Sickle Cell Disease Community Research Articles

Dual P-Selectin and Complement Inhibition with Subcutaneous IHP-102 Treatment Potently Reduces Lung Vaso-Occlusion in Sickle Cell Disease Mice

One of the most debilitating manifestations of sickle cell disease (SCD) are the excruciatingly painful vaso-occlusive episodes (VOEs), commonly referred to as “pain crises.” Vaso-occlusion, which underlies the pathomechanism of VOE, also causes downstream tissue and organ damage resulting in complications that plummet life-expectancy by more than 20 years. Current treatment options for VOE are limited and all require chronic administration, often with intolerable side-effects, and none fully prevent VOE. An acute VOE rescue therapy that could be administered in the home-setting would transform care for the more than 100,000 people in the U.S. and over 7 million worldwide who suffer from this inherited condition. IHP-102 is a novel glycan-based drug with dual anti-P-selectin and anti-complement activity. It is bioavailable by subcutaneous route of administration and could therefore be self-administered at the earliest sign of VOE. Early intervention in VOE is critical, before ischemia and tissue damage becomes irreversible. This treatment paradigm would also circumvent the wholly inadequate treatment experience that the SCD community has widely described, being treated as an opioid “drug-seeker” when engaging the healthcare system during a debilitating VOE. There are multiple pathomechanisms of VOE. P-selectin is a clinically validated therapeutic target for partially attenuating VOE, while complement has more recently been identified as an important driver of VOE, in part due to hemolysis and ischemia. While several therapeutics targeting P-selectin or complement are currently in clinical development, no therapy targets both pathomechanisms. We have previously shown that IHP-102 inhibits P-selectin mediated cell adhesion in vitro (IC50 = 0.7 µg/mL) and that intravenous administration of IHP-102 reduces lung vaso-occlusion by 75% in Townes SCD mice challenged with oxy-hemoglobin (oxy-Hb). Here, we extend these studies with subcutaneous delivery of IHP-102, achieving greater than 75% reduction in lung vaso-occlusion. This magnitude of effect is greater than that achieved in P-selectin deficient Townes SCD mice (~50% reduction), thus indicating additional activity of IHP-102 beyond P-selectin inhibition. In studies using human serum, IHP-102 inhibits complement by upstream mechanisms, including through inhibition of Factor B. Factor B is responsible for alternative pathway amplification of complement. Its fragment Bb has been found in elevated concentrations during VOE in patient serum, suggesting it plays an important role in the pathomechanism of VOE. By inhibiting Factor B, IHP-102 reduces downstream complement fragments of C3 and C5, which are widely recognized complement targets given their critical role in the complement system and promoting inflammation. The dual anti-complement and anti-P-selectin activity of IHP-102, together with its potential for home-based treatment, offers great potential to fill a major treatment gap for acute VOE. Its potent in vivo activity suggests that this dual target approach could provide robust therapeutic benefit and warrants further investigation toward clinical trials.

Motivators and Barriers for People with Sickle Cell Disease Participating in Clinical Trials: Global Findings from the LISTEN Survey

Background: The success of clinical trials of new therapies for sickle cell disease (SCD) will depend on the recruitment and retention of a large and diverse group of people with SCD (PwS). Qualitative studies have reported barriers to participation in clinical trials, including the potential impact on health, unmanageable study demands, limited knowledge of trials, and lack of trust in healthcare(Patterson CA et al. J Pediatr Hematol Oncol 2015; Lee LH et al. Blood Adv 2021). The Learning and Insights into Sickle Cell Trial Experiences (LISTEN) Survey was developed to provide a robust and comprehensive understanding of the global barriers and motivators to participation in clinical trials for PwS. Aim: To present interim findings from the LISTEN Survey regarding participation and experiences of PwS in clinical trials, barriers and motivators to participation, and differences in responses from PwS compared with perspectives of healthcare professionals (HCPs) treating PwS. Methods: Between October 6, 2022 and June 22, 2023, a broad range of adults (≥18 years) with SCD and HCPs involved in the treatment and/or clinical research of SCD in 17 countries were asked to complete corresponding quantitative surveys. PwS were asked whether they had participated in a clinical trial and, if so, whether their experience had met their expectations. PwS were asked to rate on a 7-point scale (from not at all to extremely important) and rank (from most to least important) the importance of specified factors (grouped into five categories) when deciding whether to participate in a clinical trial for SCD. HCPs provided their perspectives on the importance of these factors to PwS. The results presented here include the total proportion of respondents who rated factors as extremely or very important and the proportion who ranked factors first or second. Results: Overall, 1028 PwS (57% female) with a median age (interquartile range) of 30 years (24-37) from 16 of the 17 countries and 361 HCPs (67% hematologists and/or SCD specialists) from 17 countries completed the survey. In total, 35% of PwS had been invited to participate in a clinical trial for SCD. In PwS who had taken part in a clinical trial (24%; n=249/1028), compared with their expectations, 36% reported a better experience, 36% the same as expected experience, 9% a worse experience, and 20% did not know what to expect. Extremely or very important factors that motivated PwS to participate in a clinical trial included the potential to better manage their symptoms (52%), the opportunity to try a new treatment that might work better (51%), and to increase their knowledge of SCD (51%; Figure 1). An important barrier to participation was the potential to experience different side effects (51%). In the trial information category, PwS ranked (first or second of five) safety measures (57%) and how the treatment works (49%) as the most important factors; these were considered to be significantly more important than who is leading (27%) or funding (24%) the trial; p<0.001 for all combinations. In the further considerations category, the majority of PwS ranked (first or second of five) speaking to other PwS involved in the trial (51%) and experts running the trial (50%) as the most important factors. HCPs overstated the potential practical barriers for PwS compared with responses from PwS, including missing school/work (50% vs 42%; p=0.009), the effort required to start the trial treatment (45% vs 32%; p<0.001), and travel requirements (52% vs 36%; p<0.001). HCPs understated the importance of wider clinical trial outcomes as motivators for PwS compared with responses from PwS, including supporting new treatment developments that may benefit them (41% vs 51%; p=0.001) or other PwS (38% vs 49%; p<0.001; Figure 2). Conclusions: Improving access and recruitment into clinical trials in SCD will require clear communication of the potential benefits to individuals and the wider SCD community, as well as potential safety and side effects. Findings from the LISTEN Survey highlight that those directly involved in the trial should deliver these messages, including other PwS who are involved in the trial. Given the disconnect between PwS and HCPs, shared decision-making may also improve understanding and increase participation in clinical trials. Further analyses of the survey results will be important to identify the differences in responses between regions, age groups, and other subpopulations.

A Collaborative Model for Improving Patient Engagement and Access for Hematopoietic Stem Cell Transplant and Clinical Gene Therapy Trials for Patients with Sickle Cell Disease in the Upper Midwest United States

Introduction: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy affecting populations across the United States. Several well-established patient-centered comprehensive care models have been in practice for preventive care and pain management. However, access to hematopoietic stem cell transplant (HSCT) and clinical trials for sickle cell gene therapies are limited, especially in pediatric and adult centers with limited HSCT-related resources. We describe a patient-centered collaborative model in the Upper Midwest United States to improve patient education and engagement as well as access to HSCT and gene therapy trials for patients with SCD. Collaborative Care Model: Since August 2021, centers across the Midwest meet monthly to improve access for HSCT and gene therapy as well as education about these therapies for individuals with SCD. The teams include: hematology and transplant teams from University of Minnesota, Comprehensive Sickle Cell Care team from Children's Hospital of Minneapolis, hematology and transplant team from Mayo Children's Hospital, hematology team from Essential Health, Duluth, Minnesota, hematology team from Sanford Children's Hospital Fargo and Sioux Falls and hematology team from Blank Children's Hospital, Des Moines, Iowa. This collaborative approach involves several stakeholders including an SCD community advocacy organization, hematology care providers across several rural as well as community/university hospitals, social workers, nurse coordinators, HSCT/gene therapy providers, as well as representatives from National Marrow Donor Program. Individual patient needs and available community support as well as institutional resources are discussed at length during monthly virtual meetings and a pre-intervention plan is established to ensure smooth transition of care to and from primary centers (Figure 1). Ongoing communication with the primary team helps with efficient transition of care after transplant as patients continue ongoing monitoring and care closer to home. Community partners help with early education of the families and provide necessary resources and support. Institutional partners like NMDP provide support with immune typing and discuss ongoing support and other resources available for providers and families. Results/Impact: Since the implementation of this collaborative model, there has been a steady increase in early referrals for education regarding HSCT and potential gene therapies trials for patients with SCD. There has been about 100% increase in new patient referrals since the implementation of this collaborative model compared to the average new referrals in the previous years (2021-22 vs 2018-19; Figure 2). Enrollment in HSCT as well as gene therapy clinical trials also has increased 2-3 folds since the implementation of the collaborative care model. It has helped established early discussion and longitudinal care and has also led to ongoing evaluation and discussions for availability of optimal donors, determining eligibility for HSCT and gene therapy trials as well as providing ongoing support and education to the sickle cell community and providers regarding the available therapies for SCD. This has also facilitated the transplant team establish earlier and better rapport with patients and their families and provide necessary education with an in-depth discussion regarding the potential benefits and risks of therapies such as HSCT and gene therapy. These discussions often occur over multiple visits and helps address psychological as well social barriers with a prospective evaluation. Additionally, the ongoing discussion among the providers helps with longitudinal monitoring of the patients and provide an assessment of the risks and benefits of therapies as the patient's disease course continues to evolve. This multi-stake holder collaborative approach continues to provide a well-established platform for discussion of newer therapies and access to open clinical trials, available resources for patients and families, and improve patient care and experience. The impact of this collaboration is noted in significant increase in early referrals and educational consults for HSCT and gene therapies, improved patient engagement as well as the acceptability and participation in clinical trials.

Looking ahead: ethical and social challenges of somatic gene therapy for sickle cell disease in Africa.

Somatic gene therapy will be one of the most exciting practices of genetic medicine in Africa and is primed to offer a "new life" for persons living with sickle cell disease (SCD). Recently, successful gene therapy trials for SCD in the USA have sparked a ray of hope within the SCD community in Africa. However, the high cost, estimated to exceed 1.5 million USD, continues to be a major concern for many stakeholders. While affordability is a key global health equity consideration, it is equally important to reflect on other ethical, legal and social issues (ELSIs) that may impact the responsible implementation of gene therapy for SCD in Africa. These include informed consent comprehension, risk of therapeutic misestimation and optimistic bias; priorities for SCD therapy trials; dearth of ethical and regulatory oversight for gene therapy in many African countries; identifying a favourable risk-benefit ratio; criteria for the selection of trial participants; decisional conflict in consent; standards of care; bounded justice; and genetic tourism. Given these ELSIs, we suggest that researchers, pharma, funders, global health agencies, ethics committees, science councils and SCD patient support/advocacy groups shouldwork together to co-develop: (1) patient-centric governance for gene therapy in Africa, (2) public engagement and education materials, and (3) decision making toolkits for trial participants. It is also critical to establish harmonised ethicaland regulatory frameworks for gene therapy in Africa, and for global health agencies to accelerate access to basic care for SCD in Africa, while simultaneously strengthening capacity for gene therapy.

Democratizing Knowledge for Sickle Cell Disease Gene Therapy: A Community Based Model for Creating Patient Education Materials

Background: While the advancement of genetic therapy for hematological disorders provides tremendous therapeutic promise, it is not without risk. Sickle cell disease (SCD) is at the forefront of the development of novel, genetic therapies. The process of engaging individuals living with SCD to participate in gene therapy clinical trials requires building trust, respect, and partnership with the community, given the history of neglect towards this disease. With the growth of sickle cell disease gene therapy clinical trials and potential of FDA approval for gene therapy treatments, there is a need for understandable, accessible, and actionable patient education materials (PEMs) that are not sponsored by a specific clinical trial. An objective of the Democratizing Knowledge for Sickle Cell Disease Gene Therapy Project was to examine the process of engaging a diverse group of stakeholders representing different interests within the SCD community to develop open-source patient education materials for sickle cell disease gene therapy. Methods: For this project, we used a community-based dialogue model which incorporates participatory democracy with community based public health engagement approaches (Bonham et al PMID: 19451407). This approach was used to engage a multi-disciplinary group of patients, representatives of SCD advocacy groups, hematologists, gene therapy researchers, and industry and government stakeholders to purposefully work in teams over four workshops to create PEMs. Throughout this process, we recorded their deliberations, and collected survey data at three distinct stages of engagement. Results: We dichotomized the data on experiences and engagement levels into two categories: the Research Community, which includes individuals representing industry, research, government, healthcare, academia, and the Patient and Advocacy Community, which includes individuals living with SCD, parents of children with SCD, and individuals representing community-based SCD advocacy groups. Analysis of this longitudinal data from the three distinct points in time identified patterns across the stakeholder groups represented in these workshops. Of the participants in the research community, 68.3% attended all four workshops, while of those in the patient and advocacy community, 90.9% attended all four workshops (Table 1). In the research community, 95.1% expressed feeling satisfied with their participation in these workshops, and similarly, in the patient and advocacy community, 93.0% expressed feeling satisfied with their participation (Table 2). However, when surveyed about views on the role of power dynamics in this process, there were differing sentiments between these two groups. Amongst the research community, the majority felt power dynamics did not influence the workshops (59.3%). In contrast, amongst the patient and advocacy community, the majority felt power dynamics did influence the workshops (55.2%) (Table 2). In addition to this survey data, further data regarding the patient educational materials themselves and their dissemination will be reported. Conclusion: The data highlights differential engagement regarding the level of participation between the different stakeholders within the SCD community. It also reflects both similarities and differences with respect to satisfaction and perception of power dynamics in this process. With these results, we aim to introduce how a community-based dialogue approach can be used as a model for engagement for SCD clinical trials, for creation of stakeholder-informed patient education materials, and for other disease communities. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

“Something with a Frightening Reputation”: 60 Minutes’ Accommodation of HIV in Gene Therapy for Sickle Cell Disease

On March 10, 2019, 60 Minutes reported the development of a potentially life-altering gene therapy for Sickle Cell Disease (SCD). Despite this therapy’s potential for cure, SCD community members’ reactions ranged from skepticism to fear due to the use of deactivated HIV as a vector for transporting the corrected gene into stem cells, thus repairing the faulty gene in SCD. Using a mental models framework, we analyze how 60 Minutes attempted to explain this research and how audiences reacted on social media. Specifically, we show how 60 Minutes’ treatment of given versus new information, as well as the journalists’ failure to account for the specific audiences with the most at stake, led to misunderstandings that contributed to ongoing fear and mistrust of the scientific community. We conclude with recommendations for how journalists should approach accommodating science when that science has particular impacts on minoritized and marginalized groups.

The Sickle Cell Disease Ontology: recent development and expansion of the universal sickle cell knowledge representation.

The Sickle Cell Disease (SCD) Ontology (SCDO, https://scdontology.h3abionet.org/) provides a comprehensive knowledge base of SCD management, systems and standardized human and machine-readable resources that unambiguously describe terminology and concepts about SCD for researchers, patients and clinicians. The SCDO was launched in 2016 and is continuously updated in quantity, as well as in quality, to effectively support the curation of SCD research, patient databasing and clinical informatics applications. SCD knowledge from the scientific literature is used to update existing SCDO terms and create new terms where necessary. Here, we report major updates to the SCDO, from December 2019 until April 2021, for promoting interoperability and facilitating SCD data harmonization, sharing and integration across different studies and for retrospective multi-site research collaborations. SCDO developers continue to collaborate with the SCD community, clinicians and researchers to improve specific ontology areas and expand standardized descriptions to conditions influencing SCD phenotypic expressions and clinical manifestations of the sickling process, e.g. thalassemias. Database URL: https://scdontology.h3abionet.org/

Process and strategies for patient engagement and outreach in the Sickle Cell Disease (SCD) community to promote clinical trial participation

IntroductionSickle cell disease (SCD) is the most common inherited blood disorder in the United States. The Cure Sickle Cell Initiative (CureSCi) was created by the National Heart, Lung and Blood Institute (NHLBI) to improve the lives of people with SCD by accelerating the advancement of safe and promising genetic therapies, engaging the SCD community and healthcare providers, and encouraging collaboration among stakeholders. CureSCi is a collaborative, patient-focused research effort that includes patients at every level of the Initiative. Patient engagement is a key component, particularly during the development of clinical trials. ObjectiveTo describe the processes and strategies utilized by the CureSCi to engage individuals living with SCD about genetic therapy clinical trials. MethodsThe CureSCi Patient Engagement team conducted nine Community Outreach visits in 2019, each of which was structured to include separate group interviews with patients and medical providers. A set of guidance questions was developed for each audience and the interviews lasted approximately 60 minutes. ResultsPatients were asked about their participation in a clinical trial, and approximately 50% had participated in a trial. SCD individuals reported trusting their medical provider to provide them with information relevant to trials. Medical providers emphasized the individual, family, and health aspects of SCD that warrant additional investigation. Providers reported barriers encountered by patients as transportation, childcare support, infertility, and trust in the healthcare system. ConclusionLessons learned from the community have helped to influence recommendations for clinical trial design and key messaging development for the Cure Sickle Cell Initiative.

P137: WHAT’S IN A NAME? PATIENTS WANT US TO RETHINK ‘SICKLE CELL DISEASE’

Racism impacts all aspects of patient care, not least for those with Sickle Cell Disease (SCD). Minimal research exists in this area, despite being long identified as a compelling issue for patients [1], and highlighted as a “Top 10” Priority in a workshop during ASCAT 2019. In response, we conducted a series of workshops to explore how race and racism impacts the quality of care in the SCD community and to identify actionable areas of change. This comprised three 90 minute sessions held over Zoom in May, June and July 2021. Attendees included people living with SCD, doctors, nurses, medical students, and members of the local community. Outcomes broadly centred around the themes of medical education; public education; and ways of better supporting the SCD patient community. However, we were struck by a rich discussion on how the name ‘Sickle Cell Disease’ may, in itself, influence the mindset of caregivers and perpetuate stigma in both clinical and social settings. The term ‘Sickle Cell Anaemia’ traditionally refers to HbSS only, though OMIM uses it to cover all genotypes [2]. Meanwhile the ICD-10 classification code D57 refers to ‘Sickle Cell Disorders’, with sub-categories using ‘Disease’ and divided by genotype [3].From the workshops, the patient group shared a strong consensus view that Sickle Cell Disorder, rather than ‘Disease’, would be preferable as a more neutral term of reference. To verify the results of the workshop in an independent sample, a questionnaire was circulated to a small SCD patient support group (12 individuals) to assess their preference for one or other label. 9/12 (75%) preferred ‘Disorder’, one preferred ‘Disease’ and two expressed no preference. Which label was used by patients themselves, their families and friends, and their medical teams was important to patients, with 67% expressing a wish that this issue be pursued further. Interestingly, the acceptability of Disorder/Disease showed some variation by the patient’s country of birth. These findings point towards a pressing need for increased sensitivity around the language used to talk about illness, particularly where the condition has been historically stigmatised.

Acceptable, hopeful, and useful: development and mixed-method evaluation of an educational tool about reproductive options for people with sickle cell disease or trait.

People with sickle cell disease (SCD) or trait have many reproductive options, some of which decrease the chance of passing SCD to children, including in vitro fertilization with preimplantation genetic testing (IVF + PGT). Few are aware of these options, and educational materials are needed. This study aimed to develop an accessible, non-directive patient education material about reproductive options for those with SCD or trait via a process that incorporated stakeholders from the SCD community. Multidisciplinary stakeholders guided development and revision of a novel pamphlet. Researchers applied health literacy scales to measure pamphlet understandability. We interviewed nine patients with SCD and six multidisciplinary clinicians to evaluate the pamphlet. Interviews were recorded, transcribed, and coded by a five-member team who developed a codebook and proposed themes that were revised by all research team members. Feedback was incorporated into a revised pamphlet. A two-page pamphlet describing reproductive options for people with SCD including IVF + PGT was acceptable to key stakeholders, including people with SCD. Material about this complex topic met health literacy standards, including being written at a 5th grade level. Patients reported feeling hopeful after reviewing the pamphlet, and participants considered the pamphlet useful, clear, and appropriate for distribution in clinics and online. Though awareness of reproductive options for those with SCD or trait is low, patients and providers find a novel pamphlet about this topic acceptable and useful. Educational materials about complex topics including IVF + PGT can be written at a level understandable to the average American.

Knowledge of Fertility and Perception of Fertility Treatment Among Adults with Sickle Cell Disease (KNOW FERTILITY)

BackgroundAdults with sickle cell disease (SCD) face unique fertility risks due to SCD and use of disease modifying therapies (DMTs). Concerns about compromising fertility may inform patients' therapy choices, but little is known about fertility knowledge in adults with SCD. The Cardiff Fertility Knowledge Scale (CFKS) and Fertility Treatment Perception Survey have been studied in international and national cohorts 1,2. The purpose of this study was to administer these surveys to adults with SCD and compare responses to previously studied populations.MethodsOur IRB approved this cross-sectional study of adults with SCD (≥18YO) cared for at our Sickle Cell Center for Adults. Due to the COVID-19 pandemic, eligible subjects were recruited during routine telemedicine clinic visits and by invitation via electronic medical record. We collected demographic information (sex, age (≥/< 31YO), educational attainment, and use of DMTs). The CFKS is a 13-question survey that measures knowledge of causes of reduced fertility, common misconceptions about fertility, and infertility facts. Questions are answered True/False/Don't know and equally weighted; the cumulative score is 0-100%. We compared the mean CFKS scores to the scores from two published cohorts 1,2. The fertility treatment perception survey consists of two positive and four negative statements about fertility treatment with responses given on a five-point Likert scale (1= strongly disagree to 5= strongly agree). Responses are calculated by number of respondents with an agreement score of 4 and/or 5 divided by total number of respondents per sub-group; higher scores indicate stronger agreement. Analysis included summary statistics with means and standard deviations and independent student's T-test to compare the mean fertility knowledge scores.ResultsWe contacted 435 subjects; 91 respondents were enrolled (21% response rate). Respondents were 77% female [median age 33 years (IQR 23, 50)]. 51% completed high school or less and 18% used one or more DMTs, with 65% taking hydroxyurea. Table 1 shows the CFKS results. The average CFKS score was 50%, lower than the international cohort (50% vs. 57%, p<0.001) and higher than a cohort of Black women in Atlanta, GA (50% vs. 38%, p<0.001). Respondents with higher educational attainment had a higher score (55% secondary education vs. 44% primary education, p=0.04). The questions most answered correctly addressed the lack of correlation between erectile function and fertility (79%) and smoking's risk to fertility in men (69%) and women (71%). The questions least answered correctly were about classifying infertility (32%) and the impact of age effect (34%), overweight effect (25%), and sexually transmitted infections' effect on fertility (36%). There was no difference in knowledge scores by age, sex, or SCD treatment. Table 2 shows fertility treatment perception survey results. Some respondents (34%) agreed that fertility treatments are safe. Almost half (46%) agreed that fertility treatments are effective. Over 60% of respondents agreed that fertility treatments are scary and/or cause emotional problems, while 48% agreed that fertility treatments may have short-term physical effects. There was no difference in responses by sex, age, or SCD treatment.ConclusionIn this study, we identify that higher educational attainment in adults with SCD is associated with better fertility knowledge. All subjects had low knowledge of sexually transmitted infections, weight gain, and older age as infertility risks. Although there is concern that hydroxyurea may compromise fertility, its use was not associated with greater fertility knowledge in this study. Given concerns about fertility in the SCD community, we identify an opportunity to support patients concerned about fertility by contextualizing real or theorized SCD-specific fertility risks within a broader set of established fertility risks.

Reducing Hospital Use of Urban Sickle Cell Adults Using Multidisciplinary Adult Care and Instrumental Support

Background: Sickle cell disease (SCD) is documented to be a key driver of adult hospitalizations, high length of stay, and frequent ED utilization at urban hospitals. In FY16 the average length of stay (ALOS) for adult SCD inpatient encounters at Virginia Commonwealth University Medical Center, an urban tertiary care center containing an adult SCD center, was 6.7 days, compared with an expected ALOS of 4.2 days. The 30-day readmission rate for SCD was 33.7%. Therefore, in an effort to reduce acute care utilization and re-hospitalization for VCU SCD adults, substituting it with ambulatory care and a medical home, we conducted a pilot study.Methods: we implemented Multidisciplinary Adult Care and Instrumental Support (MAIS), a form of the patient-centered medical home, for 5 of the highest SCD adult utilizers, among approximately 500 adults with SCD. There was not a control group. We hired and trained special SCD community health workers, labelled Patient Navigators (PNs), as case managers. PNs coordinated care with adult sickle cell providers, who customized medical interventions according to patient characteristics and needs discovered by PNs. PNs also coordinated care with hospitalists, ED physicians, social workers, mental health providers, and community resources. Issues addressed by PNs included housing, severe mental health and cognitive impairment, educational barriers, transportation barriers, poor ADL skills, domestic violence & stalking, and lack of family support. Analysis used a before-after design.Results: Included very high utilizing patients were ages (21 to 29), 2 were male and 3 were female. Insurance coverages included Medicaid, Medicare, Anthem health keepers and Optima Health. All 5 patients had multiple issues contributing to their high utilization. The 5-patient pilot evaluation showed a 1-year savings of $333,839, a 35.01% improvement for these 5 patients, calculated using the CMS percent change methods (($558,482.71 - $859,368.10)/$859,356.10X100). Additionally, 30-day readmissions were reduced by 18.4%, ALOS was reduced by 1.2 days, and the number of SCD clinic appointments doubled. The table shows savings in discharges, readmissions, and LOS, as well as increases in ambulatory care, for these patients.Conclusions/Future work: We conclude, in an uncontrolled pilot, there were dramatic reductions in hospital costs, discharges, readmissions, and length of stay, as well as increases in ambulatory care, resulting from using MAIS. Our pilot adds support to a growing body of data suggesting that a substantial case management support structure as part of a patient-centered medical home can reduce the risk of repeated ED visits, hospitalization, and lengthy stay in adults with chronic disease. Future work should include more rigorous evaluations, including costs of the program, control group comparisons, and return on investment, and should test whether this approach may complement or may be used instead of other approaches to improve LOS, readmission rates, and cost of care in SCD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of the COVID19 Pandemic on Admissions and Emergency Department Visits of Adults with Sickle Cell Disease

Background: The most common complication of sickle cell disease (SCD) in adults is vaso-occlusive crisis that is characterized by severe pain. These events can often be managed at home with oral analgesics, but if the pain is not controlled or the patient develops other associated problems, they seek care in an emergency department (ED). In the ED, they receive initial treatment with pain medications and are assessed for other complications such as infection and acute chest syndrome. If an individual's pain is not controlled in a short period of time, the majority of these patients are admitted to the hospital for inpatient management or placed in an observation unit (OBs) for 6-47 hours. The COVID-19 pandemic affected the Greater Newark community starting in mid March with the majority of all inpatient admissions (Ads) being COVID related through the end of May. It has been observed both at our medical center and nationally that during this time period and even afterwards, the number of ED visits and Ads had significantly fallen. The reasons for this finding may include fear of contracting COVID infection at the hospital, regular telemedicine (TM) calls to facilitate outpatient management, and an increase in the number of prescriptions of home pain medications. The purpose of this analysis was to examine patterns of ED visits, Ads, outpatient visits, prescription renewals and nurse (RN) and social worker (MSW) calls in order to determine the impact of COVID-19 infection on the local SCD community.Methodology: A retrospective review was undertaken of billing data and the EMR of all patients with SCD treated at Newark Beth Israel Medical Center (a 450 bed community-based academic tertiary care medical center) between January 2020 and June 2020. Data collected included the number of and reason for ED and OBs, Ads, the number of TM and outpatient visits, and MSW and RN telephone contacts. All patients 18 years of age and older were included. Overall, 100 adults with SCD received care between January and June.Results: Peak hospital COVID Ads, ED and OBs for all patients (SCD and non-SCD) occurred during the weeks between March 25 and May 24, 2020 with a daily inpatient census over 200 between April 7 and 24. SCD Ads at peak COVID (April-May) were significantly lower at 26±2/month compared to 64±11/month pre-COVID (January-February) (p= 0.04). ED and OBs were unchanged. During the peak of COVID, 10/93 (11%) SCD Ads (1 death) were COVID related with 80/96 (86%) for uncomplicated pain crises. MSW and RN called all patients proactively to offer support at onset of COVID pandemic. During this same time period, the number of MSW telephone contacts increased from 138±37/month pre-COVID to 372±21/month during COVID (p=0.02). RN contacts with SCD patients were stable and mostly were for pain prescription renewals. TM was initiated in March 2020 and an increase in these visits correlated with a fall in face to face physician visits: 83.5±11/month pre-COVID to 39.5±8/month peak COVID (p= 0.04), and TM 0/month pre-COVID and 31±4/month peak COVID (0.01).Conclusion: The outbreak of COVID-19 in the community reduced the number of Ads for patients with SCD without an increase in ED and OBs visits. MD face-to-face encounters were reduced but outpatient care continued with the initiation of TM, regular RN contact with maintenance of pain medication prescriptions and a greater numbers of MSW calls for psychosocial support. Further investigation and understanding of the use of Ads for SCD care, and the reduction during COVID, may have implications for current SCD management.DisclosuresCohen:GBT: Speakers Bureau.

The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications

Sickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.

Inconsistent Emergency Department Care: The Hidden Cost for Patients With Sickle Cell Disease

Inconsistent Emergency Department Care: The Hidden Cost for Patients With Sickle Cell Disease

Emergency Department Utilization for Patients Living With Sickle Cell Disease: Psychosocial Predictors of Health Care Behaviors

Study objectiveIndividuals living with sickle cell disease (SCD) often require urgent care; however, some patients hesitate to present to the emergency department (ED), which may increase the risk of serious clinical complications. Our study aims to examine psychosocial, clinical, and demographic factors associated with delaying ED care.MethodsThis was a cross-sectional study of 267 adults with SCD from the national INSIGHTS Study. The binary outcome variable asked whether, in the past 12 months, participants had delayed going to an ED when they thought they needed care. Logistic regression was performed with clinical, demographic, and psychosocial measures.ResultsApproximately 67% of the participants reported delaying ED care. Individuals who delayed care were more likely to have reported higher stigma experiences (odds ratio [OR]=1.09; 95% confidence interval [CI] 1.03 to 1.16), more frequent pain episodes (OR=1.15; 95% CI 1.01 to 1.32), lower health care satisfaction (OR= 0.74; 95% CI 0.59 to 0.94), and more frequent ED visits (OR=6.07; 95% CI 1.18 to 31.19). Disease severity and demographics, including sex, age, and health insurance status, were not significantly associated with delay in care.ConclusionPsychosocial factors, including disease stigma and previous negative health care experiences, are associated with delay of ED care in this SCD cohort. There is a need to further investigate the influence of psychosocial factors on the health care–seeking behaviors of SCD patients, as well as the downstream consequences of these behaviors on morbidity and mortality. The resulting knowledge can contribute to efforts to improve health care experiences and patient-provider relationships in the SCD community.

A CRISPR Focus on Attitudes and Beliefs Toward Somatic Genome Editing From Stakeholders Within the Sickle Cell Disease Community

(Abstracted from Genetics Med 2019;21:1726–1734.

Engaging Individuals with Sickle Cell Disease in Patient-Centered Outcomes Research: A Community Health Ambassador Training Model.

Developing innovative strategies to engage patients as research partners is a priority in efforts to reduce health disparities in underserved communities. We describe the development and implementation of a training model to prepare Community Health Ambassadors (CHAs) to serve as liaisons to engage individuals with sickle cell disease (SCD) in patient-centered outcomes research. We trained CHAs on research guidelines, human subjects' protection, and SCD self-management. Community Health Ambassadors then employed community-level strategies to engage individuals with SCD and their families (N=432) residing in rural and urban communities throughout Tennessee. By engaging the SCD community, CHAs identified areas of burden for self-management and patientpreferred strategies to engage members of underserved minority groups in research. This community-based training model, which places CHAs as liaisons between researchers and the community, holds promise for scaling-up for replication and implementation in studies seeking to engage underserved populations with a chronic disease in health research.

A CRISPR focus on attitudes and beliefs toward somatic genome editing from stakeholders within the sickle cell disease community

PurposeGenome editing holds both tremendous therapeutic promise and significant potential risk. Sickle cell disease (SCD), the most commonly inherited blood disorder, is a frontline candidate for the clinical applications of this tool. However, there is limited knowledge of patient community values and concerns regarding this new technology. This study aims to investigate the perspectives of three key decision-makers (patients, parents, and physicians) toward participation in future CRISPR-mediated somatic genome editing clinical trials. MethodsWe utilized a mixed-methods approach, involving an educational video tool, two-part survey, and 15 moderated, audio-recorded focus groups, which were conducted in seven U.S. cities. ResultsStudy participants expressed hope that genome editing technology would rechart the course for SCD, but concerns related to involvement burden, uncertainty of clinical outcomes, and equity in access were identified. Major themes emerged from the focus groups: facilitators of, and barriers to, participation in future somatic genome editing clinical trials; information pertinent to the decision-making process; persons from whom participants would seek counsel before making a decision; and recommendations for the research community on meaningful engagement as clinical trials are designed and approved. ConclusionThe advent of genome editing has renewed hope for the SCD community, but caution tempers this optimism.

Development and Implementation of the Sickle Cell Disease Ontology

Background: Sickle cell disease (SCD) is the most common monogenic disease in humans with multiple phenotypic expressions that can manifest as both acute and chronic complications. Although described more than a century ago, challenges in comprehensive disease management and collaborative research on this disease are compounded by the complex molecular and clinical phenotypes of SCD, environmental and psychosocial factors, limited number of therapeutic options and ambiguous terminology. Methods: Sickle Cell Disease Ontology (SCDO) was a community driven integrative and universal knowledge representation system for SCD, providing a controlled vocabulary developed by multi- and interdisciplinary groups of experts in both SCD and ontology design. The initial concepts in the ontology were generated using existing biological databases and ontologies, literature-based text mining and SCD management guidelines and standards of care from both resources-rich and resources-poor countries. SCDO is built around the central concept 'Hemoglobinopathy', allowing inclusion of non-SCD haemoglobinopathies, such as thalassaemias, which may interfere with SCD phenotypic manifestations. Findings: SCDO is the first and most comprehensive standardized human- and machine-readable resource that unambiguously represents terminology and concepts about SCD for researchers, patients and clinicians. It constitutes a comprehensive knowledge management system, standardize terminology of various SCD related factors, that will promote interoperability of different research datasets. Interpretation: This collaboratively developed ontology will help advance research and improve SCD management, by providing a well-structured format by which disease knowledge can be compared, integrated and shared. This will facilitate seamless data sharing and collaborations including meta-analysis within the SCD community and support the development and curation of data-basing and clinical informatics in SCD. The ontology will continue to be developed by the SCD community using best practices and guidelines. Funding: The development of the SCDO is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number U24HL135600; National Institutes of Health Common Fund grants U24HG006941 (H3ABioNet) and U01HG009716, Wellcome Trust/AESA Ref: H3A/18/001 and 1U54HG009790-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Declaration of Interest: No conflict of interest is declared. Ethical Approval: No ethics committee approval was required as no patient data is used in this work.