provider Confidence in Treating Pain

Introduction The leading cause of Emergency Department (ED) visits among individuals with sickle cell disease (SCD) is acute pain vaso-occlusive episodes (VOE's). NHLBI guidelines recommend treatment with individualized pain plans (IPP's). To facilitate the uptake of IPP's, the National Heart Lung and Blood Institute funded eight centers across the US to participate in the Sickle Cell Disease Implementation Consortium (SCDIC). We report findings from one of the consortium's implementation projects: An Individualized Pain Plan with Patient and Provider Access for Emergency Department Care of Sickle Cell Disease (ALIGN). In ALIGN, the SCD specialist developed individualized pain plans (IPPs) for ED providers via the electronic health record (EHR) and patients via their patient portal in a phone app. We assessed changes in patient satisfaction with ED care and ED provider comfort in managing VOE after a recent visit between baseline and after IPP implementation for ED providers and patients. We hypothesized an improvement of 0.5 standard deviations in patient satisfaction from baseline to after the implementation of IPPs. We also assessed patient and provider willingness to use IPPs in the EHR and patient portal. Methods Patients and providers were enrolled from the eight SCDIC sites; six sites had IPPs already available in the EHR for ED providers, and none had IPPs available in the patient portal. Patients were eligible if they were 18-45 years old, had SCD, had access to a cell phone, had an ED VOE visit 90 days before enrollment, and had an ED VOE visit to the study site's ED within one year. Provider inclusion criteria were ED physicians, nurse practitioners, and physician's assistants with access to the EHR. The SCD specialist wrote the IPP after patient enrollment. Patients completed surveys at baseline about an ED visit within the last 90 days and again after enrollment, within 96 hours after an ED visit for VOE. The surveys collected data on patient-perceived quality of care and satisfaction with the ED. Providers completed surveys at baseline and after managing an enrolled patient in the ED. The surveys collected data on provider comfort in managing VOE. Both patients and providers answered questions about their likelihood of using IPPs. Descriptive statistics were utilized to examine sociodemographic characteristics and summarize patient and provider satisfaction. Results One hundred fifty-nine patients completed the baseline and follow-up survey. Almost all were African American (95.4%), female (64.7%), and had Hb SS/Sβ 0 genotype (71.9%). Majority (57.6%) reported they were quite a bit or very much satisfied with the care they received at baseline. There was no difference in satisfaction at baseline vs post IPP implementation (P=0.3). About 77.2% of patients responded either very much or quite a bit when asked how much the ED doctors and nurses believed they had very bad SCD pain after implementing IPPs compared with 65.4% at baseline (p=0.02). Most (64.1%) patients were more or extremely likely to show the doctor their pain plan when they returned to the ED. One hundred thirty-five providers completed the baseline and at least one follow-up survey. There was no difference is provider comfortability in their ability to manage the acute VOE post IPP implementation compared to baseline (p=0.6). More than half (62.2%) could see the pain plan in the EHR and 52.38% found the IPPs extremely easy to use. Almost all (97.6%) ED providers ordered the opioids as suggested in the IPPs. Almost all (94.7%) reported they intended to use the IPPs most or all the time. Conclusion In this implementation science protocol, all eight sites successfully implemented IPPs in the EHR for ED providers and patients in their patient portal. Both patients and ED providers enthusiastically endorsed the use of IPP's, which can help guide management of VOE in any ED, regardless of the center.

Addressing Provider-Dependent Gaps in Sickle Cell Disease Care

Sickle cell disease (SCD) affects around 100,000 Americans and presents numerous health-related challenges thus necessitating effective management strategies. Educational initiatives on evidence-based intervention are known to play a crucial role in improving patient-related outcomes (PRO) and enhancing the quality of life (QOL) for individuals with SCD. Community-based hospitals face challenges in managing SCD patients. Patients who are unaffiliated with a comprehensive sickle cell center have increased healthcare utilization, readmissions, and patient dissatisfaction due to limited access to specialized services and discrepancies in care delivery. Addressing these disparities and expanding access to care is crucial in optimizing SCD management. The purpose of this exploratory observational study was to identify provider-related gaps in a community-based tertiary center. The survey assessed internal medicine trainees' and hospitalists' baseline knowledge and comfort level at a tertiary care center with a total of 304 yearly adult admissions related to SCD management. The survey was distributed through an online platform. Data was analyzed to identify trends and gaps in internal medicine providers. Our survey had a total of 30 respondents, the response rate was 39%. Most respondents (90%) had prior experience with SCD patients; however, many gaps were identified [Table 1]. 70-75% of physicians felt comfortable managing acute pain and chronic illnesses, yet only half of these providers were comfortable with managing SCD patients. While our study sample is small, similar results were noted in a study conducted in another community-based hospital in the Chicagoland area. Our study shows a similar provider-related gap in SCD care delivery. Dr. Kanter proposed a model of care delivery which is known as the “hub and spoke” model. It offers a promising solution, creating a networked system of care with a central hub and secondary spokes providing more limited services. Community-based hospital settings can serve as spokes, bringing specialized SCD care closer to patients in local areas. Hence, we propose that this model can be further modified to include provider education. This equips non-sickle cell specialists at various spokes with the necessary knowledge and skills through targeted education by sickle cell specialists at a centralized hub. Targeting provider gaps may significantly improve PRO. Our residency program hopes to establish an affiliation with the University of Illinois (UI) Health Sickle Cell Center (SCC) to help with educating trainees on SCD. The UI Health SCC was one of eight sites participating in the National Sickle Cell Disease Implementation Consortium (SCDIC) with the goal of helping patients access longitudinal care, increase hydroxyurea utilization when appropriate, and provide proper pain management in ED. They are also part of the Recruitment and Engagement in Care to Impact Practice Enhancement (RECIPE) project which focuses on patients with SCD that are unaffiliated with care centers and attempts to understand and eliminate their barriers to care. Future efforts should include implementing targeted provider education, within the context of a hub and spoke model. This may help bridge the gap in care delivery and ultimately enhance outcomes for SCD patients.

Menopause in Sickle Cell Disease: Unchartered Territory

Menopause is a natural part of every women's life, but it may also be a time of change leading to biopsychosocial complications. Perimenopause is the time during which the body transitions to menopause, marking the end of the reproductive years. The Society for Women's Health Research Menopause Working Group cites that signs of progression toward menopause such as menstrual irregularity may be noted in the 40s, but some women may notice changes as early as their mid-30s. Perimenopause can last several years. Perimenopausal care plays an important role in the promotion of healthy aging and quality of life. For some, symptoms of menopause can have a detrimental impact on quality of life and pose serious risks to bone, cardiovascular and genitourinary health. There is a paucity of literature in menopause and sickle cell disease (SCD). A longitudinal study in Brazil of 15 women with SCD and a multi-center study of hydroxycarbamide exposure and ovarian reserve by Pecker et al have both indicated that women with SCD may have early menopause. Our exploratory study sought to determine menopause health-literacy and describe bothersome menopausal symptoms in women with SCD. A multi-faceted approach (one-on-one semi-structured interview, focus group, and registry analysis) was used for this single-institution exploratory study. Individuals were recruited during their routine clinic visit. Inclusion criteria included age >30 and ongoing menstruation OR prior menstruation. Exclusion criteria included pregnancy, breast-feeding, and history of stem-cell transplant. First, a mixed-methods survey was utilized. Next, a focus group was conducted to further elicit the views of patients about menopause and the role of healthcare providers in management of menopause for individuals with SCD. The focus group discussion was transcribed and then examined for recurring themes. The individual surveys and focus groups indicated a perceived exacerbation of SCD symptoms and complications as individuals became perimenopausal. To further assess this, data from the Sickle Cell Disease Implementation Consortium (SCDIC) registry from our site was analyzed to compare healthcare utilization between age-matched males and females. A total of 17 individuals were interviewed individually with a semi-structured questionnaire during their routine clinic visit. Individuals with HbSS on hydroxyurea underwent menopause at a median age of 50 years while those on no disease modifying treatment underwent menopause at a median age of 39 years. Many patients felt uninformed about menopause. Those who felt knowledgeable about the topic received their information from their own career in healthcare, friends, family, and the internet (Table 1). The focus group consisted of 5 female participants (3 perimenopausal and 2 post-menopausal) to elicit each individual's experiences around menopause and menopause specific care. Participants indicated worsening of SCD, hot flashes, and genitourinary complaints as their most bothersome issues with menopause. Participants reported having more frequent crises as they went through the menopause transition. Overall participants indicated that, after menopause, pain crises and hot flashes improved but genitourinary symptoms persisted. In addition, participants cited frustration over inability to address menopause related symptoms with their healthcare providers and even mentioned that providers were dismissive of their symptoms or attributed them to SCD without considering menopause transition. Further information was gathered and analyzed from the SCDIC registry; results showed that non-pregnant women have increased numbers of admissions as they enter age group of 30-40 years (Poisson regression eβ [95% CI]: 1.4 [1.3-1.7], P <0.001), while admissions for men decrease as they enter age group of 30-40 years (Poisson regression eβ [95% CI]: 0.49 [0.36-0.68], P <0.001). For the 30-40 age group, women are more likely to have admissions compared to men (Table 2). This finding could potentially be related to premature menopause contributing to increased admissions. While this study is limited due to the small size and exploratory nature, our preliminary work indicates that menopause is unchartered territory, and that many gaps exist in menopause health literacy and menopause related care delivery for women with SCD. Our findings highlight the need for further research on menopause in SCD.

Examining Mental Health, Education, Employment, and Pain in Sickle Cell Disease

Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain. To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD. This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022. Electronic medical record abstraction and a participant survey provided demographic data, mental health diagnosis, and Adult Sickle Cell Quality of Life Measurement Information System pain scores. Multivariable regression was used to examine the associations of education, employment, and mental health with the main outcomes (pain frequency and pain severity). The study enrolled a total of 2264 participants aged 15 to 45 years (mean [SD] age, 27.9 [7.9] years; 1272 female participants [56.2%]) with SCD. Nearly one-half of the participant sample reported taking daily pain medication (1057 participants [47.0%]) and/or hydroxyurea use (1091 participants [49.2%]), 627 participants (28.0%) received regular blood transfusion, 457 (20.0%) had a depression diagnosis confirmed by medical record abstraction, 1789 (79.8%) reported severe pain (rated most recent pain crises as ≥7 out of 10), and 1078 (47.8%) reported more than 4 pain episodes in the prior 12 months. The mean (SD) pain frequency and severity t scores for the sample were 48.6 (11.4) and 50.3 (10.1), respectively. Educational attainment and income were not associated with increased pain frequency or severity. Unemployment (β, 2.13; 95% CI, 0.99 to 3.23; P < .001) and female sex (β, 1.78; 95% CI, 0.80 to 2.76; P < .001) were associated with increased pain frequency. Age younger than 18 years was inversely associated with pain frequency (β, -5.72; 95% CI, -7.72 to -3.72; P < .001) and pain severity (β, 5.10; 95% CI, -6.70 to -3.51; P < .001). Depression was associated with increased pain frequency (β, 2.18; 95% CI, 1.04 to 3.31; P < .001) but not pain severity. Hydroxyurea use was associated with increased pain severity (β, 1.36; 95% CI, 0.47 to 2.24; P = .003), and daily use of pain medication was associated with both increased pain frequency (β, 6.29; 95% CI, 5.28 to 7.31; P < .001) and pain severity (β, 2.87; 95% CI, 1.95 to 3.80; P < .001). These findings suggest that employment status, sex, age, and depression are associated with pain frequency among patients with SCD. Depression screening for these patients is warranted, especially among those experiencing higher pain frequency and severity. Comprehensive treatment and pain reduction must consider the full experiences of patients with SCD, including impacts on mental health.

Infertility and treatment-seeking practices among females and males with sickle cell disease in the Sickle Cell Disease Implementation Consortium registry.

To describe the prevalence of infertility and infertility treatment seeking among people enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry and identify sociodemographic and clinical correlates of infertility. Cross-sectional. The study population included 2108 women and men (≥18years of age) enrolled in the SCDIC registry who completed the fertility questionnaire. All participants who completed the infertility-specific questions were included in the analysis (1224 females; 884 males). Of these, 16.9% of males and 23.7% of females reported infertility, in contrast to rates in the general population (12% of males; 11% of females). Only 22.8% of this subgroup had sought a fertility consultation; of these, 41% received infertility testing and 58% received advice, yet only a few received specific treatment: ovulation medication (19.1%), fallopian tubal surgery (4.8%), other female treatment (17.5%), varicocelectomy (8.1%), or other male treatment (10.8%). Increasing age, employment status, and interaction between gender and single marital status are associated with reported infertility. We did not observe differences between groups relative to sickle cell disease (SCD) genotype, a broad category of self-reported hydroxyurea use any time during life, type of medical insurance, income, or education. To our knowledge, this is the first study to examine self-reported identification of and treatment for infertility among a large sample of people with SCD. These findings suggest that (a) infertility occurs at a higher rate, but fertility care treatment seeking is less frequent than in the general public; and (b) sociodemographic and clinical differences between individuals who report experiencing infertility and those who do not did not emerge in this study.

Evaluating the implementation of a multi-level mHealth study to improve hydroxyurea utilization in sickle cell disease.

Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the intervention implementation. In this report, we describe engagement with stakeholders, planning of the implementation process, and final analytical plan to evaluate the implementation outcomes. During 19 meetings, a 16-member multidisciplinary SCDIC implementation team created, conceived, and implemented a project that utilized Intervention Mapping to guide designing an intervention and its evaluation plan. The process included five steps: (1) needs assessment of low hydroxyurea utilization, (2) conceptual framework development, (3) intervention design process, (4) selection of models and frameworks, and (5) designing evaluation of the intervention implementation. Behavioral theories guided the needs assessment and the design of the multi-level mHealth intervention. In designing the evaluation approach, we combined two implementation frameworks to best account for the contextual complexity at the organizational, provider, and patient levels: (1) the Consolidated Framework for Implementation Research (CFIR) that details barriers and facilitators to implementing the mHealth intervention at multiple levels (users, organization, intervention characteristics, broader community), and (2) the Technology Acceptance Model (TAM), a conceptual model specific for explaining the intent to use new information technology (including mHealth). The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework was used to measure the outcomes. Our research project can serve as a case study of a potential approach to combining different models/frameworks to help organize and plan the evaluation of interventions to increase medication adherence. The description of our process may serve as a blueprint for future studies developing and testing new strategies to foster evidence-based treatments for individuals living with SCD.

Characterising the prevalence of overweight and obese status among adults with sickle cell disease.

Individuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient-reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20-45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9(21.1-28)kg/m2 . In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSβ+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSβ0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p=0.0003) compared to those with HbSS or HbSβ0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity-related complications that may impact SCD-related complications.

Mortality in Adults with Sickle Cell Disease: Results from the Sickle Cell Disease Implementation Consortium (SCDIC) Registry

Background. The Sickle Cell Disease Implementation Consortium (SCDIC) was funded at eight sites in the United States by the National Heart Lung and Blood Institute (NHLBI) in 2016 to use implementation science to identify and address barriers to quality care in adolescents and adults with Sickle Cell Disease (SCD). As part of the SCDIC, the centers developed a SCD registry including 2444 persons (~300/site) ages 15-45 years at time of consent. To better understand the cause of death in adults living with SCD, this project assessed clinical co-morbidities among the enrolled adolescents and adults to identify causes of mortality and evaluate whether there are any identifiable clinical phenotypes at enrollment that would predict decreased survival. Methods. At enrollment, data were collected, including patient reported demographics, and from the medical record: SCD phenotype, baseline laboratory values, comorbidities, and medication usage. Patient reported outcome (PRO) data were also collected regarding pain and quality of life. Mortality data were obtained for 84 adults who were enrolled since 2016 in the SCDIC registry. Subjects were followed for a median of 1.76 years. The relationship of clinical co-morbidities to mortality was determined using logistic regression after adjusting for SCD phenotype and age group. Specifically, a separate model was run for each co-morbidity, with SCD phenotype, age group, and the co-morbidity being retained in the model, regardless of significance. Summary statistics were calculated, including frequency and percentage for categorical variables and mean, standard deviation, median, and interquartile range (IQR) for continuous variables. Age was evaluated as a continuous and as a categorical variable (15-24, 25-34, 35-45 years). Results. A total of 2,444 registry participants were included for analysis. Eighty-four patients died over the course of the registry data collection (2017-2022), but six deaths were caused by trauma and were removed from further analysis. Baseline characteristics of the other 78 individuals who died (n=78, 3.2%) and those who are last known to be alive (n=2,360, 96.8%) are presented in Table 1. Several co-morbidities increase the odds of death, after adjusting for genotype and age group Table 2. These include, avascular necrosis in any joint (OR [95% CI], 1.87 [1.101-3.197]), chronic kidney disease (OR [95% CI], 2.14 [1.142-3.867]), end stage renal disease (OR [95% CI], 5.95 [1.856-16.249]), pulmonary arterial hypertension (OR [95% CI], 2.41 [1.385-4.124]), sarcoidosis (OR [95% CI], 18.61 [4.191-82.986]), iron overload (OR [95% CI], 2.95 [1.691-5.348]), chronic refractory pain (OR [95% CI], 2.07 [1.183-3.661]), anxiety (OR [95% CI], 2.05 [1.162-3.523]), depression (OR [95% CI], 2.02 [1.179-3.449]), and increased acute care utilization >10 hospitalizations in year prior to enrollment: 6.48 [2.400-16.998]; >10 visits to day-hospital/infusion center in year prior to enrollment: 5.11 [2.287-12.527]). Importantly, chronic pain, anxiety and depression were reported from the patient's past medical history and not abstracted from the PRO. Current use of hydroxyurea was not significant for the total study population (deaths vs survivors, p=0.0948). Among those who died, use of hydroxyurea was also non-significant for SCD phenotype [Hb SS vs Hb SC: p=0.0758 (current use), 1.000 (use within a year of death)]. Conclusion. SCD continues to reduce life expectancy for affected individuals. These findings support that clinicians and researchers still have much work to do in providing comprehensive and supportive care to prevent end-organ damage, comorbidities and SCD complications that are associated with decreased survival. These data also continue to demonstrate the need for improved mental health resources for this population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

What does it mean to be affiliated with care?: Delphi consensus on the definition of "unaffiliation" and "specialist" in sickle cell disease.

Accruing evidence reveals best practices for how to help individuals living with Sickle Cell Disease (SCD); yet, the implementation of these evidence-based practices in healthcare settings is lacking. The Sickle Cell Disease Implementation Consortium (SCDIC) is a national consortium that uses implementation science to identify and address barriers to care in SCD. The SCDIC seeks to understand how and why patients become unaffiliated from care and determine strategies to identify and connect patients to care. A challenge, however, is the lack of agreed-upon definition for what it means to be unaffiliated and what it means to be a "SCD expert provider". In this study, we conducted a Delphi process to obtain expert consensus on what it means to be an "unaffiliated patient" with SCD and to define an "SCD specialist," as no standard definition is available. Twenty-eight SCD experts participated in three rounds of questions. Consensus was defined as 80% or more of respondents agreeing. Experts reached consensus that an individual with SCD who is unaffiliated from care is "someone who has not been seen by a sickle cell specialist in at least a year." A sickle cell specialist was defined as someone with knowledge and experience in SCD. Having "knowledge" means: being knowledgeable of the 2014 NIH Guidelines, "Evidence-Based Management of SCD", trained in hydroxyurea management and transfusions, trained on screening for organ damage in SCD, trained in pain management and on SCD emergencies, and is aware of psychosocial and cognitive issues in SCD. Experiences that are expected of a SCD specialist include experience working with SCD patients, mentored by a SCD specialist, regular attendance at SCD conferences, and obtains continuing medical education on SCD every 2 years." The results have strong implications for future research, practice, and policy related to SCD by helping to lay a foundation for an new area of research (e.g., to identify subpopulations of unaffiliation and targeted interventions) and policies that support reaffiliation and increase accessibility to quality care.

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model

PurposeTo examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 – 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains.MethodsParticipants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare.ResultsHigher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02–1.10, 95% CI range [1.004–1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58–3.28 95% CI range [1.18–4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46–0.64, 95% CI range [0.34–0.86]).ConclusionsStudy results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes.

Pregnancy outcomes with hydroxyurea use in women with sickle cell disease.

Hydroxyurea reduces pain crises, acute chest syndrome, and blood transfusions in sickle cell disease (SCD), but potential detrimental effects on fertility and birth outcomes impede its use. Data on the effects of hydroxyurea taken for SCD during conception and pregnancy are scarce. The Sickle Cell Disease Implementation Consortium collected self-reported pregnancy history, corresponding hydroxyurea use, and pregnancy outcomes in women with SCD in the clinical setting. Among 1285 women 18-45 years of age, 737 (57.4%) reported 1788 pregnancies (1079 live births, 394 miscarriages, 40 stillbirths, 207 abortions, 48 current pregnancies, and 20 missing outcomes) of which 241 (15.9%) live births, miscarriages or stillbirths were conceived while on hydroxyurea. In univariate analyses, pregnancy number more than three, severe sickle genotype, history of stillbirth or miscarriage, and chronic kidney disease at enrollment were covariates significantly associated with a pregnancy ending in miscarriage or stillbirth. After adjustment for covariates and additional SCD severity markers in multivariate analyses, hydroxyurea use during conception and pregnancy, but not during conception only, was associated with an increase in the odds ratio (OR) of miscarriage or stillbirth (OR 2.21, 95% confidence interval [CI] 1.40-3.47). In analyses of live birth outcomes, hydroxyurea use during conception and pregnancy was associated with birth weight < 5.5 pounds in full-term infants (OR 2.98, 95% CI 1.09-7.38) but not with prematurity or serious medical problems at birth. These findings suggest that hydroxyurea use may be safe up to the time of conception, but that clinicians should continue to advise caution regarding use during pregnancy.

Identifying barriers to evidence-based care for sickle cell disease: results from the Sickle Cell Disease Implementation Consortium cross-sectional survey of healthcare providers in the USA

ObjectivesSickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based...

Sex-based differences in the manifestations and complications of sickle cell disease: Report from the Sickle Cell Disease Implementation Consortium.

IntroductionSex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry.MethodsThe SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants’ medical records.ResultsA total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p<0.001), more vaso-occlusive episodes (p = 0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9% vs. 25.5, p = 0.03). On multivariable analysis, males had higher odds of acute chest syndrome (odds ratio (OR) 1.4, p = 0.002), cardiovascular (OR 1.70, p<0.001) and musculoskeletal (OR 1.33, p = 0.0034) complications and lower odds of depression (OR 0.77, p = 0.0381). Females had higher fetal hemoglobin levels with and without hydroxyurea use (9.6% vs 8.5%, p = 0.03 and 3% vs 2.2%, p = 0.0005, respectively).ConclusionOur data suggests that sex differences in clinical outcomes do occur among individuals with SCD. Future research needs to explore the mechanisms underlying these differences.

A Needs Assessment of Persons With Sickle Cell Disease in a Major Medical Center in North Carolina.

BACKGROUND Sickle cell disease (SCD) is a complex disease associated with many complications and a shortened lifespan. In 2016, the National Heart, Lung and Blood Institute funded 8 centers in the United States to form the Sickle Cell Disease Implementation Consortium, with the goal of improving SCD care. The aim of our study was to describe SCD self-efficacy, pain interference, and barriers to care from the perspective of persons with SCD in the North Carolina center.METHODS Persons with SCD, aged 15 and older were recruited from a large SCD center in North Carolina. Surveys, focus groups, and interviews were completed.RESULTS Fifty-one people completed a survey, and 14 people completed an interview or focus group. Barriers identified in the survey included self-care barriers, misconceptions related to hydroxyurea (an oral medication that reduces rates of pain crisis), limited provider knowledge, and stigma. Concerning self-efficacy, participants reported that they were able to manage their pain symptoms most of the time. Pain interfered most with the ability to participate in social and day-to-day activities.Common themes from the focus groups and interviews included misconceptions about hydroxyurea, pain, provider knowledge, stigma, co-management, transportation, and insurance. Recommendations to improve care included the use of case managers, utilization of treatment guidelines, individualized pain protocols, and effective co-management by providers.LIMITATIONS Participants were recruited from 1 SCD center and may not be representative of the entire SCD population in North Carolina.CONCLUSIONS Participants described many perceived barriers to care, and their responses suggest a need for improvements in patient hydroxyurea education, provider knowledge, and care coordination.

Patient-reported neurocognitive symptoms influence instrumental activities of daily living in sickle cell disease.

Individuals with sickle cell disease (SCD) experience neurocognitive decline, low medication adherence, increased unemployment, and difficulty with instrumental activities of daily living (IADL). The relationship between self-perceived cognitive difficulties and IADLs, including employment, school enrollment, independence, engagement in leisure activities, and medication adherence is unknown. We hypothesized that self-reported difficulties across neurocognitive areas would predict lower IADL skills. Adolescent and adult participants of the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) (n=2436) completed patient-reported outcome (PRO) measures of attention, executive functioning, processing speed, learning, and comprehension. Cognitive symptoms were analyzed as predictors in multivariable modeling. Outcome variables included 1) an IADL composite that consisted of employment, participation in school, reliance on others, and leisure pursuits, and 2) hydroxyurea adherence. Participants reported cognitive difficulty across areas of attention (55%), executive functioning (51%), processing speed (57%), and reading comprehension (65%). Executive dysfunction (p < 0.001) and sometimes or often experiencing learning difficulties (p < 0.001 and p=0.04) and poor comprehension (p=0.000 and p=0.001), controlled for age (p < 0.001), pain (p < 0.001), and hydroxyurea use (p=0.001), were associated with poor IADL skills. Executive functioning difficulties (p=0.021), controlled for age (p=0.013 for ages 25-34), genotype (p=0.001), and hemoglobin (p=0.004), predicted hydroxyurea non-adherence. Analysis of PRO measures indicated that cognitive dysfunction is prevalent in adolescents and adults with SCD. Cognitive dysfunction translated into clinically meaningful outcomes. PRO of cognitive symptoms can be used as an important adjunct clinical tool to monitor symptoms that impact functional skills, including engagement in societal activities and medication adherence.

Severe Persistent Pain and Inflammatory Biomarkers in Sickle Cell Disease: An Exploratory Study.

Severe pain is among the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD), of whom more than 50% report chronic pain. Despite this, the understanding of the biological contributors to persistent severe SCD pain is limited. This exploratory study sought to describe pain phenotypes based on frequency of severe pain experienced over 6 months and identify inflammatory biomarkers associated with pain phenotypes among individuals with SCD. This study used self-report and electronic health record data collected from 74 individuals enrolled in the Duke Sickle Cell Disease Implementation Consortium Registry. Plasma from previously collected blood specimens was used to generate inflammatory biomarker data using the Inflammation 20-plex ProcartaPlexTM panel. Descriptive statistics were used to describe the occurrence of severe pain over the past 6 months, and bi-variate analyses were used to evaluate the relationship between inflammatory biomarkers and pain phenotypes. Among the 74 participants included in this study, 33.8% reported severe pain occurring never or rarely, 40.5% reported severe pain occurring sometimes, and 25.7% reported severe pain occurring often or always. Soluble E-selectin (sE-selectin) was the only inflammatory biomarker significantly associated with the pain phenotype groups (p = 0.049). Post hoc comparisons identified that participants in the often/always severe pain group had significantly higher plasma concentrations of sE-selectin compared to those in the sometimes severe pain group (p = 0.040). Our findings provide preliminary evidence of the frequent occurrence of severe pain and that sE-selectin may be an objective biomarker for the frequent occurrence of severe pain in this population.

County Level Surveillance of Sickle Cell Disease Population, Healthcare Utilization, and Fragmentation to Support Improvements in Access to Care

Little is known about the health care, complications, and outcomes of those living with sickle cell disease (SCD) in the US, outside of patients seen in specialty SCD clinical settings. Adults, in particular, are less likely to be seen in specialty settings. CDC has implemented the Sickle Cell Data Collection (SCDC) program in California and Georgia to establish true population-based surveillance systems at the state level in an effort to address these gaps in knowledge. These data allow investigation of healthcare utilization and outcomes in these states for the majority of patients with SCD in all settings, even if not seen by SCD specialists.Such data can be used to identify and address specific problems, such as care fragmentation (use of multiple, unconnected facilities by high utilization patients) and lack of access to quality care. Researchers at University of California San Francisco Benioff Children's Hospital Oakland (BCHO) collaborated with SCDC to obtain aggregated data about SCD patient populations, care fragmentation, and inpatient and emergency department utilization (ED) in five Northern California counties. BCHO's goal was to obtain NHLBI grant funding through the Sickle Cell Disease Implementation Consortium (SCDIC) to support outreach and interventions for adolescent and adult patients (ages 15-45 years) seen in hospital settings but not by SCD specialists.California hospital admissions, ED and Medicaid claims data for the years 2004 through 2015 were obtained by SCDC for those with SCD ICD codes, and linked by social security number and date of birth. Patients with three or more SCD coded encounters within any five-year period were included. Data for these patients was used to determine frequency of utilization at EDs and inpatient facilities in the included counties and care fragmentation patterns to guide outreach efforts for BCHO's team. Care fragmentation is described as low if >= 90% of hospital/ED encounters were at same facility, high if under 75% were at any one facility, and medium between these cutoff points.There were 1,024 persons with recent (2013-2015) healthcare utilization (Medicaid claims, inpatient or ED) in the catchment area, ages 15-45 during the three year period (Table 1). Sixty three percent (n=493) of the identified adults and 64% (n=157) of pediatric patients had one or more ED visits or inpatient stays during the three years. Seventy three percent of the pediatric patients had low levels of care fragmentation while almost half of the adults had medium or high (Table 2). Overall, most patients (75%) were seen at one or two facilities only.Now awarded, BCHO's grant supports targeted outreach to ED facilities in these counties with a high number of patients with SCD. Providers and patients are participating in a needs assessment that will inform strategies to bring patients into specialty outpatient care, training and support for providers, and strategies to enhance disease self-management. With the goal of reducing care fragmentation and bringing more patients into care with providers knowledgeable about SCD, the primary targets of BCHO's outreach efforts are the 25 EDs and 5 inpatient facilities that are not affiliated with a SCD specialty care setting. Those facilities that had 25 or more encounters with patients with SCD in any one year (Table 1) have been approached about collaborating with the project. BCHO's secondary targets will be the 13 EDs and 29 inpatient facilities with more than one but fewer than 25 such encounters per year. Future collected data can be used to evaluate the effectiveness of the outreach and training efforts over the course of the grant. Data from public health surveillance in SCD and other rare disorders has the potential to inform specific program improvements and cross organization collaboration, leading to better outcomes for patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.