Impact Of Sickle Cell Disease Research Articles

The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women.

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist.

The Impact of Sickle Cell Disease on Acute Coronary Syndrome and PCI Outcomes: A Retrospective Observational Study

Introduction: Sickle cell disease (SCD) is a genetic disorder that is widely observed on a global scale and known for its substantial negative impact on health and mortality. The purpose of this research was to explore how SCD influences the outcomes of acute coronary syndrome (ACS) and Percutaneous Coronary Intervention (PCI). Methods: A retrospective observational analysis was conducted using the National Inpatient Sample (NIS) data for the year 2020. Adult patients with concurrent ACS and SCD diagnoses were included in the study. Demographic information, clinical characteristics, in-hospital outcomes, and PCI complications were examined and compared between ACS patients with and without SCD. Results: Among a total of 779,895 ACS patients, 1495 had coexisting SCD. SCD patiets exhibited distinct demographic features, such as younger age (mean age: 59 vs. 66 years), predominantly female (53% vs. 35%), and primarily African American (91% vs. 11%). Comorbid conditions such as hypertension and chronic lung disease were more prevalent in SCD patients. While inpatient mortality odds did not significantly differ, SCD patients demonstrated slightly shorter lengths of stay in cases of STEMI and NSTEMI/UA. Notably, SCD patients faced a statistically significant increased risk of coronary dissection, highlighting a unique complication in this population. Although an increased incidence of atrial fibrillation and acute heart failure was observed in SCD patients, statistical significance was not achieved. Conclusions: This study provides valuable insight into the intricate interplay between SCD and ACS outcomes. SCD patients presented with distinctive demographic and clinical profiles that influenced their experience with ACS. The elevated risk of coronary dissection emphasizes the necessity for tailored interventions and careful management in SCD patients. These findings underscore the need for further research to elucidate underlying mechanisms and optimize treatment strategies for individuals with both SCD and ACS.

Health-Related Quality of Life of Omani Adult Patients with Sickle Cell Disease at the Sultan Qaboos University Hospital

Objectives: The quality of life of Omani adults with sickle cell disease (SCD) is not yet known. This study aimed to determine the health-related quality of life (HRQoL) of adult Omani patients with SCD attending a single tertiary center. Methods: A cross-sectional study was conducted among patients with SCD from June to October 2022 at the Sultan Qaboos University Hospital. A validated Arabic version of the 36-Item Short-Form Health Survey (SF-36) was used to assess HRQoL over eight domains. Results: A total of 235 patients with SCD participated in the study, of which the majority were female (74.9%) and 18–35 years of age (64.6%). The lowest HRQoL was reported for the domain of role limitations due to physical health (median score: 25.0; interquartile range [IQR]: 35.0), while the highest was seen for role limitations due to emotional problems (median score: 66.7, IQR: 100.0). Frequent SCD-related emergency department visits/hospital admissions and the adverse effect of SCD on patients’ social lives had a significant negative impact on SF-36 scores for all eight HRQoL domains (p ≤0.05). In addition, the impact of SCD on academic performance and a history of having been bullied due to SCD had a significant negative impact on SF-36 scores for several domains (p ≤0.05). Conclusion: Omani adult patients with SCD reported relatively poor HRQoL in several domains, with various factors found to have significant associations with poorer HRQoL. Healthcare providers and policy-makers should consider offering additional clinical, educational, and financial support to patients to enhance their HRQoL.&#x0D; Keywords: Sickle Cell Disease; Health-Related Quality of Life; Adults; Oman

Impact of Sickle Cell Disease on Acute Coronary Syndrome and PCI Outcomes

Impact of Sickle Cell Disease on Acute Coronary Syndrome and PCI Outcomes

The Quality of Life of Sickle Cell Disease Patients in Saudi Arabia 2023

The quality of life of sickle cell disease patients in Saudi Arabia 2023. Sickle cell disease (SCD) is a genetic blood disorder that affects millions of people around the world. It is caused by a mutation in the hemoglobin gene that results in the production of abnormal hemoglobin, which is the protein responsible for carrying oxygen in the blood. SCD is relatively common in Saudi Arabia, with a prevalence of around 2.3%, while the carrier state for SCD, sickle cell trait (SCT), is estimated to be 3.1%. The southern region of the country has the highest prevalence of both SCD and SCT, followed by the eastern region, with lower rates in the central and northern regions. The high prevalence of SCD and SCT in Saudi Arabia poses significant challenges to the healthcare system, with individuals experiencing complications such as pain crises, infections, and stroke, leading to increased hospitalizations and costly treatments. The government has taken steps to address this issue through newborn screening programs and comprehensive care provision, but further efforts are required to ensure equitable access to healthcare for all affected individuals. The disease can have a significant impact on the quality of life of patients due to its chronic nature, pain, and complications. In this study, we aimed to comprehensively investigate various aspects of SCD patients' experiences in Saudi Arabia. We explored the experiences of SCD patients, focusing on their encounters with pain, hospitalizations, and interactions with healthcare providers, the impact of SCD on the social lives and relationships of patients and the educational and support needs of both SCD patients and their families By addressing these research objectives, we gain a comprehensive understanding of the challenges and needs of SCD patients in Saudi Arabia, ultimately contributing to the development of more patient-centered and effective care strategies. Data Collection methods, instruments used, measurements: Patients were recruited through treating doctors during routine consultations utilizing an online based comprehensive survey. Result: The recruitment period for this study was from March 1, 2023, to the end of June of the same year. A total of 75 patients participated in the survey. However, only 50 responses were included in the analysis due to missing or conflicting data found in the excluded answers. The median age of the surveyed patients was 28 years, indicating an improvement in the care provided compared to previous published articles. Among the participants, 66.7% were males, and all the responses came from individuals affected by the disease. The majority of the patients (83.3%) resided in the southern region of the kingdom, followed by (16.7%) from the eastern region. Regarding patient support, all included participants stated that their support came solely from their families, as they declined any support from other patients, religious groups, or healthcare professionals. The main sources of support were the parents, followed by life partners and siblings. Although the patients expressed satisfaction with their family support, (50%) were unsure if support from outside the family was necessary. Regarding pain status, 50% of the patients reported experiencing pain more than three times in the last six months. Medical attention was sought in 50% of these cases, and 33.3% of the attacks required admission. In managing their crises, all patients used opioid-based analgesics. However, only (66.7%) used hydration in addition to home remedies, hot compressions, and local treatments, while (16.7%) used non-opioid-based medications. Despite experiencing emotional distress due to the disease symptoms, anxiety, and feelings of being dismissed, none of the patients sought emotional support from certified professional personnel. The disease had a notable impact on the professional lives of the patients, with 50% being unemployed, and others considering quitting their jobs, refusing promotions, or needing job assistance. The treatment goals from the patients' perspective were to reduce disease complications, improve their quality of life, and decrease pain crises and hospital admissions. Unfortunately, less than 49% of the patients achieved these treatment goals with the provided medications.

Sickle Cell Health Awareness, Perspectives, and Experiences (SHAPE) Survey: Perspectives of Physicians in Gulf Cooperation Council Countries on Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a genetic disorder that adversely impacts patients' physical and emotional well-being, yet research on the impact of SCD on quality of life is limited. The prevalence of SCD across Gulf Cooperation Council (GCC) countries ranges 0.24-5.8% (Abu-Shaheen et al. Expert Rev Hematol 2022). The Sickle Cell Health Awareness, Perspectives, and Experiences (SHAPE) survey aimed to broaden understanding of the global burden of SCD. This analysis reports the experiences of physicians in GCC countries treating patients with SCD who participated in the SHAPE survey within the context of insights obtained globally. Methods: Physicians from Brazil, Canada, France, Germany, the UK, the US, and 2 countries in the GCC (Saudi Arabia and the United Arab Emirates [UAE]) completed a 12-minute online survey comprising close-ended questions about their experiences of treating patients with SCD. Physicians practicing for 3-35 years and currently caring for ≥10 patients with SCD were eligible. Results:Of 219 physicians globally who responded, 30 (13.7%; Saudi Arabia and the UAE, n=15 each) were from GCC countries. Physicians in GCC countries on average were caring for 16 patients with SCD and had 16 years of experience treating patients with SCD. The most common symptoms of SCD reported to physicians in GCC countries were bone aches (95%) in patients aged ≤11 years, fatigue/tiredness and bone aches (92% each) in patients aged 12-17 years, and bone aches (100%) in patients aged ≥18 years. Bone aches and yellow eyes/skin/nails were symptoms reported by a significantly higher proportion of patients in all age groups to physicians in GCC countries than all surveyed physicians (Figure 1). Most physicians agreed early treatment of SCD can help with managing/preventing severe symptoms (80% in GCC countries vs 87% globally) and that treating hemolytic anemia can improve most aspects of SCD including, reducing end-organ damage (87% vs 84%). A significantly greater proportion of physicians in GCC countries, compared with all surveyed physicians, reported they were confident in their knowledge of the consequences of hemolytic anemia (93% vs 50%), and they were significantly more likely to attribute the development of SCD complications such as chronic anemia, kidney damage, and blood clots to hemolytic anemia (Figure 2). A significantly greater proportion of physicians in GCC countries, compared with all surveyed physicians, agreed end-organ damage is unavoidable (87% vs 59%), and they were reluctant to discuss the potential future challenges/complications of SCD with a patient or their family (57% vs 37%). Most physicians agreed they were optimistic about future treatments for SCD (73% in GCC countries vs 81% globally). A significantly greater proportion of physicians in GCC countries reported considering the cost/benefit ratio to the patient and/or health care system before recommending a treatment compared with all surveyed physicians (87% vs 64%). Physicians in GCC countries, compared with all surveyed physicians, reported a significantly smaller proportion of patients were treated with hydroxyurea (24% vs 43%) and opioids (10% vs 29%). The top concerns physicians in GCC countries had were their patients not understanding the long-term effects/progression of SCD (47%), only seeking treatment/care when experiencing crises (47%), and lack of community support for patients (40%). Physicians reported wanting more support to educate their patients about the long-term effects of SCD (93% in GCC countries vs 83% globally). Conclusions: Physicians in GCC countries identified the symptom(s) most frequently reported by patients aged ≤11 years and ≥18 years as bone aches, and by patients aged 12-17 years as bone aches and fatigue/tiredness. Most physicians in GCC countries agreed end-organ damage is unavoidable, but over half were reluctant to discuss the potential future complications of SCD with patients and their families. Findings from the SHAPE survey underline the need for treatments that target specific SCD symptoms and delay end-organ damage, as well as the need of physicians in GCC countries for greater support when treating patients with SCD.

Exploring Factors Linked to Home-Reported Acute Pain Events and Pain Crises in Sickle Cell Disease (SCD) through Flare Tracking in the Ascend Study

Introduction: Pain is a prominent symptom in sickle cell disease (SCD) and often broadly categorized as persistent chronic pain or more intense acute pain episodes compared to regular chronic pain experiences. Many research studies focus solely on pain events requiring healthcare utilization, neglecting those experienced at home, which may cloud the understanding of an individual's daily experience in managing their symptoms. Capturing home-reported evidence is crucial for comprehending SCD's impact on patients and potential effects of medical interventions. Objective: The objective of the Ascend Study was to collect individuals' experiences with pain events in SCD, employing a flexible, home-reported outcomes data collection methodology in Folia Health's mobile and web-based platform. Methods: The Advarra IRB-approved study recruited individuals with any genotype of SCD in the U.S., aged 13 and above, and caregivers of children aged 4 to 12. E-consent and data collection occurred through the Folia platform, where participants selected and tracked relevant symptoms (including, but not limited, to pain-specific symptoms) and treatments, along with health-related quality of life, over the course of 3 months per participant. Baseline severity scores were collected on a 1 to 10 Likert scale for symptoms that were pre-selected by participants at the start of the study. Participants also directly reported potential acute pain events and pain crises experienced in monthly surveys. Detailed flare tracking was set up for four symptom types (chronic pain, acute pain, pain crises, pain and discomfort), enabling structured follow-up questions on select pain flare events. Flare tracking was activated if participants reported a 2-point increase in severity compared to self-identified baselines or opted to track a pain symptom outside of their pre-selected routine. Overall pain burden was collected by participants who routinely tracked all of these various pain experiences, comprising the Ascend Study's home-reported pain hierarchy (Figure A). Results: 89% (n=59) of tracking participants reported experiencing a potential pain crisis for at least 1 month through monthly surveys. Analysis using the flare threshold applied to all pain symptoms tracked (sensitivity 77.5%; specificity 44.9%) identified 2,660 potential pain flare events. Among participants, 86% (n=57) experienced at least one flare event based on the flare threshold. On average, each participant had 24.9 flare days. Flare events identified by the threshold included 9 pain types tracked on a 1-10 Likert scale and 26 pain types tracked as binary “yes/no.” A total of 812 potential pain flare events reported by 46 participants prompted flare tracking follow-up questions (Table 1). Increases in chronic pain were more common than new types. 74% of these participants (n=34) opted to provide additional information through flare tracking in 282 pain flare events. Real-time flare tracking was reported in 85% of flare tracking events. From follow-up responses, most common classifications of pain were stabbing(188, 30.3%), pulsing or throbbing(144, 23.2%), and dull or aching(143, 23.0%). The back (155, 15.7%) and leg (268, 27.2%) were the most prevalent pain locations, with weather (177) and seasonal change (92) identified as potential triggers. Top flare descriptors included ‘can't do normal activities’ (84, 24.4%) and ‘not getting better with home pain meds’ (78, 22.7%). Conclusion: The Ascend Study provides detailed insights into SCD acute pain experiences, showing a high percentage of real-time flare tracking. Chronic pain flares were frequently reported, back and leg pain being the most prevalent locations, and seasonal changes identified as potential triggers. While the flare threshold analysis identified many potential pain flare events, the method's sensitivity might lead to lower specificity for pain flare events and the inclusion of potentially non-flare events. Findings provide valuable insights into the acute pain experiences of individuals with SCD, emphasizing the significance of capturing home-reported evidence to improve patient care and SCD therapies.

Age of Onset of High Transcranial Doppler Measurements Predicts Discrepant Cognitive Profiles in Children with Sickle Cell Disease

Background: Children with Sickle Cell Disease (SCD) have documented compromises in neurocognitive functioning, with notable weaknesses in executive functioning. There is limited published research to define the impact of SCD on the development of visual spatial processing, which is the brain's ability to use and interpret visual stimuli and then apply it to novel situations. We hypothesized that the risk for deficits in visual spatial processing is correlated to high velocity transcranial dopplers (TCD) measurements and the age at which a high TCD velocity first occurred. Our team hypothesized that younger age at time of initial high TCD is associated with a larger impact on visual spatial skills in school aged children. Methods: This review includes data from standard of care practices within our pediatric multidisciplinary sickle cell program. Our clinic began offering neurocognitive screenings in January 2023 to patients who are school entry age (between 5 to 6 years old) or older. Children are identified to participate in screening based on age, parental interest, and provider recommendation. Patients ranging in age from 5 to 15 years of age were screened using either the Weschler Preschool and Primary Scale of Intelligence, fourth edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, fifth edition (WISC-V). Retrospective chart reviews were performed to identify relevant data including TCD and MRI results. The Visual Spatial Index (VSI) is a primary index obtained from the Wechsler standard batteries. VSI assesses a child's ability to construct designs utilizing visual spatial reasoning, attention to visual detail, and visual-motor integration. The average child can demonstrate these skills at age 5 by mentally rotating an object such as a block and matching it with a picture or into a shaped hole. This requires the appropriate development of the basal ganglia, thalamus, parietal lobe, and temporal lobe. The Mean Index Score (MIS) is a broad representation of all cognitive domains measured on the assessment. The difference between the obtained VSI score and a child's MIS is used to determine whether a statistically significant difference exists within the Wechsler assessment system. The difference between the VSI and MIS is compared to a critical value, and if the difference of the VSI and MIS is greater than the critical value then we can say with confidence (p&amp;lt;0.05) that the difference in scores is not due to chance. Chi-square was then used to explore the relationship between the presence of a high TCD before age 5 (the age at which primary visual spatial skills are onboard) and the presence of a statistically significant visual spatial skill weakness. Results: 11 children (mean age 9.73 years; 82% Hemoglobin SS and 18% Hemoglobin SC) were assessed during the first 6 months of this new protocol. 27% (3) of the children had both a high TCD prior to age 5 and a statistically significant (p&amp;lt;0.05) visual spatial weakness, 9% (1) had only high TCD before age 5 but not VSI weakness, and 64% (7) had neither. Due to the small sample size, we used Fisher's exact to test the hypothesis that these two categorical variables (high TCD velocity before age 5 and VSI weakness) were related (P&amp;lt;0.05, P=0.024). We rejected the null hypothesis and found evidence to support a relationship between the presence of high velocities in early childhood and visual spatial skills deficit. Therefore, there is clinical indication that high TCD velocities in early childhood impact the development of visual spatial skills. Conclusion: The impact of sickle cell disease on brain development has been explored, but most published data focus on broad executive functioning skills. Our data yields evidence that the presence of high velocities in the brain before age five may be predictive of future visual spatial abilities as measured using standardized measures (i.e., Wechsler Assessments). It is anticipated that further data exploration will inform the optimization of standard of care practices within our clinic. This may include medical practices such as neuroimaging, changing how we communicate with children and their families, and enhanced practices for supporting students at school through IEPs.

Sickle Cell Health Awareness, Perspectives, and Experiences (SHAPE) Survey: Findings on the Burden of Sickle Cell Disease and Impact on the Quality of Life of Patients and Caregivers in Gulf Cooperation Council Countries

Introduction: Sickle cell disease (SCD) is an inherited disorder that adversely impacts the physical and emotional well-being of patients and caregivers, yet research on the impact of SCD on quality of life (QoL) is limited. In a systematic review the prevalence of SCD in Gulf Cooperation Council (GCC) countries ranged 0.24-5.8% (Abu-Shaheen et al. Expert Rev Hematol 2022). The 3 countries with the highest prevalence were Bahrain (1.2-2.1%, 2 studies), Saudi Arabia (0.24-4.5%, 15 studies), and Oman (5.8%, 1 study). The Sickle Cell Health Awareness, Perspectives, and Experiences (SHAPE) survey aimed to improve our understanding of the global burden of SCD. This analysis reports the experiences of patients with SCD and caregivers in GCC countries who participated in the SHAPE survey within the context of insights obtained globally. Methods: The SHAPE survey included patients and caregivers from Brazil, Canada, France, Germany, the UK, the US, and 4 countries in the GCC (Bahrain, Oman [patients only], Saudi Arabia, and the United Arab Emirates [UAE]). Participants completed a 12-minute face-to-face survey (GCC only) or online survey (other countries) comprising close-ended questions about their experiences with SCD. Patients with SCD aged ≥12 years and caregivers aged ≥18 years supporting a patient with SCD were eligible. Results: Of 919 patients and 207 caregivers globally who responded, 150 patients (16.3%; Saudi Arabia n=70, the UAE n=46, Bahrain n=19, and Oman n=15) and 50 caregivers (24.2%; Saudi Arabia n=25, the UAE n=17, and Bahrain n=8) were from GCC countries (Table). Symptoms experienced most frequently by patients in GCC countries and all surveyed patients, respectively, were fatigue/tiredness (91% vs 84%), bone aches (91% vs 69%), and vaso-occlusive crisis (VOC) pain (81% vs 71%). Compared with all surveyed patients, a significantly greater proportion of patients in GCC countries experienced fatigue/tiredness, bones aches, VOC pain, generalized pain, and signs of organ damage (Figure). Symptoms reported by a significantly smaller proportion of patients in GCC countries than by all surveyed patients were poor sleep/insomnia, poor appetite, memory/concentration issues, nausea, yellow eyes/nails/skin, vision difficulties/retinopathy, and leg ulcers. The top 3 symptoms patients in GCC countries reported as being most impactful in terms of the following categories were: (i) relationships/potential relationships (25% VOC pain, 19% low mood/feeling depressed, 16% bone aches); (ii) family (30% VOC pain, 12% bone aches, 11% low mood/feeling depressed); and (iii) long-term health prospects (29% bone aches, 23% VOC pain, 21% signs of organ damage). The average number of missed school/work days in the past month for patients was 3.9 in GCC countries and 7.5 globally. A smaller proportion of patients in GCC countries were optimistic about their future compared with all surveyed patients (35% vs 52%). The biggest concerns of caregivers of individuals with SCD were worsening of symptoms (54% in GCC countries vs 17% globally) and early loss of life (34% vs 39%). Approximately half of caregivers agreed that caring for a person with SCD had a big or noticeable impact on their family (52% in GCC countries vs 50% globally). The majority of caregivers agreed they were well-equipped to care for someone with SCD (80% in GCC countries vs 72% globally). A smaller proportion of caregivers in GCC countries were optimistic about the future of the person they care for with SCD compared with all surveyed caregivers (32% vs 62%). Conclusions: Findings from the SHAPE survey highlight the physical and emotional burden of SCD on patients and caregivers in GCC countries. Patients in GCC countries reported VOC pain, bone aches, and low mood/feeling depressed as symptoms that most affected their relationships/potential relationships and family. Caregivers in GCC countries expressed concerns about early loss of life and worsening SCD symptoms. Overall, these findings underline the need for effective treatments that alleviate symptoms and manage disease sequalae, and for additional resources to improve the QoL of patients and caregivers.

Impact of Sickle Cell Disease on Academic Performance: A Cross Sectional Study.

Sickle cell disease (SCD) is a multisystemic disease that results in diverse clinical manifestations in the form of acute and chronic complications. This study aims to assess the academic achievements of patients with SCD. A cross-sectional study was a study conducted among adult patients with SCD from the eastern province of Saudi Arabia, where SCD is more widespread than in other regions. A total of ninety patients with SCD, whose median age was 32.33 ± 11.84, were retrospectively evaluated. Of the total number, 32 (35.5%) did not obtain a secondary higher education certificate, and five (3.3%) were illiterate. Sixty-three (70%) of the patients were female, indicating no significant association between gender and education level (p-value > 0.05). The patients' mean annual hospitalizations and emergency visits totaling 4.7 and 8.43, respectively, were not significantly associated with education (p-value > 0.05). Throughout the patients' lives, mean blood transfusions and ICU admissions occurred 6.29 and 2.75 times, respectively, which were not significantly associated with education level (p-value > 0.05). However, education was inversely proportional to a history of splenectomy and cholecystectomy (p < 0.05). Laboratory parameters (hemoglobin level, WBC, platelets, and hemoglobin F) showed no significant associations with education level (p-value > 0.05). Patients with sickle-thalassemia exhibited a trend of being better-educated than those without the diseases, but the difference did not reach statistical significance (p-value > 0.05). A linear regression analysis revealed no significant associations among clinical and laboratory parameters. SCD is a multisystemic disease that impacts socioeconomic status, learning ability, and academic achievements. More research is needed to identify factors that predict poor performance. Additionally, intelligence quotient (IQ) and cognitive assessment should be incorporated into early screening programs for SCD in order to implement preventive measures and a thorough investigation of underlying causes.

Evaluating the impact of sickle cell disease on COVID-19 susceptibility and severity: a retrospective cohort study based on electronic health record.

Sickle cell trait/disease (SCT/SCD) are enriched among Black people and associated with various comorbidities. The overrepresentation of these characteristics prevents traditional regression approach obtaining convincing evidence for the independent effect of SCT/SCD on other health outcomes. This study aims to investigate the association between SCT/SCD and COVID-19-related outcomes using causal inference approaches that balance the covariate. We leveraged electronic health record (EHR) data from the University of Chicago Medicine between March 2020 and December 2021. Demographic characteristics were retrieved. Medical conditions were identified using ICD-10 codes. Five approaches, including two traditional regression approaches (unadjusted and adjusted) and three causal inference approaches [covariate balancing propensity score (CBPS) matching, CBPS weighting, and CBPS adjustment], were employed. A total of 112,334 patients were included in the study, among which 504 had SCT and 388 SCD. Patients with SCT/SCD were more likely to be non-Hispanic Black people, younger, female, non-smokers, and had a diagnosis of diabetes, heart failure, asthma, and cerebral infarction. Causal inference approaches achieved a balanced distribution of these covariates while traditional approaches failed. Across these approaches, SCD was consistently associated with COVID-19-related pneumonia (odds ratios (OR) estimates, 3.23 (95% CI: 2.13-4.89) to 2.57 (95% CI: 1.10-6.00)) and pain (OR estimates, 6.51 (95% CI: 4.68-9.06) to 2.47 (95% CI: 1.35-4.49)). While CBPS matching suggested an association between SCD and COVID-19-related acute respiratory distress syndrome (OR = 2.01, 95% CI: 0.97-4.17), this association was significant in other approaches (OR estimates, 2.96 (95% CI: 1.69-5.18) to 2.50 (95% CI: 1.43-4.37)). No association was observed between SCT and COVID-19-related outcomes in causal inference approaches. Using causal inference approaches, we provide comprehensive evidence for the link between SCT/SCD and COVID-19-related outcomes.

Impact of Sickle Cell Disease on Affected Individuals in Nigeria: A Critical Review.

Sickle cell disease is an autosomal recessive disorder of the beta-globin gene, with resultant deformation of the red blood cells and variable clinical outcomes. Nigeria is recognised as the country with the highest burden of sickle cell disease globally. This study aimed at critically reviewing available literature on impact of sickle cell disease in Nigeria. A literature search was carried out on four databases, and a total of 116 articles that met the inclusion criteria were included in the critical review. It was observed that majority of the studies were carried out in South-Western part of Nigeria (47.4%), whilst the North-East had the least number of studies undertaken in this area, more than a quarter of the studies (27.6%) were related to hematologic and serologic screening. Major themes that emerged from this review were morbidity and mortality; prevalence of sickle cell disease; issues relating to blood transfusion; psychosocial impact; and anatomical dysfunction in sickle cell disease. Intervention programs from both government and non-governmental organizations aimed at reducing the burden of sickle cell disease and its socio-economic impact were identified as key to strategies aimed at overcoming challenges associated with the disease. Findings from this study also revealed that education and awareness interventions were central to reducing the prevalence of sickle cell disease in this setting.

Impact of vitamin B12 on the reproductive health of women with sickle cell disease: a narrative review.

Sickle cell disease (SCD) poses an increased risk of infertility, pregnancy complications and maternal and perinatal mortality among women of reproductive age. This risk is particularly higher for women in sub-Saharan Africa, where the disease burden is highest and access to comprehensive health care is limited, as well as in other countries with a high SCD prevalence due to migration. Disease modifying treatments for SCD could directly and indirectly harm the ovaries, potentially compromising quality and quantity of existing oocytes. Therefore, it is essential to explore alternative interventions, such as nutritional modifications that are less harmful and cost-effective in order to improve reproductive outcomes, and enhance the overall well-being of both mother and child in this population. Maintaining optimal levels of B12 may possibly provide benefits to the ovaries and pregnancy by decreasing homocysteine levels, increasing nitric oxide (NO) bioavailability, and promoting antioxidant and anti-inflammatory activities. Individuals living with SCD are more susceptible to vitamin B12 (B12) deficiency. However, there is a lack of clinical data investigating the relationship between systemic levels of B12, its supplementation, and reproductive outcome measures in SCD women. Therefore, this review aims to examine the current evidence regarding the impact of SCD on female reproductive health and the role of B12 in the reproductive biology of women living with SCD.

Structure-based computational design of novel covalent binders for the treatment of sickle cell disease

The quest in finding an everlasting panacea to the pernicious impact of sickle cell disease (SCD) in the society hit a turn of success since the recent discovery of a small molecule reversible covalent inhibitor, Voxelotor. A drug that primarily promotes the stability of oxygenated hemoglobin and inhibit the polymerization of HbS by enhancing hemoglobin's affinity for oxygen has opened a new frontier in drug discovery and development. Despite eminent efforts made to reproduce small molecules with better therapeutic targets, none has been successful. To this end, we employed the use of structure-based computational techniques with emphasis on the electrophilic warhead group of Voxelotor to harness novel covalent binders that could elicit better therapeutic response against HbS. The PubChem database and DataWarrior software were used to design random molecules using Voxelotor's electrophilic functionality. Following the compilation of these chemical entities, a high-throughput covalent docking-based virtual screening campaign was conducted which revealed three (Compound_166, Compound_2301, and Compound_2335) putative druglike candidates with higher baseline energy value compared to the standard drug. Subsequently, in silico ADMET profiling was carried out to evaluate their pharmacokinetics and pharmacodynamics properties, and their stability was evaluated for 1 μs (1 μs) using molecular dynamics simulation. Finally, to prioritize these compounds for further development in drug discovery, MM/PBSA calculations was employed to evaluate their molecular interactions and solvation energy within the HbS protein. Despite the admirable druglike and stability properties of these compounds, further experimental validations are required to establish their preclinical relevance for drug development.

5612576 DEVELOPMENT AND IMPLEMENTATION OF NEUROPSYCHOLOGICAL SCREENING AND EVALUATION SERVICES FOR ADULTS LIVING WITH SICKLE CELL DISEASE: FINDINGS FROM A TWO-YEAR PILOT PROGRAM

Background: Individuals with sickle cell disease (SCD) may experience diffuse brain injury, impacting neurocognitive development. They may also experience overt strokes and silent cerebral infarcts. These infarcts lead to impaired cognitive functioning across various domains including difficulties with aspects of executive functioning, working memory, processing speed, general intellectual abilities, and difficulties with learning. Research suggests the long-term consequences of these deficits in childhood are likely to have an impact on individuals’ lives as adults. Unfortunately, within the United States, neuropsychological screenings and evaluations are not considered a standard of care for SCD. Ensuring individuals with SCD have these services is critical for optimal care and improved health outcomes. Aims: Neurocognitive services are important for early identification, diagnosis, and treatment; and provide information about current level of functioning, including strengths and challenges. Neurocognitive data can inform strategies to increase health knowledge, adherence to appointments/medications, improve quality of life and prevent/reduce mortality rates. In July 2020, we were awarded a two-year grant to develop and implement a neuropsychological screening and evaluation program for adults living with SCD via an outpatient specialty clinic. Methods: Screening measures were used to detect cognitive dysfunction and challenges with attention and executive functioning. Fifty-one patients (18-73 years) were offered a screening, with 39 completing it. Fifteen patients were referred for further evaluation, with 13 completing a three-hour abbreviated neurocognitive evaluation to date. In this presentation, we will report results of these evaluations. Results: Ten patients were female, one transgender woman, and three were male. Ages ranged from 19-49 years (M = 28.5 years +/- 9.8); 12 were Black/African, and two biracial. Diagnoses were SCD-SS (n = 9), SCD-SC (n = 4), and one SCD-SB+ thalassemia. Five patients had had one or more strokes. Almost half (n = 7) performed in the lowest 10% of the normative population on a test of spatial visualization and motor skill. All performances on a test of visual-construction ability and visual memory were in the lowest 20% of the normative population, with six in the lowest one percent. Five performed in the average range or above on a test of cognitive slowing – the remainder scored very low on this test. In terms of areas of strength, many patients scored in the average range in areas such as verbal comprehension and perceptual reasoning, demonstrated persistence and had found ways to compensate for cognitive related difficulties. Summary: With all aspects of the neurocognitive evaluation taken together, we found that consistent with the literature, our patients evidenced challenges with processing speed, working memory, and aspects of executive functioning. While research on the impact of SCD on visual spatial/visual motor, and visual construction abilities is scant, our patients demonstrated notable deficits in this area, warranting further research. Conclusion: Neurocognitive services need to become a standard of care for SCD care. Additionally, as providers we need to better educate our patients on brain health throughout their lifespan and advocate for access to these types of services.

488 - Feasibility of Using the American Time Use Survey to Study the Impact of Sickle Cell Disease and Hematopoietic Cell Transplant on the Daily Lives of Patients and Their Caregivers: A Stellar Study

488 - Feasibility of Using the American Time Use Survey to Study the Impact of Sickle Cell Disease and Hematopoietic Cell Transplant on the Daily Lives of Patients and Their Caregivers: A Stellar Study

Impact of sickle cell disease in shoulder arthroplasty: a matched cohort analysis.

Sickle cell disease (SCD) is a genetic disorder of abnormal hemoglobin synthesis that is known to cause glenohumeral avascular necrosis (AVN). Little has been published on the use of shoulder arthroplasty (SA) for the treatment of glenohumeral AVN in SCD. We report on the clinical and radiographic results and postoperative complications following SA in the patient cohort. A retrospective review was performed identifying 17 primary SAs (9 hemiarthroplasties, 7 anatomic total SAs, and 1 reverse total SA) in patients with a confirmed diagnosis of SCD and a minimum of 2-year follow-up. This cohort was matched (1:2) according to age, sex, body mass index, type of prosthesis, and year of surgery with patients who had undergone hemiarthroplasty or total SA for osteoarthritis (OA) or reverse total SA for cuff tear arthropathy. Outcomes included the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons score, range of motion, and strength measurements in forward elevation (FE), external rotation (ER), and internal rotation (IR). Our cohort included 9 (52.9%) men with a mean age of 43yr. The average follow-up time was 5.9yr. In patients with SCD, SA provided significant improvements in VAS pain (9.1-3.8; P<.001), FE (95°-128°; P<.001), ER (24°-38°; P<.001), IR score (3.2-5.2; P<.001), FE strength (4.2-4.8; P<.001), ER strength (4.1-4.7; P<.001), IR strength (4.1-4.7; P<.001), and American Shoulder and Elbow Surgeons scores (48.6-73.5; P<.001). When compared to the matched cohort, the SCD group demonstrated higher preoperative (9.1 vs. 3.8; P<.001) and postoperative VAS scores (3.8 vs. 1.3; P<.001). Other clinical outcomes demonstrated no significant differences. There were 5 (29%) complications, 2 (11.8%) episodes of sickle cell crisis, and 3 (18%) reoperations in the SCD cohort. When compared to the matched cohort, there were no statistical differences with respect to complications (29% vs. 12%; P=.140) or reoperations (18% vs. 12%; P=.387). SA is an effective treatment modality for glenohumeral AVN in patients with SCD. Patients may expect improvements in pain, function, motion, and strength. However, final postoperative pain relief may be less than those treated with SA without SCD. Unique perioperative management is necessary to mitigate the risk of postoperative sickle cell crises.

The Multidimensional Impact of Sickle Cell Disease in Children on Parents and Family Functioning: A Cross Sectional Study

The Multidimensional Impact of Sickle Cell Disease in Children on Parents and Family Functioning: A Cross Sectional Study

Real-World Evidence on Disease Burden and Economic Impact of Sickle Cell Disease in Italy.

A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients' characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients with ≥1 hospitalization with SCD diagnosis were included from 01/2010-12/2017 (up to 12/2018 for epidemiologic analysis). The index date corresponded to the first SCD diagnosis. In 2018, SCD incidence rate was 0.93/100,000, the prevalence was estimated at 13.1/100,000. Overall, 1816 patients were included. During the 1st year of follow-up, 50.7% of patients had one all-cause hospitalization, 27.8% had 2, 10.4% had 3, and 11.1% had ≥4. Over follow-up, 6.1-7.2% of patients were treated with SCD-specific, 58.4-69.4% with SCD-related, 60.7-71.3% with SCD-complications-related drugs. Mean annual number per patient of overall treatments was 14.9 ± 13.9, hospitalizations 1.1 ± 1.1, and out-patient services 5.3 ± 7.6. The total mean direct cost per patient was EUR 7918/year (EUR 2201 drugs, EUR 3320 hospitalizations, and EUR 2397 out-patient services). The results from this real-world analysis showed a high disease burden for SCD patients with multiple hospitalizations during the follow-up. High healthcare resource utilization and costs were associated with patient' management and were most likely underestimated since indirect costs and Emergency Room admissions were not included.

Sickle Cell Disease (SCD) Burden on Patients Treated With Hydroxyurea (HU): Results from the Real-World Assessment Survey for SCD in Saudi (ROARS)

The prevalence of SCD in the Kingdom of Saudi Arabia (KSA) is one of the highest in the world with up to 2.6% of the population affected. The Real-World Assessment Survey for Sickle Cell Disease in Saudi (ROARS) was conducted to evaluate the impact of SCD on the quality of life (QoL) of this population. Here, we present data on the QoL burden experienced by patients with SCD in KSA treated with hydroxyurea (HU). Between September and December 2021, patients in KSA with SCD (age: 5-65 years) were surveyed (caregivers were surveyed for patients 5-14 years) using structured, bilingual ROARS questionnaires (English/Arabic) through personal quantitative web-assisted telephone interviews. The survey includes the Patient-Reported Outcomes Measurement Information System (PROMIS) global health domain, a validated tool for assessing QoL among SCD patients and caregivers. The survey evaluated topics such as the impact of SCD on QoL, symptoms, impact of SCD on productivity at work/school, and treatment goals. A total of 1011 responses to the survey were collected; of these, 32.3% (n=327) of patients were currently being treated with HU (47% of adult and 17% of pediatric patients surveyed) and are the focus of this analysis. Amongst these patients, the median age (range) was 25 (5-83) years. Patients were responsible for reporting their SCD genotype: 58% of respondents were diagnosed with HbSS (n=189), 26% with HbSC (n=86), 2% with HbSβ0 thalassemia (n=8), and 5% with HbSβ+ thalassemia (n=15). Overall, 35% (adults, n=84; pediatric n=25) of patients in the eastern province were treated with HU, 27% (adult, n=71; pediatric, n=17) in the western province, 24% (adult, n=55; pediatric, n=24) in the southern province, and 14% (adult, n=29; pediatric, n=22) in the central province. Among HU-treated patients, 64% reported never ceasing/stopping treatment, 21% rarely ceased/stopped treatment and 15% of patients cease/stop treatment sometimes, often, or all the time. The most common reason for patients ceasing/stopping treatment was forgetting to take their medication (79%). Of patients who cease/stop treatment sometimes, often, or all the time (n=48), 17% of these stated that their medication was not available while 4% could not afford their medication. The mean (SD) number of VOCs reported by HU-treated patients in the 12 months prior to survey completion was 4.6 (4.09), while 32% (n=104) of these patients reported experiencing ≥5 VOCs in the same period. The most common SCD symptoms (other than VOCs) experienced by HU-treated patients were bone ache (reported by 92% of respondents), fatigue/tiredness (85%), headache (79%), anxiety (61%), joint stiffness (56%) and numbness/tingling (51%). Most HU-treated patients reported poor/fair or good health for all QoL metrics assessed (Figure 1). Almost half of patients (49%) reported that their SCD was impactful/extremely impactful on their emotional wellbeing. Of those treated with HU, 71% of patients reported that HU is effective in treating their SCD symptoms. However, 84% of patients report a desire for alternatives to their current pain management medication while 72% report concerns about the long-term side effects of HU. The most important treatment goals for these patients were improvement in quality of life (82%), improvement in overall symptoms (79%), and reduction in the number of severe pain crises and increase in the number of days free from severe pain crises (79%). A total of 48% of HU-treated patients were bothered by limitations in performing everyday activities; 48% and 55% of patients also reported that their SCD has prevented them from progressing in their career or education, respectively. Patients treated with HU reported missing a mean (SD) of 6.9 (10.4) hours of work in the 7 days prior to survey completion because of their SCD. Access to HU treatment continues to be a challenge, with approximately 70% of patients surveyed not receiving HU. Despite the observed clinical benefit in symptom control, patients receiving HU continue to experience disease burden including substantial impact on QoL and productivity at work/school (as evident from the treatment goals identified by patients). These data highlight the necessity of optimizing HU accessibility and treatment strategies to improve patient outcomes. These data also illustrate the need for novel therapeutic options and management strategies for patients with SCD to target patient-reported treatment goals. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal