Comprehensive Sickle Cell Center Research Articles

Impact of Neighborhood Disadvantage on Preventive and Acute Care Utilization in Sickle Cell Disease.

Individuals with sickle cell disease (SCD) experience significant healthcare disparities; however, there is little known on the impact of psychosocial stressors and neighborhood disadvantage on preventive and acute care utilization in this population. A retrospective data collection was performed for all patients cared for at a comprehensive pediatric sickle cell center in the Midwest who had also completed the Psychosocial Assessment Tool (PAT), a validated caregiver-reported measurement of family psychosocial risk, from September 2021 through December 2022. Patient age, payor, primary language, frequency of acute and missed preventive care visits, as well as Area Deprivation Index (ADI) and Childhood Opportunity Index (COI) scores were collected for 256 patients. The average state ADI was 6.3 (±2.9), and the majority of patients were in the Very Low or Low COI categories. Total PAT score (p=0.003), state ADI (p<0.001), and state COI (p<0.001) were all significantly correlated with missed SCD clinic visits, with increased odds of a missed visit with increasing neighborhood disadvantage (OR 1.22, p<0.001). The odds of acute care were also increased in those with higher family psychosocial risk (OR 1.76, p<0.011), though this was not seen with ADI or COI, suggesting an additional effect of family stressors and resilience on acute care utilization. This highlights the importance of regular, universal social and psychological risk screening, as well as inclusion of psychosocial team members in SCD programs to identify and readily address risk factors that impact child outcomes in a minoritized chronic disease population.

Real-world experience of patients with sickle cell disease treated with crizanlizumab.

In 2019, crizanlizumab was approved by the Food and Drug Administration (FDA) to reduce the rate of vaso-occlusive crisis in patients with sickle cell disease (SCD). We aimed to study the real-world effectiveness of crizanlizumab in our comprehensive sickle cell center. This was a retrospective cohort analysis of patients with SCD who received at least two consecutive doses of crizanlizumab. Clinically significant improvement was captured using the patient global impression of change scale (PGI-C). As of December 2022, there were 18 patients eligible for analysis with a median age of 30.5 years. Eight patients had the HbSS genotype, 7 HbSC, and 3 HbSB null genotype. Median duration of exposure to crizanlizumab was 53.6 weeks, and 16 (88.9%) patients received crizanlizumab for ≥26 weeks. Crizanlizumab was very well tolerated with no serious adverse events (grade ≥3) related to treatment. There was no significant difference in laboratory parameters. There was a remarkable improvement in patients' subjective response to crizanlizumab infusion. The median PGI-C score of our patients was 5, signifying moderately better with slight but noticeable changes. The morphine equivalent daily doses (MEDD) were lower after crizanlizumab infusion. MEDD prior to crizanlizumab was 90; after ≥2 consecutive crizanlizumab doses, it was 60. There was also a reduction in the hospital admissions, emergency, and urgent care visit for acute pain crisis in 6 (28%) patients. This study shows that crizanlizumab was associated with improvement in patients' response, both directly and indirectly related to the reduction of opioids used, which is consistent with results from the SUSTAIN trial.

Delayed Management of Sickle Cell Disease Vaso-Occlusive Episodes and the Impact on Prolonged Hospitalizations at a Single Academic Center

Introduction: Sickle Cell Disease (SCD) affects nearly 100,000 people in the United States (Centers for Disease Control and Prevention, 2023). Vaso-occlusive episode (VOE) is the most common reason for hospitalization in SCD. Many providers are unfamiliar with the pain management timing and dosages required to adequately treat these episodes (Jang et al., J Transl Med 2021). Nationally, areas with comprehensive sickle cell centers have shown decreased hospital utilization, fewer VOEs, and improved quality of life (Oyedeji et al. JAMA 2020). Even in areas without a comprehensive center, implementing individualized pain care plans for SCD has reduced admission rates of high-utilizing patients while not impacting their pain rating scores (Welch-Coltrane et al. Pain Medicine 2021). Our academic hospital, Oregon Health and Science University (OHSU), lacks a comprehensive SCD center and VOE treatment plans are not easily accessible for these patients. We conducted a retrospective analysis on a cohort of patients with SCD to investigate the factors influencing the length of emergency department (ED) and hospital stays for VOE. We aim to identify if implementing individualized pain plans via a standardized template within the electronic health record (EHR) for these patients will decrease hospital admission, length of stay and time to ED discharge. We also aim to integrate individualized pain plans into the EHR that would allow for direct exposure to the care team by creating plans that are easily accessible, reviewed, and routinely utilized for clinical decision-making. Methods: We performed a preliminary retrospective analysis of encounters (n=107) from 2008-2023 at OHSU, where the primary diagnosis was either a VOE or an equivalent diagnosis. Based on data demonstrating earlier maximum opioid doses leading to shortened hospital stays in frequent pain patients, we recorded the timing of the first opioid and morphine milliequivalents per hour in the first 24 hours (Payne et al. Pediatr Blood Cancer 2018). Additionally, we recorded the length of stay, admission rates, time to first IV fluid, and the type of IV fluid used. We performed a linear regression analysis on the collected data with the dependent variable as the length of stay across the independent variables of time to first opioid, time to first intravenous fluid, and morphine milliequivalents per hour during the first 24 hours after presentation. Results: Eighteen patients accounted for the 107 analyzed encounters. Thirteen patients (72%) had Hgb-SS disease, 2 (11%) had Hgb-SC disease, and 3 (17%) had Hgb-S-beta thalassemia. Sixty-two admissions (58%) were ED discharges, and 45 (42%) were ED to hospital admissions. The length of stay and time to the first opioid positively correlated with p=0.005 (Figure 1a). The length of stay and time to first intravenous fluid administration was also positively correlated with p=0.01. The length of stay and morphine milliequivalents per hour in the first 24 hours were negatively correlated with p&amp;lt;0.0001 (Figure 1b). Conclusions: Longer time to administration of opioids and intravenous fluids correlated with a longer length of stay in both the ED and the hospital. Additionally, lower morphine milliequivalents in the first 24 hours of presentation were associated with a prolonged hospital stay at our institution. We hypothesize that these three factors are secondary to delays in care and inappropriate initial treatment of VOE. To address these factors, we aim to implement standardized pain plans in the EHR of our institution. Implementation of individualized pain plans, particularly in the ED, has led to the earlier initiation of opioids (Della-Moretta et al. Ann Emerg Med 2020). We anticipate similar effectiveness for timely and appropriate fluid administration and adequate opioid dosing. We plan to continue retrospective analysis and compare this data to VOE encounters post-implementation. By implementing individualized plans that are integrated within the EHR and efficiently utilized by the care team, we hope to improve VOE management at our institution with decreased length of stay, less ED to hospital admissions, and improved patient satisfaction.

The Renal Protective Effect of Sickle Cell Disease-Modifying Drugs

Background Patients affected by sickle cell disease (SCD) often present with renal impairment due to the deleterious effects of polymerized red blood cells at the level of the nephron. The resulting glomerular damage leads to proteinuria as well as increased tubular secretion of creatinine, which in turn allows for the use of the urine protein:creatinine ratio (PCR) to monitor disease progression in SCD patients. Aim We aimed to evaluate the renal protective effect of various disease-modifying therapies via changes in urine PCR. Method This was a retrospective cohort study of patients with SCD (all genotyped, ≥16 years old) at UT Comprehensive Sickle Cell Center during the study period of 2019-2023. Demographics, clinical, and laboratory findings were collected and analyzed. Both the albumin:creatinine ratio (ACR) and PCR are comparable measures of kidney function. We measured PCR at our center due to test availability, and it also allowed the measurement of non-albumin urinary proteins that maybe important for prognosis. PCR was measured once or twice annually. Descriptive statistics are presented in percentages, medians, and interquartile ranges. Changes in urine PCR were calculated based on the difference in initial and recent urine PCR. A positive change means that there was improvement in the most recent urine PCR (i.e., measuring less than the initial urine PCR) or vice versa. An unpaired Student's t test was used to determine the level of significance in differences between initial and recent urine PCR for various disease-modifying drugs, with p &amp;lt;0.05 considered to be statistically significant. Data was analyzed using GraphPad Prism version 9.0.2. Results There was a total of 90 study participants eligible for analysis during the study period. Forty-three (47.8%) were male and 47 (52.2%) were female; the median age was 30 (IQR 24-35.3) years. The most common genotype was HbSS (81.1%), followed by HbSC (10%), and HbSB null (8.9%). Patient with sickle cell trait were excluded from this study. The majority of the patients (81.1%) received at least one treatment, and 24 (26.7%) were on combination therapy. Among the various SCD-modifying therapies, hydroxyurea was the most common therapy (64.4%) used, followed by voxelotor (13.3%), crizanlizumab (12.2%), and L-glutamine (11.1%). A detailed analysis is given in Table 1. The median initial urine PCR was 140 (IQR 90.0-242.5) mg/g. The median recent urine PCR of the study cohort was 135 mg/g (IQR 88.5-287.5), and the median change was 0 (IQR -45.0 to 43.5) mg/g. In stratifying by different disease-modifying drugs, the median change in urine PCR for hydroxyurea was -106.3 mg/g, L-glutamine 5.5 mg/g, voxelotor 19 mg/g, and crizanlizumab -22 mg/g. There was a statistically significant difference in the change in urine PCR for voxelotor and L-glutamine, compared with hydroxyurea (p=0.0361 and 0.0423, respectively) (Figure 1). Conclusion This is one of the first retrospective analyses to evaluate the renal protective effect of disease-modifying drugs at our comprehensive sickle cell center. The SCD-modifying therapies voxelotor and pharmaceutical-brand L-glutamine had the highest renal protective abilities and were associated with significant changes in urine PCR, compared with hydroxyurea. Larger studies are needed to corroborate these findings.

Experiences with Working: A Letter from Older Adults with Sickle Cell Disease

Introduction With medical advancements over the past decades, the life expectancy for people with sickle cell disease (SCD) is longer than ever before. As they age, people with SCD acquire both SCD-complications and age-related comorbidities that lead to premature functional impairment, requiring individuals to make complex decisions that affect their work and career ambitions. There is a gap in the literature on work experiences in older adults with SCD. The purpose of this study is to describe the work experiences of older adults with SCD. Methods We enrolled 19 older adults with SCD (age ≥ 50) from a comprehensive sickle cell center. We conducted semi-structured interviews by phone and in-person. Participants were asked open-ended questions about their experiences living with SCD and their single biggest problem faced with having SCD. Participants described obstacles faced when working and strategies to continue working as older adults living with SCD. Audio-recorded interviews were transcribed verbatim. Conventional content analysis was used to analyze the transcripts. Results The mean age of participants was 58 years (range 50-71) and 47% were women. Nearly half were externally employed (47%), 5% unemployed, 11% retired, 32% disabled, and 5% self-employed. Only 21% had a high school education or less, 37% completed some college, associates, or technical school, 26% had a bachelor's degree, and 16% had an advanced degree. For household income, 37% earned ≤ $30,000, 16% earned $30,001-$50,000, and 42% earned &amp;gt; $50,001. The majority were the head of their household (53%) and 21% reported living alone. Within the last 6 months, 32% were hospitalized and 26% missed at least a day of work due to a pain crisis. Most participants (53%) had HbSS genotype, 37% had HbSC, and 11% had HbSβ+-thalassemia. There were two major work-related themes that emerged from the interviews (Figure 1). Theme 1 was “ Obstacles faced when working ”, which centered around interferences with work. Participants discussed the physical limitations, SCD-related complications, lack of energy to perform job tasks, and pain crises that would interfere with their work schedule and sometimes keep them out of work for years. Participants described concerns about being forced to retire early or give up their business due to health-related issues. Many described challenges with work as the single-biggest problem they faced as an older adult with SCD. Participants also described obstacles related to a lack of understanding from their employers. They described getting sick and staying in the hospital for days at a time, then being expected to return to work immediately after discharge. One participant described sharing their disease diagnosis with an employer and being discriminated against working that kind of job. Theme 2 was “Strategies to continue working”, which centered around participants knowing their limits and modifying the type of work they did. Participants described learning to listen to their body when it has reached its limit, knowing when to back away and come back to job responsibilities, and knowing when to take breaks. Participants also described the importance of finding accommodating employers who were understanding of when they had to miss work. Some participants described how they had to learn new skills to do alternative, more flexible jobs that were not as physically taxing on their body, such as working from home, starting a business, or becoming a real estate agent. They especially emphasized the importance of being aware of how far they could go with certain jobs to avoid triggering pain crises. Participants also described going through periods of temporary disability or retirement, then getting a new job and slowly working their way up from part-time to full-time. Conclusion Older adults with SCD provided insight into the unique obstacles they faced while working and described work-related challenges as the single biggest problem they faced. Moreover, many described the strategies they developed over time and accommodations that allowed them to continue working or re-enter the workforce. Data provided from these experiences convey the dire need for policymakers and employers to support accommodations needed by adults with SCD to continue working. This information will help guide younger adults with SCD to better navigate the working world and achieve their ambitions as they advance in age.

A Randomized Clinical Trial Testing the Effect of Digital Behavioral Interventions on Pain and Mental Health Among Adults with Sickle Cell Disease

Background: Patients with sickle cell disease (SCD) suffer a significant disease burden that affects their psychosocial well-being. Digital cognitive-behavioral therapy (CBT) has been utilized in other patient populations and shown to have clinical benefits. Although evidence-based, non-pharmacological interventions for pain management are widely used in other populations, this is not well studied in SCD. There are currently no large-scale, adequately powered clinical trials that evaluate the effectiveness and dissemination potential of digital behavioral pain management interventions for adults with SCD. Objective: The primary goal was to compare the effectiveness of two mobile-phone-delivered programs: 1) digital CBT program tailored for adults with SCD (CBT); or 2) pain and SCD education (Education) for reducing pain symptoms. The secondary goal was to assess whether baseline depression symptoms moderated the effect of these interventions on pain outcomes. Methods: Cognitive Behavioral Therapy and Real-Time Pain Management Intervention for Sickle Cell via Mobile Application (CaRISMA) is a multisite, randomized, pragmatic, comparative effectiveness trial conducted at seven comprehensive sickle cell centers and several community-based organizations in the U.S. The study enrolled adults with SCD who reported chronic pain or using short or long-acting opioids daily. Participants were randomized in a 1:1 ratio to receive either the CBT or Education programs. Both programs utilized identical Facebook Messenger chatbot apps, only the content differed. All intervention participants received health coach support involving weekly phone calls or text messages for a duration of 12 weeks. Participants completed follow up assessments at 3 and 6 months, and daily e-diary entries of 0-10 pain numerical rating scale, mood, and opioid use. The primary outcome was the 6-month change in the PROMIS pain interference. Secondary outcomes included average daily pain intensity for a 2-week period at each time point, change in mean % body area affected by pain (measured by a ‘paintable’ body image within the mobile app), PHQ-9 depression, GAD-7 anxiety, Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) quality of life (social functioning and emotional impact), and Sickle Cell Self-Efficacy Scale (SCSES). Generalized linear mixed models were used to compare changes in 6-month outcomes between study arms after accounting for design variables (study site and baseline depression). Results: Of the 574 participants screened for eligibility, 359 (63%) were consented and randomized (178 to CBT and 181 to Education). Seventy-five percent of participants connected with the chatbot but only 47% completed at least one CBT/education lesson. However, 80% of participants had at least one text message, phone or video session with a health coach. At 6-months, there was a significant decline in pain interference within each arm (CBT [-2.13, 95%CI (-3.42, -0.84)] and Education [-2.66, 95%CI (-3.97, -1.36)]); however, this decline did not differ between arms (p=0.57). There was not a significant 6-month change in daily pain intensity for either arm, however, for % body area covered in pain, both CBT and education conferred a similar relative decrease, 19.2% and 17.1%, respectively. There were significant 6-month improvements within-arms for PHQ-9, GAD-7, and both ASCQ-Me measures, but no between-arm differences emerged. (Table 1). Of these, only the 6-month change in ASCQ-Me emotional impact approached a significant difference between arms with digital CBT conferring slightly greater improvement in scores, 3.51 (95%CI: 2.29, 4.73) compared to education,1.79 (95%CI: .55, 3.04; p=.05). Baseline PHQ depression score (&amp;gt;= 10 vs &amp;lt; 10) did not moderate the effect of treatments on pain interference (p=0.52). Conclusions: Preliminary trial findings suggest that both digital CBT and Education, with health coach support, are effective approaches for management of SCD pain and mental health symptoms. Most participants connected with a health coach and may have derived benefit from this support, however, poor engagement with the digital CBT and education component of the study may have limited the study's ability to detect between arm differences. Secondary analyses will examine the effect of intervention engagement on treatment outcomes.

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.

Sickle Cell Disease and Comorbid Psychiatric Conditions: A Single-Center Retrospective Study

Introduction: It is established that patients with various chronic disease states are predisposed to psychiatric comorbidities. However, in the sickle cell disease (SCD) patient population, psychiatric comorbidities have been uniquely shown to exacerbate disease through a psychosomatic component. A co-existing diagnosis of depression is found in 1 of 3 patients with SCD, and they are more than 5 times as likely to suffer from a mood disorder than the general population. SCD patients with psychiatric illnesses have significantly worse physical and mental health outcomes. Additionally, healthcare costs are more than double for SCD patients with depression than for those without. Thus, SCD patients with psychiatric comorbidities have unique challenges and are an important population to study. Methods: This was a retrospective single-center study of patients with SCD, all genotyped and ≥16 years old, who were treated at UT Physicians Comprehensive Sickle Cell Center during the study period (March-July 2023). The demographics, clinical characteristics, psychiatry history, initial and recent PHQ-9 results, and laboratory findings were collected and analyzed. Descriptive statistics were obtained and analyzed between SCD patients with and without psychiatric disorders and are presented in percentages, medians, and interquartile ranges. Data analysis was completed using a p value &amp;lt; 0.05 to indicate statistical significance, using an independent group unpaired t-test for continuous variables and Chi-square and Fisher's exact tests for categorical data, respectively. Data was analyzed using GraphPad Prism version 9.0.2. Results: Patient sex was 45% male and 55% female; 73% of patients had the HbSS genotype. Of the studied cohort, 33% were affected by at least one psychiatric disorder. The most common psychiatric disorder was depression, which occurred in 26% of patients, followed by anxiety (21%). The most common pharmacotherapy for psychiatric conditions was tricyclic antidepressants (TCAs), followed by SSRIs and SNRIs. There was no significant difference in ED visits or hospitalization rates between patients with known psychiatric disorders versus those without. Common laboratory markers used to assess SCD (LDH, total bilirubin, reticulocyte count) were overall higher in the subset with psychiatric illnesses, but only LDH was statistically significantly higher. Surprisingly, SCD patients with psychiatric disorders used fewer opioids than those without with a lower Morphine Equivalent Daily Dose (although this was not statistically significant). Conclusion: Although it is known that psychiatric illnesses in SCD patients are prevalent, exacerbate disease, and pose a cost burden, in our study there was nosignificant increase in hospitalizations or ED visits. However, it is notable that our study patient population was an outpatient population that is compliant and generally has access to resources including a robust behavioral health team and regular psychotherapy sessions. Due to these factors, ourdata may not be generalizable to the entire SCD patient population. Additionally, althoughlaboratorymarkers were overall poorer in the psychiatric population, they were not statistically significant, perhaps owing to the small sample size. Our study calls for a broader look at SCD patients with psychiatric illness, perhaps also to review these variables in SCD patients in the inpatient setting. A future direction could also be to evaluate the efficacy of psychiatric pharmacotherapy versus cognitive behavioral therapy in this patient population. Word count: 518 words

Acute Chest Syndrome at the Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System

Background: Individuals who have sickle cell disease (SCD) are susceptible to several severe consequences, such as vasoocclusive crisis (VOC), which may further develop into acute chest syndrome (ACS), a specific type of acute lung injury. Although VOC can result in substantial morbidity, it is important to note that ACS is the primary cause of mortality among individuals with SCD. Despite the devastating consequences of ACS, no interventions exist that directly treat this complication. Consequently, when patients present with ACS, their treatment options are frequently limited to supportive care. The absence of ideal therapeutic interventions for individuals with SCD who are experiencing ACS is a significant factor in their increased rates of illness and death. A cohort of adult patients diagnosed with ACS was examined with the objective to evaluate indicators of disease severity and identify risk factors associated with recurrent ACS. Methods: The Emory University Georgia Comprehensive Sickle Cell Center, located at Grady Health System, offers a dedicated acute care unit (ACU) that operates around the clock. This unit is specifically designed to assess and manage SCD patients who present with sickle cell crises. A pilot retrospective study was undertaken to analyze 25 patients with ACS. The evaluation included the examination of admission laboratory results, demographic information, past medical history, co-morbidity, interventions for each ACS admission for each patient (refer to Table 1). Descriptive statistics were used to report frequencies or median and range (Table 2). Patient characteristics of patients with 1 ACS event versus those with recurrent ACS (&amp;gt;=2) were compared using fishers exact test or the Wilcoxon-rank-sum test. Statistical significance was set at 0.05. Analysis was completed using SAS 9.4 (Cary, NC). Results: A total of 47 ACS episodes were detected in a cohort of 25 individuals, resulting in a median of 1 ACS event per patient (range of 1 to 6). A total of 85% of the patients included in this study had homozygosity for SCD, whereas 36% of the patients were receiving hydroxyurea treatment. Chronic pain was reported in three-fourth of the cohort. Out of all the ACS events observed, only 40% necessitated red cell exchange transfusion. A correlation between a minimum hemoglobin (Hb) level of 3.3 g/dL and lactate dehydrogenase (LDH) levels over 4000 U/L was noted during ACS admission. These findings indicate the presence of intravascular hemolysis. Three individuals died to ACS. Next, we conducted a comparison between a group of 10 patients who experienced recurring ACS events, with a minimum of 2 to a maximum of 6 occurrences, and another group of 15 patients who only had a single ACS episode. The group of patients with recurrent ACS exhibits a median of 5.5 episodes of VOC that necessitate visits to the acute care unit within the year prior. In contrast, the group with a single ACS episode has a median of 1 event. There was a notable disparity in the frequency of transfusions received by patients with recurrent ACS compared to those who experienced only a single episode over the past year. Although no other variable demonstrated statistical significance, the recurrent ACS group exhibited lower levels of hemoglobin and higher levels of LDH in comparison to the group with a single ACS episode. Further examination of our patients with SCD could provide valuable insights into the potential factors that may predict ACS episodes. These factors include a patient's genetic background, the frequency of VOC, the use of hydroxyurea, evidence of hemolysis, and previous blood transfusions. Furthermore, the utilization of acute care unit by patients with SCD has had a positive effect in our cohort, on the reduction of red cell exchange transfusions and mortality rates from ACS, possibly from early identification and episodic transfusion, in comparison to similar cohorts with ACS.

Sickle Cell Disease Electronic Health Record Population Management Approach to Support Delivery of High-Quality Care: Leaving Paper Lists behind

Children and young adults with sickle cell disease (SCD) require complex health care services to screen for early signs of disease-related complications and to initiate and monitor disease-modifying therapies. Care coordination is challenging as it involves multiple team members across multiple subspecialties. Evidence-based clinical protocols and quality metrics are essential for SCD programs to deliver high-quality care. Systems to track this care delivery are crucial to ensure equitable, accessible care is consistently provided. In 2016, the Comprehensive Sickle Cell Center (CSCC) and the Population Health Innovation Team at Children's Hospital of Philadelphia (CHOP) developed and implemented an electronic health record (EHR)-based system, the SCD patient registry and proactive care outreach tools, to facilitate processes needed to ensure patient service delivery in a timely fashion. We selected Transcranial Doppler (TCD) ultrasounds, hydroxyurea therapy initiation, and annual clinic visits to monitor stroke risk screening, disease-modification therapy, and general chronic illness care. Between January 2015 and June 2023, approximately 1400 patients with SCD were tracked across two CHOP outpatient clinics, the CHOP Philadelphia and CHOP Voorhees campuses. We tracked TCD completion, hydroxyurea prescriptions, and clinic visits per year for age-eligible patients with SS and SB0thal. Prior to implementation of the EHR-based tools and new workflows in October 2016, for age-eligible patients, on average 75% of patients had received annual TCD screening, 55% of patients had received hydroxyurea prescriptions within the prior 6 months, and 85% had attended outpatient hematology clinic at least twice within the year. As of June 2023, on average, completed TCD visits had increased to 91%, patients prescribed hydroxyurea had increased to 78%, and patients attending 2 clinic visits within a year had increased to 89%. These metrics remained consistent and improvement was sustained despite the COVID-19 pandemic. Table 1 describes the drivers influencing these improvements, which included various interventions involving social work, nursing, community health workers, registrars, care coordinators, and physicians. Figure 1 illustrates the changes achieved over time in rates of TCD completion, hydroxyurea prescriptions, and clinic visit attendance. This implementation of an SCD EHR-based population health tool and new care team workflows facilitated more efficient processes for various care team members and improved our ability to consistently provide timely services to children and young adults with SCD. This resulted in sustained improvement in all metrics and high-quality care for our patients.

Experiences with Delayed Diagnosis for Older Adults with SCD: “Looking Back It All Makes Sense”

Background Improvements in care over the last 50 years have extended the median lifespan of people living with sickle cell disease (SCD) from 14 years to as long as 61 years in cohorts from academic centers. Older adults with SCD have decades of unique experiences; from navigating their initial SCD diagnosis to coping with complications of SCD as an older adult. The purpose of this study was to describe the impact of delayed diagnosis of SCD on older adults (age ≥ 50 years). Methods We enrolled 19 older adults with SCD from a single comprehensive sickle cell center. We conducted semi-structured interviews by phone or in person. A single interviewer asked open-ended questions about the participant's experiences living with SCD during childhood and adulthood. Participants described their experiences being diagnosed with SCD, how they navigated healthcare systems, and their strategies to manage and prevent pain crises. Interviews were audio-recorded and transcribed verbatim. We used conventional content analysis to code the transcripts. Results The mean age of participants was 58 years (range 50-71). Over half (53%) had HbSS genotype, 37% had HbSC, and 11% had HbSβ+-thalassemia. Almost half (45%) were hospitalized and 63% had an emergency room visit in the last year. Most participants (84%) were on short-acting and 37% were on long-acting opiates. The majority (58%) reported current use of hydroxyurea. In theme 1, many participants described growing up with an unknown illness prior to their SCD diagnosis. Participants discussed having pain episodes but not knowing they had SCD. Their symptoms were often dismissed as “growing pains” or “bone pain”. Participants stated how not having a diagnosis as a child was hard on their parents and they had to see various specialists or travel to academic centers to finally receive a diagnosis. Participants shared stories about how they were diagnosed with SCD (Figure 1). Participants discussed positive aspects of not knowing they had SCD. They described how their parents allowed them to do activities and pursue ambitions without limitations since they were unaware they had a life-limiting condition. In theme 2, participants described the impact of having providers with limited knowledge about SCD. They described challenges having limited access to treatments for pain before and after their diagnosis of SCD. They discussed how doctors were not as empathetic in the past as they are now. Doctors were more likely to stigmatize them as being “drug-seekers”. Some participants stated they still felt “hurt” by how they were stigmatized and remain “very afraid” to seek care in their local hospitals for fear the providers were not knowledgeable about SCD. They recalled difficulties accessing pain medications as children and young adults due to providers' reluctance to treat them. These challenges led them to develop alternative coping strategies aside from opioid medications. Many older adults used therapies such as warm compresses, heating pads, prayer, meditation, healthy eating, proper hydration, and avoiding factors like overexertion and weather extremes. Later in life, these older adults also were more inclined to seek out alternative therapies such as acupuncture, physical therapy, aquatic therapy, and biofeedback to manage their pain. Conclusion Older adults in this study lived for many years not knowing the cause of their symptoms and how best to treat their illness. While delayed diagnosis of SCD is now rare in countries with universal newborn screening, there remains many undiagnosed people with SCD around the world. This delayed diagnosis leads to unnecessary pain and suffering for patients and their families. Participants expressed their frustration with the medical community for their lack of knowledge as to the source of their pain, their dismissive nature of said pain, and their undertreatment of these symptoms. This study highlighted the need for providers to really listen to patients and their families and take their symptoms seriously. There is much to be learned from older adults about self-management of SCD and much work to be done to repair relationships that have been broken due to mistreatment of this population by healthcare providers. In ongoing studies, we partner with older adults with SCD to increase knowledge and develop management strategies, similar to those used in geriatrics, to improve care for older adults with SCD.

COVID-19 Outcomes at a Comprehensive Sickle Cell Center: A Two-Year Report

The Georgia Comprehensive Sickle Cell (SC) center at Grady health system is the largest adult comprehensive sickle cell center in the United States and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). in 2019, the center provided around 3000 sickle cell clinic visits and 4000 acute care visits. When the COVID-19 pandemic reached the US, the SC center had seen a precipitous drop in the number of both clinic and acute care visits as local and state regulations for lockdown were passed. On the two-year anniversary for the COVID-19 pandemic, we are submitting this report of all the COVID-19 cases at a single adult center for sickle cell disease. Since the start of the pandemic, we have been tracking any COVID-19 cases reported in the patient population the SC center follows. Out of 1343 patients currently following in the center, 173 patients contracted COVID-19 between March 2020 and February 2022, and were tracked in the clinical database under IRB approval. The results show that of the 173 patients, 85 were female and 89 were male. By genotype, 62% of patients were SS, 29% were SC and 9% were Sβ+ thalassemia or Sβ0 thalassemia. 32% of patients were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 45% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain was defined in the patients experiencing daily pain episodes for more than 4 days a week for the last 3 months and calculation of daily morphine equivalents was reported based on the clinic follow-ups and the narcotic database utilization. 35% of the SC patients had chronic pain and the median morphine equivalents was 90 mg daily with a range between 45 and 225mg. On evaluating the rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19, 85% of patients had either an ED visit or hospitalization. 54% of the SC patients had the reason for the visit related to VOE and 29% had the reason related to COVID-19 primarily. 15% of SC patients were not seen in any emergency setting or required any hospitalization. 22% of the patients had lung findings on imaging. The treatment utilized for the patients was most commonly Remdesivir in 33, dexamethasone in 26, red cell products in 21 and monoclonal antibody in 13 patients. Of the 3 deaths reported, 2 happened early in the pandemic. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure (MOF) for which a red cell erythrocytapheresis was attempted to no avail. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma to no avail after development of MOF and ARDS. The third death occurred in August 2021 during the delta variant wave and the patient was hospitalized for COVID-19 pneumonia and had initial improvement after initial treatment but after worsened lung findings, ARDS developed followed by MOF. Several reports from different centers have been published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 63 out of 173 (36%) patients who had contracted COVID-19 required treatment and 3 of those 63 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 respectively and since then, the rate of complicated COVID-19 hospitalizations has decreased with better treatment available. No deaths were registered during the omicron wave and 1 death was registered during the delta wave. In addition, the timeline for the COVID-19 cases reported fits the population timeline of peaks respectively happening in the summer of 2020, winter of 2021, summer of 2021 and winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the SC center resorted to virtual visits utilization to deliver the needed healthcare visits to the patients. This measure has aided in protecting patients against COVID-19 during the multiple COVID-19 peaks occurring in the last 2 years and has accordingly reduced the mortality and morbidity of the patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Experience of Patients with Sickle Cell Disease Treated with Crizanlizumab: A Single Comprehensive Sickle Cell Center Retrospective Cohort Analysis

Background:Sickle cell disease (SCD) is an inheritable hemoglobinopathy with great impact on patients’ quality of life and healthcare costs. In 2019, crizanlizumab, the first-in-class monoclonal antibody that target the cell adhesion molecule P-selectin, was approved by the FDA to reduce the rate of vaso-occlusive crisis in patients with SCD ≥16 years old, based on the results of the SUSTAIN trial [1]. Aim: To study the real-world effectiveness of crizanlizumab in patients with SCD ≥16 years old treated with crizanlizumab 5.0 mg/kg, with or without hydroxyurea, from 2019 to 2022 in our comprehensive sickle cell center. Methods: This is a retrospective cohort analysis of patients with SCD (all genotyped, ≥16 years old) who received at least 2 consecutive doses of crizanlizumab. Demographics and laboratory findings before and after crizanlizumab were collected and analyzed. Only data available from patients’ electronic medical records (and other secondary data sources) 1 year before (pre-index data) and after (post-index data) the ≥2 consecutive crizanlizumab doses were analyzed. Objective clinical improvement was captured using the Patients’ Global Impression of Change (PGIC) score. Descriptive statistics are presented in percentages, medians, and interquartile ranges. An independent group unpaired Student's t-test was used to determine, where appropriate, the level of significant differences among normal distribution continuous variable with p value <0.05 considered statistically significant. Data was analyzed using GraphPad Prism version 9.0.2. Results:As of July 2022, there were 18 patients eligible for analysis. The median age of patients was 30.5 (range, 19-47) years, 7 (38%) males and 11 (61%) females (Table 1). Eight patients had the HbSS genotype, 7 HbSC, and 3 HbSB null. The median duration of exposure to crizanlizumab was 53.6 weeks, and 16 (89%) patients received crizanlizumab for ≥26 weeks. Crizanlizumab is very well tolerated with no serious adverse events (grade ≥3) related to treatment reported. The most commonly reported adverse events were fatigue (n=3), followed by headache (n=2) and nausea (n=2). There was no significant difference in laboratory parameters (hemoglobin, hematocrit, total bilirubin, creatinine, or protein/creatinine ratio) between pre-index and post-index values (Table 2). Although there was improvement in reticulocytes (6.5% vs. 5.1%) and LDH (336.5 vs. 279 U/L) compared with baseline, this was not statistically significant, likely due to the small sample size (p=0.71 and p=0.98, respectively). There was a remarkable improvement in patients’ subjective response with crizanlizumab infusion. The median PGIC score of our patients was 5, signifying moderately better with noticeable changes, although slight. Twelve (67%) patients provided a score of ≥4, which signifies feeling better with changes. Conclusions: This is one of the first retrospective studies to use PGIC to capture the effectiveness of crizanlizumab in patients with SCD. This study shows that crizanlizumab was associated with an improvement in patient response that was directly and indirectly related to the reduction of vaso-occlusive crisis, consistent with findings from the SUSTAIN trial. Further large-scale studies are needed to corroborate these findings.

Prevention and Management of Sickle Cell Pain Crises: Lessons Learned from Older Adults with Sickle Cell Disease

Background Innovations in medicine over the last fifty years have extended the median lifespan of people living with sickle cell disease (SCD) from 14 years to as long as 61 years in cohorts from academic centers. There is a paucity of information on the experiences preventing and managing vaso-occlusive pain crises by older adults with SCD. Older adults with SCD have decades of experience navigating pain and other complications of SCD. They have a wealth of knowledge about how to care for themselves, which can be shared with a younger generation of those with SCD. The purpose of this study was to describe strategies used by older adults (≥50 years) to prevent and manage pain crises. Methods We enrolled 19 men and women at least 50 years old from a single comprehensive sickle cell center in the Southeastern United States. We conducted semi-structured qualitative interviews by phone or in person. A single interviewer asked open-ended questions about the participant's experiences living with SCD and strategies they feel helped them live a long life. Participants described strategies they have adopted to cope with and prevent pain crises. A commercial service transcribed audio-recordings of the interviews verbatim. We used conventional content analysis to code the transcripts. Results The mean age of participants was 58 years (range 50-71). Over half (53%) had HbSS genotype, 37% had HbSC, and 11% had HbSβ+-thalassemia. Almost half (45%) were hospitalized and 63% had an emergency room visit in the last year. Most participants (84%) were on short-acting and 37% were on long-acting opiates. The majority (58%) reported current use of hydroxyurea. During the interview participants discussed strategies used to prevent and manage their pain crises. There were two major themes. (Figure 1) Theme 1 was "Strategies for Pain Prevention", which centered on methods they adopted throughout their lives to help prevent pain crises. Participants described that when they were younger pain medicine was not readily available, causing them to focus on strategies to prevent pain crises. They often relied on their parents to set limits on their activity levels to avoid having a crisis. When they reached adulthood, they learned to advocate for themselves by communicating their limitations. Having a good support system to encourage them to rest also helped. Most participants emphasized the importance of moving at their own pace and slowing down when they needed to. They discussed how knowing their triggers helped avoid a pain crisis or manage it better on their own. Sometimes simply sleeping once they felt a pain crisis coming on could help avert a crisis. Avoiding stressful situations, emotional triggers, temperature extremes, being underdressed, sitting long periods, and dehydration helped to prevent pain crises. Most participants described how a healthy diet and exercise were key in the prevention of pain crises. Eating fruits and vegetables, avoiding sugary drinks, excessive alcohol, and processed foods helped reduce pain episodes. They described low impact exercises they engaged in such as walking, yard work, and cycling. Theme 2 was "Strategies for Managing Pain” which included using pharmacological and non-pharmacological methods. One of the most important strategies participants mentioned was to rest as soon as a pain crisis started. For some, physical activity helped relieve pain, while for others, it was a trigger for a crisis. The strategies adopted also included hydration, heating pads, resting, distraction techniques, and avoiding stress as much as possible. Alternative pain management strategies that were reported included acupuncture, massage, and aquatic therapy. While pain medication was useful, many participants stated that they did not like being prescribed pain medicine without other therapies. Conclusion The growing population of older adults with SCD have a wealth of knowledge that can benefit younger adults with SCD to prevent and manage pain crises. Strategies they have learned through a lifetime of experience living with SCD have given them a unique insight into how to best cope with pain crises. In future research we will evaluate how best to share approaches developed by people with SCD for preventing and managing SCD complications. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Vaccine Schedule Disparities Exist for Pediatric Patients with Sickle Cell Disease

Background: Sickle cell centers and pediatricians often work together to ensure appropriate vaccination of patients with sickle cell disease (SCD). Patients with SCD are at high risk for serious infections with encapsulated bacteria, such as Neisseria menigitidis and Streptococcus pneumoniae; thus, vaccine recommendations for pediatric patients with SCD differ from those for the general population. The University of Alabama at Birmingham Lifespan Comprehensive Sickle Cell Center (UAB) encompasses four care locations: the academic center in Birmingham and three satellite clinics (Montgomery, Opelika, Tuscaloosa). Unlike the academic center where providers are reliant on pediatricians to ensure adherence to recommended vaccines (with the exception of PPSV23), patients seen in the satellite clinics are provided with a prescription for PPSV23 and instructed to obtain it through their pediatrician. Data from prior studies suggest that pediatric patients with SCD may have lower vaccination rates than the general population. Thus, the purpose of this study was to determine adherence to recommended SCD-specific vaccination schedules among pediatric patients cared for at UAB , by: 1) determining the mean age at initiation of the HPV, MenACWY, Men B, and PPSV23 vaccines among UAB pediatric patients, compared with SCD-specific recommendations for initiation of each of these vaccines; and 2) comparing vaccination rates for HPV, MenACWY, and Men B among UAB pediatric patients age 13-17 years vs. general population peers. Methods: We performed a retrospective chart review of clinic notes and the Alabama state vaccine registry (Immunization Patient Registry with Integrated Technology [ImmPRINT]) for records of UAB patients, to determine the age at vaccine initiation and number of doses received for HPV, MenACWY, Men B, and PPSV23 vaccines for all 870 UAB patients aged 3-22 years. We calculated the mean age at which the UAB patients initiated each vaccine, the proportion of patients completing each vaccine series, and (for PPSV23) whether patients were vaccinated at UAB or at another location. We used CDC published vaccination rates for HPV, MenACWY, and MenB from 13-17-year-olds in the general population (Pingali et al., MMWR Morb Wkly Rep 2021) to compare with rates from UAB patient peers. Results: The 870 UAB patients were an average age of 12.1 ± 5.4 years; 51.5% were male and 33.9% received most of their care at satellite clinics. HPV vaccination: Mean ±SD age at HPV vaccine initiation was 11.3±1.2 years (recommended age at first dose=11 years, there are no SCD-specific guidelines for HPV vaccination); coverage for HPV vaccine series initiation and completion among 13-17-year-old UAB patients vs. general population peers was 77.8% vs. 75.1% and 58.2% vs. 58.6%, respectively (Table). Meningococcal [MenACWY] vaccination: Mean±SD age at MenACWY initiation was 11.2±1.8 years (recommended age for patients with SCD is 2 months (MenACWY Menveo) or 24 months (MenACWY Menactra); recommended age for general population is 11 years). We found that patients with SCD were 32 (95% confidence interval [CI]: 22-47) times more likely to receive MenACWY after age 11 years. Meningococcal B [MenB] vaccination: Mean age at MenB initiation was 13.5±2.3 years (recommended age for SCD patients is 10 years; vaccine is optional for general population); coverage for ≥1 MenB dose among 13-17-year-old UAB patients vs. general population peers was 17.5% vs. 28.4%, respectively. PPSV23 vaccination: Overall PPSV23 coverage for UAB patients was 70.6%; patients seen at the academic medical center were 1.5 (95%CI, 1.1-2.0) times more likely to receive PPSV23 than patients seen at a satellite clinic (75.2% vs. 59.6%, respectively). Conclusion: Adherence to SCD-specific vaccination age recommendations is poor. We found that patients with SCD were more likely to receive vaccines according to the general population vaccine schedule rather than the SCD-specific vaccine schedule. In addition, reliance on pediatricians to provide PPSV23 for satellite clinic patients resulted in lower PPSV23 vaccination rates among these patients. These data suggest a disparity in adherence to SCD-specific vaccination schedules and suggest the need to develop and test a healthcare provider-focused intervention aimed at improving adherence to the SCD-specific vaccination schedule for children with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Incomplete Surveys on Data Analysis of Sexual Health Concerns in Adults with Sickle Cell Disease

Introduction: Studies focusing on sexual health in relation to sickle cell disease are rare, with a PubMed search producing only 70 results, and research in this area focusing specifically on incomplete data is severely limited. The objective of this analysis is to uncover differences between completed surveys and incomplete surveys among adult survey participants with sickle cell disease to reveal a more comprehensive picture of the sexual health concerns of patients with sickle cell disease. Methods: A study targeting sexual health concerns among adults aged 18 years old and older with a sickle cell disease diagnosis was conducted between August 2019 and August 2020 at Duke's Adult Comprehensive Sickle Cell Center. Survey questions consisted of demographic questions as well as categories of sexual health concerns for both male and female participants. Study participation was not compensated and was completely voluntary. Patients were approached and consented by clinic staff following appointment check-in. Surveys were then aggregated into an Excel sheet and underwent data analysis. Incomplete surveys were sorted out on the basis of one or more incomplete questions and/or demographic responses. Incomplete and complete surveys were further analyzed in Microsoft Excel. Results: The demographic breakdown of completed surveys and incomplete surveys showed significant differences. Completed surveys consisted of 48% (N=48) female and 52% (N=51) male responses. Incomplete surveys consisted of more female responses with a 59% (N=32) female and 41% (N=22) male. Chiefly, the analysis of incomplete surveys revealed that male participants were more concerned about relationship changes with an intimate partner than female participants, with 9% of males and 6% of females reporting this concern. This presents a contrast to the completed survey group in which 6% of males and 8% percent of females were concerned about relationship changes with an intimate partner. Though female respondents had more incomplete surveys, male respondents expressed fewer concerns as compared to the completed surveys group. A full analysis of incomplete surveys revealed that the concerns of scrotal tenderness, penile tenderness, pain and discomfort with masturbation, pelvic pain, and difficulty achieving a comfortable position for intercourse were completely missing from male respondents with incomplete surveys. However, these same categories had a reporting percent in the completed surveys category among male respondents, with each category having 2% to 10% of male respondents reporting it as a concern. For female respondents, only one category, pain or discomfort with masturbation was absent from the analysis of incomplete surveys and had a 2% reporting rate among completed surveys. Conclusion: Overall, our results show that there are discrepancies in survey results that may disproportionately affect the measurement of sexual health concerns among adults with sickle-cell disease. Female participants were shown to comprise 59% percent of incomplete surveys versus 48% percent of complete surveys, indicating that there is an area of improvement to encourage more female responses. Additionally, male participants with incomplete surveys had many more concerns unreported, indicating there may be discomfort with addressing these concerns. Cliniciansshould be encouraged to takethe opportunity to allow more open discussions of such topics with male patients. In conclusion, incomplete surveys offer additional insight into the pressing issues of the sexual health concerns of adult patients with sickle cell disease that may be under-reported otherwise in this understudied demographic. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19 Infection and Outcomes at a Comprehensive Sickle Cell Center

Introduction: The Grady Comprehensive Sickle Cell (SC) center is the largest adult sickle cell center in the United States (US) and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). In 2019, the center provided 3077 sickle cell outpatient visits and 3695 acute care visits. When the COVID-19 pandemic reached the US, the center had a precipitous drop in the number of both outpatient clinic and acute care visits as state regulations for lockdown were passed. This report follows all the COVID-19 cases at a single adult center for sickle cell disease in one year.Methods: The clinical database has been tracking COVID-19 cases reported. Out of a total of 1343 patients, 55 patients contracted COVID-19 and were tracked in the clinical database with IRB approval.Results: Of the 55 patients with COVID-19, 28 were female and 27 were male. By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ+ thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain (defined as patients experiencing daily pain episodes for more than 4 days a week for the last 3 months) and calculation of daily morphine equivalents were reported in clinic follow-up and the narcotic database utilization. 47% of the patients had chronic pain and the median morphine equivalents was 90 mg daily (45-225mg).The rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19 was 80%. 49% of the SC patients' visits were related to VOE and 27% related to COVID-19 primarily. 20% of SC patients with COVID-19 were not seen in any emergency setting or required any hospitalization.The COVID-19 signs and symptoms experienced by the patients were as follows: 58% had pain as the main presenting symptom, followed by cough and fever (40%), dyspnea (31%), and pneumonia with chest x-ray evidence (25%). 2 patients developed acute respiratory distress syndrome (ARDS) and were intubated, and 2 patients died. 29% of the patients had lung findings on imaging and 16 of 55 patients required treatment with the use of Remdesivir in 9, dexamethasone in 8 and red cell products in 7 of the 16 patients. The 2 patients who died had both presented with COVID-19 infection in June and July 2020 respectively. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure for which a red cell erythrocytapheresis was attempted. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma with development of multi-organ failure and ARDS.Discussion:Several reports were published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 16 out of 55 patients who had contracted COVID-19 required treatment and 2 of those 16 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 when 20 total cases were diagnosed (from March to Septemeber 2020). The remaining 35 cases registered zero deaths (October 2020 to March 2021) with the rate of complicated COVID-19 hospitalizations decreasing with better treatment available. In addition, the timeline for the COVID-19 cases reported fits the population timeline of 2 peaks respectively happening in the summer of 2020 and the Winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the center adopted virtual visits to deliver healthcare needs. This measure has aided in protecting patients against COVID-19. Additionally, it is interesting that despite the second peak in the winter of 2021, there were no reported deaths among the patients who developed COVID-19. This finding can suggest that despite the concern for morbidity and mortality of sickle cell patients, their diligence and awareness to stay home during the pandemic has proven crucial in reducing morbidity and mortality and the option of virtual visits for healthcare delivery was key and should be utilized further in sickle cell care. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Incidence of Stroke and Other Brain Imaging Findings in Adult Patients with Sickle Cell Disease: A Retrospective Study

Background: Vaso-occlusion and hemolytic anemia are the main features of sickle cell disease. Central Nervous system complications of sickle cell disease (SCD) can include silent cerebral infarcts (SCI), hemorrhagic or ischemic strokes, seizures and Moyamoya syndrome. SCI is the most common neurological complications in SCD. SCI patients have abnormal Magnetic Resonance Imaging (MRI) of the brain with normal neurological examination and no history of stroke. More precisely, Casella et al in the Silent Cerebral Infarct Multi-Center Clinical trial (SIT) defined infarct as MRI signal abnormality that was at least 3 mm in one dimension and that was visible in two planes on fluid-attenuated inversion recovery T2 -weighted images, as determined by agreement of two of the three study neuroradiologists. SCI in children is associated with lower Intelligence Quotient and increased risk of stroke.Methods: In this retrospective study we reviewed 100 adult patients at our Comprehensive Sickle Cell Center. We looked at the incidence of documented stroke and other neurological complications in SCD patients. We reviewed the hospital records of SCD patients for any incidental brain imaging (MRI brain or Computed Tomography(CT) brain) findings, done as inpatient or in the emergency room as part of hospital visits.Results: Out of the 100 patients, 14 patients had documented stroke. On the review of other 86 patients, 10 patients had MRI brain, 23 patients had CT brain, and 53 patients had no brain imaging record. Out of the 10 patients with MRI brain, 7 patient had significant findings- 3 patients had small vessel ischemic changes, 1 patient with chronic petechial hemorrhage of cerebellar vermis, 1 patient with ischemic changes and Chiari malformation type 1 (CTM 1), 1 patient with CTM 1 and non-specific white matter changes and 1 patient with CTM 1 alone. Out of the 22 CT of the brain and 1 CT angiogram of brain, 2 imaging showed ischemic changes and the angiogram showed large cerebral vessel narrowing. Therefore, on our review, 19 patients out of 100 were found to have stroke and 24 out of 100 had significant neurological findings. However, only 14 out of 19 patients had documented stroke. 7 out the 10 patients with MRI brain had significant incidental neurological findings. The number of adult SCD patients with neurological findings in our cohort could have been higher, if we had brain imaging record for the 53 other patients.Conclusion: This study shows that there is a heavy burden of neurological complications in SCD patients and SCI is under-diagnosed. MRI brain is superior to CT brain in detecting neurological complications in SCD patients. SIT showed that regular blood-transfusion significantly reduced the recurrence of cerebral infarct in children with SCI. Finding of SCI in adults also warrants consideration for follow up brain imaging, neurology referral and discussion of treatment modalities including chronic blood transfusion and hydroxyurea therapy. CTM 1 can also be associated with SCD. In CTM 1, tonsil herniates 5 millimeter or below foramen magnum. SCD may cause increased thickness of calvarium from extramedullary hematopoiesis in skull, which can result in cranio-cephalic disproportion with cerebellar ectopia and subsequent CTM 1. Because of high incidence of neurological complications in SCD patients, routine screening with MRI brain should be considered in adult SCD patients. DisclosuresIdowu: Forma Therapeutics, Inc.: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ironwood: Research Funding.

The Mortality of Adult Sickle Cell Patients at a Comprehensive Sickle Cell Center

Sickle cell disease (SCD) is the most common hemoglobinopathy affecting 100,000 people in the United States. Although without a national registry, the precise number remains an estimate and the mortality data remains unknown. The life expectancy of SCD has extended into adulthood with the advent of prophylactic penicillin use, antipneumococcal vaccines, newborn screenings, and use of hydroxyurea (HU). However as SCD patients age, comorbidities arise reducing the life expectancy.There is an evolving landscape regarding SCD therapies, with 3 FDA approved drugs since 2017 (L-glutamine, voxelotor, crizanlizumab) joining HU which was approved in 1998. It is paramount to understand the factors that lead to early mortality in SCD so that future therapies and cures can be accessible and benefit all SCD patients. We embarked a review of the mortality data in a healthcare system serving a significant number of SCD patients in Atlanta, GA.Methods:We conducted a retrospective chart review of the Georgia Comprehensive Sickle Cell Center at Grady Health system's electronic medical record for deceased sickle cell patients from 2013 to 2020. Patients were then grouped into 3 groups, those whom followed up at the Sickle Cell Center (defined as outpatient visit within 6 months prior to death-RF), those whom did not (defined as outpatient visit > 6 months-NF), and those with unknown status.Results:Overall, 72 patients were analyzed, with the following genotype distribution: SS n=49, SC n=14, Sbeta null thalassemia (Sβ0 thal) n=2, SBeta plus thalassemia (Sβ+ thal) n=7. Overall, the most common SCD complication was acute chest syndrome (ACS) (62.5%). The majority had hypertension (HTN) (52.8%), followed by reported heart failure (40.3%) and pulmonary HTN (pHTN) (40.3%), stroke (37.5%), and chronic kidney disease (CKD) (31.9%). 35% were current and/or former smokers. Median TR max velocity was 2.8 m/sec, median albumin/Cr ratio was 27.8 mg/g, and other characteristics are in Table 1.The median age of death was 44 (STD= 15.5) overall and by genotype it was: SS at age 38 (STD=14.6); Sβ0 thal at age 42.5 ( STD=2.12); Sβ+ thal at age 50 ( STD=14.7); SC at age 51 (STD=16.5). 46 patients had data of their final hospitalization available. 73.9% (n=34) received at least 1 simple transfusion with a only 17.4% (n=8) receiving an exchange transfusion. The majority were critically ill, with 84.8% in the ICU and 95.7% with multiorgan failure.50 patients had routine follow up (RF) while 14 patients did not (NF), and 8 patients with unknown outpatient visit status. The median age of death for RF and NF were the same 43.5 (STD=15.53) & 43 (STD=15.71) years, respectively. The genotype distribution, and other characteristics are listed in Table 2. About 44% (n=22) of the RF group were prescribed HU, with 31.8% (n=7) were prescribed a dose > 15mg/kg/dose. This was not a significant difference from the NF group, where 50% (n=7) were prescribed HU, with 42.9% at > 15mg/kg/dose. The median MCV, percentage of HbF were similar. Significant majority in RF and NF groups were prescribed chronic opiates (86% and 78.6%, respectively) with 105 and 95 median MME per day. 42.9% of patients in the NF group had alloimmunization compared to 26% in the RF group.Discussion:Most of the patients had at least 1 severe complications from SCD, and most had other comorbidities (Table 1). This is commensurate with SCD literature showing that the manifestations of chronic end-organ damage increase as patients age which increases the likelihood of early mortality. In our analysis, the median age of death was similar for those in the RF and NF groups across genotypes.HU is a disease-modifying therapy that impacts survival and reduces complications and was FDA approved in 1998, however less than 50% of patients had a prescription. Median HbF and MCV were similar between the 2 groups, suggesting HU adherence was not a factor. This raises concern about accessibility of HU for patients which was not within the scope of this review. Improvement of access and education for patients and clinicians of these therapies is needed to see reduction in mortality. As more of the adult population starts to include those with access to HU since early childhood, future studies can examine what impact that will have on HU adherence, and life expectancy. With the advent of new therapies, it is imperative to study these agents on the patients with SCD complications to evaluate their efficacy in reducing mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Effect of Individualized Pain Plans for Patients with Sickle Cell Disease on Emergency Provider Satisfaction: A Win for the Patient Can be a Win for the Provider

BackgroundSickle cell disease (SCD) is an inherited hematologic disorder that affects approximately 100,000 Americans and results in over 200,000 emergency departments visits annually, largely due to pain (Lanzkron et al). Delay in treatment in emergency room has been a significant barrier to patients with SCD, particularly adults. The objective of this study is to determine the effects of utilizing individualized pain plans for the treatment of vaso-occlusive crisis (VOC) on the satisfaction of healthcare providers in the emergency department (ED).MethodsThe Ohio State University has a comprehensive sickle cell center which creates individualized pain plans for patients who present to the ED with pain related to VOC. In January 2015, these pain plans were implemented into the electronic medical record listed in the overview of the problem sickle cell disease in each chart. In addition to creating pain plans, an interdisciplinary team was formed consisting of hematologists, pharmacists, and ED providers with the goal of education regarding SCD and the new implementation of pain plans. Surveys, using the secure web application, RedCAP, were distributed to the emergency department providers at the OSU ED. Questions included responders' role in the ED, prior experience with treating pain crisis, time to make treatment management decisions for VOC, satisfaction with treatment decision, and the providers view of their relationship with patients. Wilcoxon signed-rank test and Fisher's exact test were applied to evaluate the differences between pre and post survey numeric and categorical responses.ResultsSurveys were sent electronically to 170 ED providers. Sixty-nine responses, making up 40.5% of those surveyed, were obtained from 30 attending physicians, 2 fellows, 22 nurse practitioners or physician assistants, 1 registered nurse, and 14 residents. Of those who answered the survey, 14 had experience with treating pain crisis prior to the implementation of individualized pain plans. Implementation of individualized pain plans led to a reduction in median time to make treatment decisions from 5.5 to 2.5 minutes with a p-value of 0.0161. Provider satisfaction with treatment decisions improved as well (p = 0.0029) (Figure 2). In addition, ED providers felt more satisfied with their relationship with patients (p = 0.0078) (Figure 3). The majority of responders (91.2%) also rated their satisfaction with the treatment decision as either satisfied or very satisfied (Figure 1). Seventy eight percent of those answering the survey rated with relationship with patients as being good or very good (Figure 1). In terms of the ease of finding the pain plan in the electronic medical record, 91.3% of providers found them to be either very easy or easy to locate with 94.12% responding that implementing the plan was either easy or very easy (Figure 4). Regarding efficacy of the pain plans, 89.85% found the pain plans to be either effective or very effective (Figure 5). Finally, of the 36 providers who worked elsewhere, about half of the institutions from which they came did not have pain plans.DiscussionThe results of this study show the importance of utilizing individualized pain plans in the treatment of VOC in the ED. As shown in our prior studies, the implementation of individualized pain plans for patients with SCD resulted in a 48% decrease in time to first opioid in the ED, thereby signifying more prompt treatment (Della-Moretta et al). Not only does the data support an improvement in time to make treatment decisions, which benefit the patients, but providers also appear to view their use as an advantage. Pain plan utilization also leads to an increase in provider confidence in their treatment plans as well as a perceived improvement in patient-provider relationships. This is particularly significant as historically the relationship between emergency room staff and sickle cell patients has been seen as challenging by both patients as well emergency room providers (Haywood et al). Making patient centered individualized pain plans readily available, easily accessible, and simple to enact, can further enhance the relationship between the patient, emergency room, and the hematology team. Ongoing communication and education between all parties is beneficial. With the combination of patient and provider data, we show that a win for the patient can also be a win for the provider. [Display omitted] DisclosuresDesai: Pfizer: Other: Publication Fee, Research Funding; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy.