Sickle Cell Disease Status Research Articles

Electrocardiographic findings in patients with sickle cell disease: A protocol for systematic review and meta-analysis.

Despite advancements in the management of patients with sickle cell disease (SCD), the involvement of the cardiovascular system in these patients remains a significant concern. Cardiovascular manifestations of SCD are well-documented, with electrocardiography (ECG) serving as a valuable diagnostic tool. Studies have reported a high rate of critical ECG findings in patients with SCD that warrants consideration when managing these patients, indicating the need for proactive cardiac screening and management strategies in this patient population. This study aims to systematically review the literature to identify sociodemographic, clinical, and paraclinical factors associated with ECG abnormalities in patients with SCD. A comprehensive search strategy will be employed across multiple online databases, including PubMed, Embase, Scopus, Web of Science, and Google Scholar, for published and gray literature. Eligible studies will include original articles reporting associations between sociodemographic, clinical, and paraclinical variables and a spectrum of ECG findings in patients with SCD. Independent reviewers will conduct the screening, quality assessment, and data extraction. Quantitative analyses will be performed under a random-effect model using Comprehensive Meta-Analysis software, with subgroup analyses based on SCD status, sickle hemoglobinopathy form, and age group.

Global White Matter Changes and Associations with Cognition in Pediatric Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a genetic blood disorder affecting multiple organ systems, particularly the brain (Pinto, V.M. et al 2019). Neurocognitive deficits can occur in the presence or absence of overt brain injury, such as stroke or silent cerebral infarction (SCI). Using diffusion tensor imaging (DTI) metrics, multiple studies have identified widespread white matter alterations in individuals with SCD. DTI abnormalities, such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD), have been associated with decreased processing speed in this population (Stotesbury et al. 2018). The goals of this study are to 1) define developmental differences in diffuse (brain-wide) white matter microstructure between SCD and control pediatric participants and 2) determine medical and neurocognitive characteristics of pediatric participants with SCD and abnormal DTI metrics. Methods: Thirty-eight participants between 8 to 12 years of age with no prior known history of stroke, SCI, or seizures were recruited for a prospective longitudinal study. Study groups consisted of 28 participants with SCD and 10 sibling or unrelated control participants. This study was a cross-sectional analysis of participants who completed DTI scans and neuropsychological testing at study entry (n=35). DTI was obtained on a 3T Philips research scanner 2.2mm nominal isotropic resolution; 32 diffusion directions obtained at b=700 s/mm 2. Preprocessing, tensor estimation, and calculation of FA and MD maps were performed using DTI Studio/MRICloud and its pediatric DTI atlas. Neurocognitive evaluation was performed and interpreted by a trained psychology associate with supervision from a board-certified neuropsychologist and included intelligence testing (Weschler Intelligence Scale for Children, WISC-5). Statistical analyses were performed using STATA 18 and MATLAB 2022a. We examined cohort-level demographics using chi-square tests, T-tests, and Wilcoxon rank sum tests (Table 1). To examine diffuse differences in white matter microstructure development, we used 19 bilateral white matter regions of interest [ROIs] shown in prior research to be important in patients with SCD with and without SCI. We examined MD and FA values within ANOVA models (each in terms of Group*Age + ROI) to assess group-level differences (SCD vs. control) and group x age interactions. We used ANOVA loadings to compute global MD and FA scores and computed 95% prediction intervals by age based on control participants. We identified participants with SCD with global scores suggestive of white matter microstructural differences (high MD and/or low FA) and compared their overall neurocognitive profiles. Results: The SCD and control participants were similar with regards to age, sex, and full-scale IQ. SCD participants had significantly lower median hemoglobin levels than control participants. There was one control participant who met criteria for SCI. SCD vs. control group status, age, and group x age interactions all significantly impacted our MD model (explaining 0.8%, 1.1%, and 0.8% of total variance, respectively; all p<0.001). MD decreased with age in the combined cohort (β=-9.3±1.6e-7/month) with significant flattening of this trend in children with SCD (group x age interaction: β=+7.9±2.0e-7/month). In contrast, only age significantly impacted our FA model (p<0.001, explaining 1.1% of variance); group status and group x age interactions each explained <0.2% of variance in FA. Four children with SCD had global DTI metrics suggestive of white matter injury (one with high MD and low FA; two with high MD only; one with low FA only). All 4 participants with abnormal DTI metrics had abnormal MRIs, three of whom had SCI and one of whom had lesions that did not meet the size criteria for SCI. Three participants had full scale IQs 1 standard deviation below the expected mean of 100 (<85). Conclusion: We identified differences in global white matter microstructural indices between SCD and control participants with an apparent blunting of expected decreases in mean diffusivity with age. Our continuing longitudinal study will explicitly assess DTI trajectories and implications for neurocognitive functioning in children with SCD.

Enhanced Expression of Heme Oxygenase-1 (HO-1) Among Children with Sickle Cell Disease: Results of the Sickle Cell Disease Genomics of Africa (SickleGenAfrica) Study

Sickle cell disease (SCD) is characterized by intense and chronic intravascular hemolysis that generates multiple erythroid danger associated molecular pattern (eDAMP) molecules in the extracellular space. Extracellular heme is a prototypical eDAMP that causes tissue injury and is associated with multiple complications of SCD including vaso-occlusive crisis, acute kidney injury and acute chest syndrome (ACS). Heme-oxygenase-1 (HO-1) is the rate-limiting enzyme that degrades heme to neutralize its deleterious effects on organ function. Raised extracellular heme is associated with 2.5 higher odds ratio of developing ACS, while HO-1 gene promoter allelic variants that drive robust HO-1 expression are associated with lower ACS-related hospitalization rates among children. Young transgenic homozygous SCD (SS) mice have higher survival rates than adult SS mice from a heme-induced ACS model due to their ability to rapidly degrade excess extracellular heme. While these data suggest that HO-1 may be involved in the well-established higher ACS survival among children, and potentially other ameliorating features of SCD in early development, no study had previously studied HO-1 expression in this patient population. The SickleGenAfrica Network enrolled over 2,000 children and adults with SCD from three sites in Ghana from 2018 to 2021, with consent for use of samples in future studies. The SCD status of participants was confirmed using automated capillary hemoglobin electrophoresis, and serum HO-1 level measured using ELISA. Patients were grouped based on age, using five-year intervals. The median HO-1 level comparisons across groups were performed using the pairwise Wilcoxon test, with Bonferroni correction for multiple comparisons. All analyses were performed using R version 4.3.1. The study included 1,971 patients with SCD, with a median age of 13 years (range 0 - 78), of which 1,067 participants (55%) were female. The majority of patients (1149 ;58%) had HbSS, 589 (30%) had HbSC, 171 (9%) sickle-hereditary persistence of fetal hemoglobin, and 62 (3%) HbS-beta(+). We observed an approximately 3-fold drop-off in median HO-1 levels between the 11-15-year-old (73.9 ng/ml) and 16-20-year-old (25.1 ng/ml) age groups (adj. p<0.001). Furthermore, males had higher average HO-1 levels (85.5 ng/ml) relative to females (63.1 ng/ml) (p<0.001). Our data show for the first time that children with SCD have significantly elevated HO-1 levels relative to adults, with a sharp decline in HO-1 levels during adolescence. HO-1 may serve as a protective SCD factor, contributing to enhanced ACS survival rates in children versus adults. To the best of our knowledge, this is the first study of HO-1 levels in patients with SCD at different ages. Our future work aims to establish whether baseline blood HO-1 levels can predict ACS incidence and severity, in addition to further investigating genetic and epigenetic mechanisms controlling HO-1 expression.

Epidemiology of Maternal Nutritional Status and Risk of Adverse Birth Outcomes in Undernourished Mothers with Sickle Cell Disease: A Systematic Review and Meta-Analysis Protocol.

In pregnancies complicated by sickle cell disease (SCD), the maternal-fetal dyad is at high risk for mortality and morbidity. In healthy pregnancies, maternal nutritional status is a critical factor for the healthy growth and development of the fetus. However, there are no reviews of the current research on the nutritional status of pregnant women with SCD and pregnancy outcomes. First, we aim to assess the burden of malnutrition in pregnant women with SCD. Next, we aim to systematically evaluate if pregnant women with SCD who have poor nutritional status are at increased risk for adverse birth outcomes compared to pregnant women with sickle cell disease and normal nutritional status. We will systematically search multiple electronic databases. Our exposure is pregnant women with SCD and poor nutritional status. The primary outcomes of interest include low birth weight (categorical) and birth weight z-scores (continuous). We will also evaluate maternal and perinatal outcomes as secondary outcomes. We will evaluate the risk of bias and overall certainty of evidence with Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I), and the overall evidence will be assessed using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We will pool findings with a meta-analysis if sufficient homogeneity exists among studies. Findings will be published in a peer-reviewed journal and disseminated to SCD advocacy groups. PROSPERO registration number: 429412.

Evaluating the Discriminatory Ability of the Sickle Cell Data Collection Program's Administrative Claims Case Definition in Identifying Adults With Sickle Cell Disease: Validation Study.

Sickle cell disease (SCD) was first recognized in 1910 and identified as a genetic condition in 1949. However, there is not a universal clinical registry that can be used currently to estimate its prevalence. The Sickle Cell Data Collection (SCDC) program, funded by the Centers for Disease Control and Prevention, funds state-level grantees to compile data within their states from various sources including administrative claims to identify individuals with SCD. The performance of the SCDC administrative claims case definition has been validated in a pediatric population with SCD, but it has not been tested in adults. The objective of our study is to evaluate the discriminatory ability of the SCDC administrative claims case definition to accurately identify adults with SCD using Medicaid insurance claims data. Our study used Medicaid claims data in combination with hospital-based medical record data from the Alabama, Georgia, and Wisconsin SCDC programs to identify individuals aged 18 years or older meeting the SCDC administrative claims case definition. In order to validate this definition, our study included only those individuals who were identified in both Medicaid's and the partnering clinical institution's records. We used clinical laboratory tests and diagnostic algorithms to determine the true SCD status of this subset of patients. Positive predictive values (PPV) are reported overall and by state under several scenarios. There were 1219 individuals (354 from Alabama and 865 from Georgia) who were identified through a 5-year time period. The 5-year time period yielded a PPV of 88.4% (91% for data from Alabama and 87% for data from Georgia), when only using data with laboratory-confirmed (gold standard) cases as true positives. With a narrower time period (3-year period) and data from 3 states (Alabama, Georgia, and Wisconsin), a total of 1432 individuals from these states were included in our study. The overall 3-year PPV was 89.4% (92%, 93%, and 81% for data from Alabama, Georgia, and Wisconsin, respectively) when only considering laboratory-confirmed cases as true cases. Adults identified as having SCD from administrative claims data based on the SCDC case definition have a high probability of truly having the disease, especially if those hospitals have active SCD programs. Administrative claims are thus a valuable data source to identify adults with SCD in a state and understand their epidemiology and health care service usage.

Analysis of the 2007-2018 National Health Interview Survey (NHIS): Examining Neurological Complications among Children with Sickle Cell Disease in the United States.

This study compared neurological complications among a national sample of United States children with or without sickle cell disease (SCD) and evaluated health status, healthcare and special education utilization patterns, barriers to care, and association of SCD status and demographics/socioeconomic status (SES) on comorbidities and healthcare utilization. Data was acquired from the National Health Interview Survey (NHIS) Sample Child Core questionnaire 2007-2018 dataset that included 133,542 children. An affirmation from the guardian of the child determined the presence of SCD. Regression analysis was used to compare the associations between SCD and demographics/SES on neurological conditions at p < 0.05. Furthermore, adjusted odds ratios (AORs) were estimated for having various neurological conditions. Of the 133,481 children included in the NHIS, the mean age was 8.5 years (SD: 0.02) and 215 had SCD. Of the children with SCD, the sample composition included male (n = 110), and Black (n = 82%). The SCD sample had higher odds of having neuro-developmental conditions (p < 0.1). Families of Black children (55% weighted) reported household incomes < 100% of federal poverty level. Black children were more likely to experience longer wait times to see the doctor (AOR, 0.3; CI 0.1-1.1). Compared to children without SCD, those with SCD had a greater chance of seeing a medical specialist within 12 months (AOR 2.3; CI 1.5-3.7). This representative sample of US children with SCD shows higher odds of developing neurological complications, increased healthcare and special education services utilization, with Black children experiencing a disproportionate burden. This creates the urgency to address the health burden for children with SCD by implementing interventions in healthcare and increasing education assistance programs to combat neurocognitive impairments, especially among Black children.

The relationship between nutrition, gut dysbiosis, and pediatric sickle cell pain outcomes: A pilot study.

Nutritional deficiencies are prevalent in sickle cell disease (SCD) and may be associated with worse pain outcomes. Gut dysbiosis has been reported in patients with SCD and may contribute to both nutritional deficiencies and pain. We tested the association of nutrition, fat-soluble vitamin (FSV) deficiency, and gut microbiome composition on clinical outcomes in SCD. Second, we measured the association between diet and exocrine pancreatic function on FSV levels. Using case control design, we enrolled children with SCD (n=24) and matched healthy controls (HC; n=17, age, sex, race/ethnicity). Descriptive statistics summarized demographic and clinical data. Wilcoxson-rank tests compared FSV levels between cohorts. Regression modeling tested the association between FSV levels and SCD status. Welch's t-test with Satterthwaite adjustment evaluated associations between microbiota profiles, SCD status, and pain outcomes. Vitamin A and D levels were significantly decreased in participants with HbSS as compared to HC (vitamin A, p=<.0001, vitamin D, p=.014) independent of nutritional status. FSV correlated with dietary intake in SCD and HC cohorts. Gut microbial diversity was reduced in hemoglobin SS (HbSS) compared to hemoglobin SC (HbSC) and HC, p=.037 and .059, respectively. The phyla Erysipelotrichaceae and Betaproteobacteria were higher in SCD children reporting the highest quality-of-life (QoL) scores (p=.008 and .049, respectively), while Clostridia were higher in those with lower QoL scores (p=.03). FSV deficiencies and gut dysbiosis are prevalent in children with SCA. Gut microbial composition is significantly different in children with SCD with low QoL scores.

5610785 THE EFFICACY OF HEALTH EDUCATION INTERVENTION AND MATERNAL SCREENING ON KNOWLEDGE AND INFANT SCREENING FOR SICKLE CELL DISEASE AMONG PREGNANT WOMEN ATTENDING ANTENATAL CLINICS IN DAR-ES-SALAAM, TANZANIA

Background: Globally, Sickle cell disease (SCD) is one of the most common genetic disease with high childhood mortality 1. Early identification of babies with SCD through newborn screening (NBS) and linking them to care are among the recommended interventions 2. For these to be effective, it is important for pregnant women to have the right knowledge on SCD and motivation to screen their babies. Aim: To assess the efficacy of health education (HE) intervention and maternal screening for SCD on knowledge and the uptake of infant screening for SCD among pregnant women attending antenatal clinics (ANC) in Dar-Es-Salaam, Tanzania. Methods: This was a quasi-experimental study, involved pregnant women attending ANC at Buguruni health center, Mbagala hospital and Sinza hospital in Dar Es Salaam between August 2020 to April 2022. A structured questionnaire was used in data collection. Knowledge on SCD (poor if score <7; good if score 7-10) was assessed to all participants before and after two sessions of HE3, and participants in Buruguni and Mbagala were also screened for SCD using Sickle SCAN point-of-care test (BioMedomics Inc, USA). We computed effectiveness of HE intervention as the post-intervention minus baseline knowledge score. Two-sample test of proportions, univariate and multivariate logistic regression were used to analyze the efficacy of HE intervention and also predictors of infant diagnosis. Before enrollment, written informed consent was obtained from participants, parents/guardian of participants <18 years of age. Results: A total of 467 pregnant women completed two sessions of HE intervention where 221 (47.3 %) participants were screened for SCD; Out of 221 screened participants, 203 (91.9%) remembered their sickle cell status 3 to 4 months after screening. The proportion of participants with good knowledge on SCD had significantly increased from 12.4% at baseline to 85.9% following the education intervention p-value <0.0001. HE provided was effective to 85.3% of participants, and was 2.45 times higher among those who shared the received education with others than those who did not share (AOR = 2.45; 95% CI = 1.38 to 4.36). The uptake of infant diagnosis was 5.39 higher in infants whose mothers shared the received education than those who did not share (AOR = 5.39; 95% CI = 1.18 to 24.67). 5.4% of babies (26/170 babies) were screened post-delivery, and 3 of them had Hb SS. Mothers who were employed had 6.49 higher odds of screening their infants than housewives (AOR = 6.49; 95% CI =1.52 to 27.79). Maternal status was also seen to associate with infant diagnosis whereby those with hemoglobin S (AS or SS) had 13.28 times higher odds of screening their infants than those who did not know their SCD status (AOR = 13.28; 95% CI = 4.11 to 42.86). There was no difference in odds of the baby being screened for SCD between mothers who had Hemoglobin AA as compared to mothers who were not screened for SCD (AOR = 1.62; 95% CI = 0.56 to 4.84). Conclusion: This study has demonstrated that maternal HE and maternal screening for SCD are feasible and effective interventions in increasing knowledge as well as improving the uptake of infant screening for SCD. These interventions are strongly recommended to be included in the comprehensive care package for pregnant women attending antenatal clinics, particularly in areas with a high burden of SCD.

5597311 THE EFFECT OF MUSIC AND DANCE AS FORMS OF PHYSICAL ACTIVITY ON THE HEALTH STATUS OF PEOPLE WITH SICKLE CELL DISEASE: A SYSTEMATIC REVIEW OF THE LITERATURE

Background: Physical activity and exercise are not always evident in people with Sickle Cell Disease (SCD). Therefore, other forms of exercise therapy such as music and dance are often favoured but their effect on the health status of people with SCD has only been studied to a limited extent. This research is performed by three students of Rehabilitation Sciences and Physiotherapy from the Faculty of Medicine and Health Sciences at the University of Antwerp. They chose the topic from a strong personal interest, namely one of the students has a family member with SCD, and all have a shared interest in music and dance. Aims: The objective of this systematic review of the literature is to examine the effectiveness of music and dance as forms of physical activity on the health status of people with SCD. Methods: A systematic search of the literature, including studies between 2010 and 2021, was conducted using the electronic medical databases Pubmed and Web of Science. The search strategy incorporated keyword combinations related to people with SCD, music, dance, physical activity and health status. The ROBINS-1, Rob 2.0 and Qualsyst tools were used to evaluate the risk of bias. Results: After the screening process, ten articles were included. Published studies were conducted in Brazil, the USA, France and Saudi Arabia. The total number of participants was 1122 and the age varied between 7-58 years. From all 1122 participants, 550 (49.02%) were women, 407 (36.27%) men and 165 (14.71%) were unspecified. Most studies conclude that exercise and music therapy have positive effects on the health status and quality of life of people with SCD, significantly improving pain intensity and mood. The main finding is that standardized, supervised, and patient-adapted moderate-intensity endurance-exercise training can be safe in patients with SCD without an increased risk for a vaso-occlusive crisis. However, due to heterogenous intervention programs, varying risk of bias and the inclusion of small sample sizes it remains difficult to draw general conclusions. Surprisingly, none of the studies explicitly explored the effect of dance movement therapy in this population. Summary - Conclusion: To our knowledge, this is the first systematic review to identify the effect of music and dance as forms of physical activity on the health status of people with SCD. Both activities have a wide range of physical and mental benefits and can be a way to stay fit for people of all ages. Further studies with a randomized study design are needed to explore the impact and long-term effects and to compare different forms of musical engagement and dance interventions in individuals. Although multiple benefits have been described, more evidence would motive healthcare professionals to include music and dance therapies as a standard of care in the treatment of people with SCD.

Characterisation of medical conditions of children with sickle cell disease in the USA: findings from the 2007–2018 National Health Interview Survey (NHIS)

ObjectivesWe used the National Health Interview Survey (NHIS) data set to examine the prevalence of comorbid medical conditions; explore barriers to accessing healthcare and special educational services; and assess the...

Abstract 65: Cerebrovascular Reactivity Imaging Is Well Tolerated In Children With And Without Sickle Cell Disease

Background: Cerebrovascular reactivity (CVR) refers to a stimulus-induced change in blood flow, reflecting hemodynamic reserve. Carbon dioxide (CO 2 ) stimulus increases cerebral blood flow (CBF), and exogenous noninvasive CO 2 with concurrent MRI is an established CVR method in adults. However, children with and without sickle cell disease (SCD) have increased resting CBF compared to adults, and few studies have examined CVR in children. Our objective was to determine tolerability of CO 2 CVR MRI in children with and without SCD. Methods: Children undergoing CO 2 CVR MRI had post-scan assessments of their experience and comfort during CVR testing. This included a preference rating ranking 8 experiences, including CVR MRI, in order from most to least enjoyable, a 6-point comfort scale, and a yes/maybe/no question asking if they would do CVR MRI again. The 8 preference items were grouped into quartiles for analysis. The Wilcoxon test was used to compare comfort rating based on SCD status and quartile preference rankings. Spearman’s correlation was used to compare peak end-tidal CO 2 with comfort rating. Results: Nine children with SCD and 22 controls ages 8-21 years old completed CVR MRI, with a median peak end-tidal CO 2 of 50 mmHg [IQR 47, 51]. No child had a serious adverse event. On a 6-point scale, the median comfort rating was 4 (slightly uncomfortable) [IQR 2,4]. There was no difference in comfort based on SCD status (p=0.70) or peak end-tidal CO 2 (p=0.65). Across all participants, CVR fell in the 3rd preference quartile. CVR rated similarly to visiting the dentist (p=0.95), but was better than throwing up (p=0.03). Despite ranking the scan in the 3 rd quartile, the majority reported willingness to repeat CVR MRI, and only one participant (control) said they would not. Conclusion: Noninvasive CO 2 CVR imaging is safe and tolerable in children with and without SCD. After completing the session, most children would be willing to undergo similar testing again.

The efficacy of maternal health education and maternal screening on knowledge and the uptake of infant screening for sickle cell disease in Dar-Es-Salaam, Tanzania; a quasi experimental study

BackgroundGlobally, Sickle cell disease (SCD) is one of the most common genetic disease with high childhood mortality. Early identification of babies with SCD through newborn screening (NBS) and linking them to care are among the recommended interventions. The purpose of this study was to assess the efficacy of maternal health education and maternal screening for SCD on knowledge and the uptake of infant screening for SCD among mother-infant pairs attending antenatal clinics at Government health facilities in Dar-es-salaam, Tanzania. MethodsThis study was a pre-test post-test, quasi-experimental which involved pregnant women attending antenatal clinics at three hospitals; Mbagala hospital, Sinza hospital and Buguruni health center in Dar Es Salaam. A structured questionnaire was used in data collection. Knowledge on SCD was assessed for all participants before and after two sessions of health education. Participants in Mbagala and Buguruni were also screened for SCD using Sickle SCAN point-of-care test (BioMedomics Inc, USA). The efficacy for health education intervention was computed as the post-intervention minus baseline knowledge score. For proportions, a two-sample z-test was used. Univariate and multivariate logistic regression were used to analyze the efficacy of health education intervention and also predictors of infant diagnosis. ResultsFor two sessions of health education intervention, a total of 467 pregnant women completed the sessions. During antenatal visits, a total of 218 were screened for SCD. The proportion of participants with good knowledge of SCD had significantly increased to 85.9% from 12.4% at baseline following the education intervention. In multivariate analysis, sharing the received education on SCD was an independent predictor of the efficacy of health education intervention. Maternal occupation, maternal SCD status as well as sharing the received education on SCD were independent predictors of the uptake of SCD infant diagnosis.ConclusionThis study has demonstrated that maternal health education and maternal screening for SCD are feasible and efficacious interventions in raising knowledge and improving the uptake of infant diagnosis for SCD. These interventions are strongly recommended to be included in the comprehensive care package for pregnant women attending antenatal clinics, particularly in areas with a high burden of SCD.

P-031: TRANSITION FROM LONG TERM HIGH DOSE FULL AGONIST OPIOIDS TO BUPRENORPHINE IN THE INPATIENT SETTING FOR PEDIATRIC PATIENTS WITH SICKLE CELL DISEASE: A MODIFIED INDIVIDUALIZED MICRO INDUCTION APPROACH. A SINGLE CENTER EXPERIENCE

Purpose: Sickle cell disease (SCD) has a global incidence of approximately 300,000/yr. About 100000 individuals live with SCD in the US. The hallmark of SCD is anemia, recurrent acute painful Vaso occlusive episodes (VOE’s) and progressive multi-organ involvement. VOE’s begin in infancy (dactylitis) and increase in frequency with age. Prompt administration of short-term full agonist opioids, combined with Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) is the mainstay of VOE treatment. However, a subset of patients will develop chronic pain (CP) beginning early in adolescence. Long term opioid therapy has been used to treat SCD CP due to a lack of available alternatives. LTOT for CP has been proven to have poor efficacy and high toxicity and is associated with reduced quality of life. Buprenorphine is a partial opioid agonist, which physiologically exerts a ‘ceiling effect’ with less opioid related toxicity and thus is a safer option for patients who experience poor efficacy and increased toxicity from LTOT. Materials and methods: From 12/2020 to 02/2022, 10 patients met program eligibility criteria: SCD diagnosis, debilitating CP, receiving >90 morphine equivalents daily, (both outpatient and inpatient totals) with poor analgesic response. Each patient underwent a comprehensive evaluation of SCD status and other comorbidities, a psychological evaluation and participated in several education sessions with their caregiver prior to enrollment. Buprenorphine was initiated using a micro induction regimen that comprised of transdermal Buprenorphine 10mcg/hour or 20 mcg/hour on day 1 and adding buccal Buprenorphine/Naloxone starting on day # 2 or 3 and titrating upwards to individualized requirements. Full opioid agonists were slowly weaned down. Symptoms of withdrawal were monitored using the clinical Opioid withdrawal scale (COWS). Results: Patient were between ages between 12-19 years, with median of 18 years. 7 were Female. All 10 patients were successfully transitioned off LTOT onto a Buprenorphine formulation and none experienced withdrawal symptoms. Of the 10 patients, 7 remain on Buprenorphine beyond 3 months post induction with reductions in both acute care utilization and inpatient hospitalization. Utilization data: 6-months pre buprenorphine: Emergency room (ER) visits ranged from 3-20 with a mean of 9 encounters. Number of inpatient admissions were from 3-10 with a mean of 5.7 and length of stay between 3-19.3 days with a mean of 8.75 days. In the 3-6 months post Buprenorphine: number of ED encounters ranges from 1-7 with a mean of 2.2; the number or admissions range from 0-5 with a mean of 1.6 and length of stay ranged between 0-15 days with a mean of 4.85 days. Conclusion: Pediatric and young patients with SCD on high dose LTOT can be transitioned successfully to buprenorphine in the inpatient setting, using a modified micro induction titration regimen. A system wide multidisciplinary approach to include nursing, emergency department, pharmacy, psychologists and psychiatrists and an education dissemination plan is needed. Both patients and parents need to be ready for an alternative in order to achieve long term success. With the increasing reports of the use of Buprenorphine for CP in SCD, large prospective multi-center clinical trials are warranted. The authors do not declare any conflict of interest

Oxygen Saturation in Primary Teeth of Individuals With Sickle Cell Disease and Sickle Cell Trait.

PurposeTo determine oxygen saturation in the pulp of primary teeth in children with sickle cell disease (SCD) and sickle cell trait (SCT) for establishing the usefulness of pulse oximetry in screening and monitoring of SCD or therapy.Materials and MethodsA cross-sectional study among 30–60 months children with sickle cell disease (SCD) and sickle cell trait (SCT) compared with healthy children (HbAA). A pulse oximeter (BCI 3301) recorded oxygen saturation on six anterior primary maxillary teeth and on index fingers. Data were analyzed using SPSS version 20.0. Mean oxygen saturation for teeth and fingers was calculated. Comparison of Mean across groups was done using post hoc analysis in one-way ANOVA (Bonferroni test). Pearson correlation coefficient was calculated for mean oxygen saturation on fingers and teeth. Level of significance was set at 0.05.ResultsAltogether 360, 102, and 96 teeth were examined from children with SCD, SCT, and HbAA respectively. 53% of participants were girls. The mean age of participants was 46.3 months ± 9.4 SD. Low mean oxygen saturation (77.5%) was recorded from teeth of children with SCD relative to those with SCT and HbAA (>86%; P = 0.00). There was no statistically significant difference in oxygen saturation on teeth between children with SCT and HbAA. The mean oxygen saturation on fingers was found to be above 97.2% regardless of sickle cell status. There was no correlation between oxygen saturation on teeth and fingers.ConclusionPulse oximeter detected a lower oxygen saturation in dental pulp of primary teeth of participants with SCD (HbSS) relative to those with SCT (HbAS) and HbAA. Oxygen saturation on fingers remained unaffected regardless of sickle cell disease status. Although more studies are needed, our study shows that when other conditions affecting peripheral tissue oxygen delivery are ruled out, the low pulse oximetry in primary teeth may be indicative of SCD. The oximeter may also be useful in monitoring response to SCD therapy targeted at improving oxygen carrying capacity and delivery.

Low Mortality and High Severe Maternal Morbidity in Pregnancy Among People With Sickle Cell Disease [A174

INTRODUCTION: Pregnancy in people with sickle cell disease (SCD), who are predominantly Black, is high-risk. This study’s purpose is to update risk estimates of severe pregnancy outcomes in SCD and define the excess risk attributable to SCD. METHODS: We analyzed pregnancy-related admissions in the 2012–2018 National Inpatient Sample (NIS) and compared rates of the Center for Disease Control and Prevention’s Severe Maternal Morbidity (SMM) Index in SCD to the general unaffected population (GP) and the unaffected Black population (UB). The composite SMM excluded transfusion and vaso-occlusive crisis. Multivariate logistic regression was used to calculate odds ratios and excess risk fractions, controlling for age, multiple gestation, socioeconomic variables, and hospital characteristics. RESULTS: There were 8,121,002 pregnancy-related admissions, 6,610 among people with SCD (87% Black). There were few maternal deaths in SCD pregnancies (&lt;10). SCD pregnancies were over three times as likely to experience SMM than GP or UB pregnancies (GP: OR 4.63, 95% CI 4.16–5.16, P&lt;.001; UB: OR 3.33, 95% CI 2.97–3.75, P&lt;.001). SCD pregnancies had higher odds of hysterectomy (GP: OR 2.24, P=.002; UB: OR 1.68, P=.09), sepsis (GP: OR 6.72, P&lt;.001; UB: OR 5.54, P&lt;.001), venous thromboembolism (GP: OR 9.89, P&lt;.001; UB: OR 6.24, P&lt;.001), and cerebrovascular event (GP: OR 13.94, P&lt;.001; UB: OR 10.90, P&lt;.001). In SCD pregnancies, excess risk for composite SMM was attributable to SCD status (70%; 95% CI, 67–73%), Black race (31%; 95% CI, 30–32%), and public insurance (14%; 95% CI, 14–15%). CONCLUSION: Contemporary data identifies SMM-, race-, and insurance-based disparities in SCD pregnancies, highlighting the need for disease-specific, pharmacotherapeutic interventions during pregnancy, and requires further prospective validation.

Sickle cell disease prevention: How prepared are the senior secondary school students in Surulere Local Government Area, Lagos, Nigeria?

BackgroundSickle cell disease (SCD), a common hereditary disease, can be prevented by preparing young people ahead of the conception of an affected foetus.AimTo assess the knowledge and attitude regarding SCD amongst senior secondary school students in Surulere Local Government Area (LGA), Lagos, Nigeria.SettingSenior secondary schools in Surulere LGA.MethodsThis was a descriptive cross-sectional study amongst 300 senior secondary school students. Data were collected using a self-administered questionnaire and analysed using Stata16. The Chi-square and Fisher’s exact tests were used to determine the association between categorical variables. The level of significance was predetermined at p < 0.05.ResultsThe mean age of the respondents was 15.2 (±1.3) years, with a male-to-female ratio of about 1:2. The majority (90.0%) of the respondents were aware of SCD, 63.0% had good knowledge, although less than half of them (46.3%) knew SCD to be a blood disorder, whilst about two-thirds (53.1%) knew that it was an inherited condition. About one fifth (24.4%) of them knew about prevention by genetic counselling. The majority (97.0%) of them had a positive attitude towards SCD. Over two-thirds (72.6%) were aware of their genotype. The prevalence of SCD was 2.0%, whilst 18.9% of them were carriers of the sickle cell trait. Knowing their SCD status but not necessarily their genotype was significantly associated with their attitude towards the disease (p = 0.014).ConclusionThe prevention of SCD was not known to the majority, and better attitudes were more likely when the SCD status was known. Therefore, routine screening and counselling could potentially aid SCD control.

Prevalence of Hemoglobin-S and Baseline Level of Knowledge on Sickle Cell Disease Among Pregnant Women Attending Antenatal Clinics in Dar-Es-Salaam, Tanzania.

Background: Sickle cell disease (SCD) is the single most important genetic cause of childhood mortality globally. Newborn screening (NBS) is the recommended intervention aimed at early identification of babies with SCD and their linkage to care. To ensure success of NBS, pregnant women need to have the required knowledge on SCD and therefore motivation to screen their babies. Objective: The aim of this study was to determine the prevalence of hemoglobin-S and assess the baseline level of knowledge on SCD among pregnant women attending antenatal clinics in urban settings in Dar-es-Salaam, Tanzania. Methods: This cross-sectional study was conducted between August 2020 and February 2021, involving 600 pregnant women at 20–28 weeks of gestation attending antenatal clinics at Buguruni Health Center, Mbagala Hospital, and Sinza Hospital in Dar-es-Salaam, Tanzania. We administered a structured questionnaire to all participants to assess socio-demographic characteristics and baseline level of knowledge on SCD, where those scoring 7 or higher out of 10 questions were considered to have good knowledge. We screened for SCD a total of 300 participants from two centers (Buguruni Health Center and Mbagala Hospital) by using Sickle SCAN point-of-care test (BioMedomics Inc., United States). We used SPSS version 23 to analyze the data. On determining the association between level of knowledge and socio-demographic factors, we used Pearson’s Chi-square and multivariate logistic regression in ascertaining the strength of associations. Results: Of the 600 participants, the majority were of the age between 26 and 35 years (51%), with the parity of 1-3 children (55.8%) and secondary level of education (43%), while 56% were self-employed. Only 14.7% had good knowledge on SCD. The majority of the participants had ever heard of SCD (81.3%), most of them heard from the streets (42.4%), and only 2.4% heard from hospitals. Of all 600 study participants, only 2 (0.3%) knew their SCD status while 7.7% declared having a family history of SCD. A proficient level of knowledge on SCD is associated with a high level of education, occupation, and knowing personal status of SCD. Among 300 participants who were screened for SCD, 252 were Hb-AA (84%), 47 were Hb-AS (15.7%), and 1 (0.3%) was Hb-SS. Conclusion: Despite the high prevalence of hemoglobin-S among pregnant women attending antenatal clinics in urban settings in Tanzania, there is a poor level of knowledge on SCD and personal knowledge of SCD status. Maternal screening and health education on SCD should be included as part of the comprehensive package for health promotion at antenatal clinics.

Treatment and outcomes of hepatocellular carcinoma in patients with Sickle cell disease: a population-based study in the U.S.

Sickle cell disease (SCD) is a rare hemoglobinopathy which can result in chronic liver disease and cirrhosis. Patients with SCD have an increased risk of hematologic malignancy, but the prevalence of hepatocellular carcinoma (HCC) in this population is unknown. Herein, the association of SCD with HCC was examined using registry data. The SEER-Medicare database was queried to identify patients diagnosed with HCC between 2000 and 2015, and further stratified by SCD status. Propensity matching was performed to examine cancer-related survival and treatment outcomes. Overall 56,934 patients with HCC were identified, including 81 patients with SCD. Patients with SCD more frequently had cirrhosis [48.1% (39/81) vs 23.5% (13,377/56,853), p<0.01] yet presented with smaller tumors [<5cm: 51.9% (42/81) vs 38.5% (21,898/56,853), p=0.01]. After propensity matching, SCD was not associated with attenuated survival (aHR 0.73 95%CI 0.52-1.01). When stratified by treatment, patients with SCD had equivalent outcomes to chemotherapy (p=0.65), TACE/TARE (p=0.35), resection (p=0.15) and transplantation (p=0.67) when compared to non-SCD patients. This study confirms that a subset of patients with SCD will develop HCC. Importantly, therapeutic options for HCC should not be limited by pre-existing SCD, and similar survival should be expected when compared to non-SCD patients.

Influenza immunization coverage of children with sickle cell disease

ObjectivesTo assess receipt of annual flu immunization among children living with sickle cell disease (SCD). MethodsReceipt of flu immunization (2014–2019) by SCD status was assessed among all Michigan children <18 years of age using the statewide immunization registry. Logistic regression was used to estimate the odds of annual flu immunization by SCD status and age. ResultsAnnual flu immunization coverage was higher among children with SCD (46.9%; n = 751) than without (23.2%; n = 2,012,846). The annual adjusted odds of flu immunization for those with SCD were 2.8 (95% CI: 2.5–3.1) times higher than for those without SCD; there were no significant differences by age among children with SCD. Among those without SCD, adolescents aged 13–17 were 2.2 (95% CI: 2.2–2.2) times less likely to receive annual flu immunization than children 6–35 months. ConclusionsChildren with SCD had higher annual flu immunization rates than those without SCD, but >50% remain unimmunized.

Premarital genetic screening and care of Tanzanian children with sickle cell disease: a qualitative study on parents' views and experiences.

Genetic testing and counselling is one of the approaches to reduce the high birth rate of individuals with sickle cell disease (SCD). A descriptive phenomenological approach was used to explore parents' views on premarital genetic screening for sickle cell trait and their experiences in the care of Tanzanian children with SCD using a face-to-face in-depth interview. The study was conducted at sickle cell clinic at tertiary hospital in Dar es Salaam region between June and August 2020. The study found that most of the parents with SCD children knew about genetic testing and counselling after the diagnosis of their children's SCD status. Major approaches employed in managing SCD crises were supportive, preventive, and symptomatic. Parents expressed a heavy burden related to caretaking due to the lack of financial support and stigmatization. These affected their children's quality of care and management. In conclusion, participants expressed a preference for premarital genetic testing, where others insisted it becomes compulsory. In addition, there should be an adequate clinic for early screening, accessible therapeutic support and long-term follow up for children with SCD. Support to poor families with individual with SCD through national health assurance scheme and free provision of preventive medications such as hydroxyurea, is recommended.