OBJECTIVE: This study characterized caregivers\' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers\' experiences and desires for early intervention services.
METHODS: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview.
RESULTS: A total of 127 caregivers were approached, 47 participated in surveys, and 20 completed interviews. Caregivers expressed varying levels of confidence and understanding of developmental milestones across sites. Interviews highlighted three main themes: fear of SCD-related complications, variable buy-in to early intervention, and the importance of provider-caregiver relationships. While some caregivers appreciated early intervention, others questioned its necessity. Caregivers communicated interest in connecting with other families facing similar challenges, emphasizing the need for increased awareness of available resources.
CONCLUSIONS: Fear about their child\'s well-being was expressed by many caregivers, emphasizing the need for a supportive healthcare team that can help families connect with preventive interventions. While about a quarter of children had been referred to rehabilitation services, caregivers were unaware of the elevated risk for developmental delay, which diminished caregiver interest in participating in programs like early intervention. This study underscores the importance of addressing knowledge gaps and overcoming barriers to enhance care for families affected by SCD.

BACKGROUND: Sickle cell disease (SCD) is a common monogenic inheritable condition in sub-Saharan Africa. 30% of Ghanaians are estimated to be carriers creating a condition for stable SCD penetrance. Being inheritable, SCD is scientifically preventable through intentional spousal selection. This study therefore explored young adults\' knowledge, beliefs and prevention strategies regarding SCD.
METHODS: This exploratory study employed a mixed-methods approach (semi-structured questionnaires and focus group discussion [FGD]) to explore the SCD knowledge and beliefs of participants (15-49 years). The data collection was intentionally sequential; initial administration of 386 questionnaires and then followed by the FGD (16 participants). FGD was thematically analysed whereas quantitative data was explored using structural equation modeling (SEM); p < 0.05 was considered statistically significant under two-tailed assumptions.
RESULTS: Whereas 98.7% reported having heard about SCD, < 50% got the information through formal education. Overall, 49.7% knew their respective SCD status; the proportion increased with age (48.8% in < 30 years vs 64.4% in ≥ 30 years old), or higher degree status (48.8% in undergraduates vs 67.4% in postgraduates). Moreover, whereas nine-in-ten correctly identified that SCD is hereditable, three-in-ten believed that having a SCD child was a matter of fate. Our FGD revealed that whereas curses, and spiritual attack were misconceived as potential causes of SCD, stigmatization associated with SCD was a major concern. The SEM demonstrated that one\'s knowledge about SCD prevention is significantly positively associated with relationship choices (b = 0.757, p < 0.05). Also, a participant\'s knowledge about SCD preventive strategies was significantly associated with the individual\'s beliefs about SCD (b = 0.335; p < 0.05). However, a participant\'s SCD beliefs negatively mediated SCD preventive strategies-relationship choices association.
CONCLUSIONS: SCD beliefs likely transform linear quantitative associations into a complex non-linear interaction; public health campaigns ought to unearth and address SCD beliefs to maximize achieving the intended targets.

BACKGROUND: Sickle cell disease (SCD) is a prevalent genetic disorder characterized by abnormal hemoglobin formation, resulting in severe complications. Hydroxyurea (HU) therapy has demonstrated efficacy in reducing SCD-related complications; however, its utilization patterns and patient perceptions remain underexplored, particularly in the Al Ahsa region of Saudi Arabia.
OBJECTIVE: This cross-sectional study aimed to assess the prevalence of HU usage among adult patients with SCD in Al Ahsa; identify the barriers to starting, maintaining, and discontinuing HU therapy; and evaluate the patient-reported outcomes associated with its use.
METHODS: Data were collected through face-to-face surveys and medical record reviews of adult SCD patients attending outpatient clinics in the Hereditary Blood Diseases Center of Al Ahsa, Saudi Arabia, between December 2023 and March 2024. Descriptive statistics and inferential analyses were performed using SPSS version 26.
RESULTS: A total of 345 adult SCD patients were included, with a mean age of 34.12 ± 11.1 years. Most participants were male (58.6%) and unmarried (55.4%). HU utilization was reported by 57.1% of the participants, with the highest adherence observed among older age groups (p = 0.001). Significant improvements in pain severity, hospitalization rates, and quality of life were reported among HU users (p < 0.001). Common barriers to HU use included concerns about side effects, lack of medical justification, and absence of medical advice.
CONCLUSIONS: This study provides valuable insights into the utilization and perceptions of HU therapy among adults with SCD in Al Ahsa, Saudi Arabia. Addressing identified barriers and promoting patient education are crucial for optimizing therapy adherence and improving clinical outcomes in this population.

BACKGROUND: Pulmonary complications are common among children with sickle cell disease (SCD). However, there is little literature on associated lung function abnormalities in Uganda. We aimed to determine the prevalence, patterns, and factors associated with abnormal lung function among children with SCD in a tertiary care hospital in Uganda.
METHODS: A cross-sectional study was conducted among children aged 6 to 18 years at the SCD clinic (SCC) of Mulago National Super-Specialized Hospital between January 2020 and April 2021. Data on sociodemographic and clinical characteristics was collected using a standardized questionnaire. Laboratory investigations, including a complete blood count and serum lactate dehydrogenase (LDH), were done. Spirometry was performed following the ATS/ERS standards. Multivariable modified Poisson regression analysis was performed to determine factors associated with abnormal lung function.
RESULTS: A total of 332 participants were enrolled. The mean age was 11.7 ± 3.4 years, and 184 (55.4%) were female. Overall, 126 (37.9%) participants had abnormal lung function: 67/126 (53.2%) restrictive, 57/126 (45.2%) obstructive, and 2/126 (1.6%) mixed-ventilatory patterns. Factors associated with abnormal lung function were; serum LDH level > 600UL (aIRR: 1.89 95% CI: 1.2 - 7.4, p = 0.049), a history of acute chest syndrome (aIRR: 1.55, 95% CI: 1.06-2.25, p = 0.024), wasting (aIRR: 1.33, 95%CI: 1.02 - 1.72, p = 0.032), and use of charcoal for household cooking (aIRR: 1.49, 95% CI: 1.03-2.15, p = 0.035).
CONCLUSIONS: More than one-third of children with SCD in Uganda have lung function abnormalities. Strategies to improve nutrition, reduce exposure to charcoal smoke, and monitoring serum LDH levels may be important in preventing or managing abnormal lung function in this population. The identification of reversible and irreversible airway obstruction in children with sickle cell disease also highlights the need for targeted interventions to address these specific patterns of abnormal lung function.

BACKGROUND: This observational cross-sectional study aimed to identify predictors of renal complications in pediatric patients with sickle cell disease (SCD) at King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, over six months from February 2023 to July 2023. The study evaluated microalbuminuria as an early indicator of renal injury and explored its correlations with clinical and laboratory parameters and abdominal ultrasound (US) findings.
METHODS: Included were pediatric patients aged 1 to 14 years with confirmed SCD, excluding those with acute infections or pre-existing renal diseases. Data from 100 patients\' electronic medical records were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States), with a significance set at p ≤ 0.05.
RESULTS: The mean age was 7.6 ± 3.3 years, with 51 males and 49 females; 11 were diagnosed with Hb-S-beta thalassemia. Hydroxyurea (HU) compliance was high, with only four non-compliant patients, though all took folic acid. Among 42 tested for albuminuria, all had negative results (<30 mg/g creatinine). A significant association was found between SCD diagnosis and kidney, ureter, and bladder (KUB) US results (p=0.008), with abnormal KUB findings more prevalent in the Hb-S-beta thalassemia group. Patients with abnormal KUB results had significantly lower mean weight (p=0.024). Additionally, Hb-S-beta thalassemia patients had lower mean weight than hemoglobin SS (HGSS) patients (p=0.04). Though not statistically significant, Hb-S-beta thalassemia patients had higher mean systolic blood pressure (p=0.053).
CONCLUSIONS: Significant associations were identified between SCD diagnosis type and renal US results, with lower body weight emerging as a potential predictor of renal complications. High HU compliance and its impact on renal outcomes warrant further investigation. Routine monitoring of microalbuminuria and KUB US may aid early detection of renal complications in pediatric SCD patients. Further studies with larger sample sizes are recommended to validate these findings and develop comprehensive renal protective strategies.

UNASSIGNED: Estrogen-containing hormonal contraception (HC) is a well-established risk factor for venous thromboembolism (VTE). Women with sickle cell disease (SCD) also have an increased risk of VTE. However, it is unknown if exposure to HC exacerbates the risk of VTE in women with SCD.
UNASSIGNED: Assess the impact of HC on VTE risk in women with SCD and explore additional risk factors contributing to VTE development.
UNASSIGNED: We analyzed a retrospective cohort of women of reproductive age (15-49 years) with SCD at the University of North Carolina from 2010 to 2022.
UNASSIGNED: We identified 370 women with SCD, and 93 (25.1%) had a history of VTE. Among 219 women exposed to HC, 38 of 184 (20.6%) had a VTE while actively using HC, whereas 20 of 151 (13.2%) women never exposed to HC had a VTE. Of the patients exposed to HC, 64 of 184 (34.7%) were on estrogen-containing HC, with 120 of 184 (65.3%) using progestin-only formulations. Cox regression analysis found that progestin-only formulations increased VTE risk (hazard ratio: 2.03; 95% CI: 1.107-3.726, P < .05). However, when accounting for disease severity, the association between progestin-only treatment and VTE risk was not significant. Indeed, a nuanced analysis revealed that both severe (odds ratio: 11.79; 95% CI: 5.14-27.06; P < .001) and moderate (odds ratio: 4.37; 95% CI: 1.77-10.76; P = .001) disease increased risk compared with mild disease. Neither genotype nor hydroxyurea use influenced VTE risk.
UNASSIGNED: Overall, we found that increased thrombotic risk is more likely influenced by disease status than HC exposure and should play a role in shared decision-making with patients.

UNASSIGNED: Co-existing iron deficiency in patients of sickle cell disease (SCD) and trait may worsen anemia, and adversely affect neuro-cognitive development and growth. Determining a cut-off below which Mean corpuscular Volume (MCV) can predict iron deficiency in SCD patients can preclude use of more expensive test serum ferritin.
UNASSIGNED: This study was conducted to determine the diagnostic accuracy of low MCV in detecting iron deficiency compared to serum ferritin levels in patients with SCD.
UNASSIGNED: 60 consecutive patients with SS or AS pattern on hemoglobin electrophoresis were enrolled. The index test (MCV) and the reference standard test (serum ferritin) were performed in a blind and independent manner. The measures of diagnostic accuracy were calculated and the precision of the point estimates were expressed by 95% confidence intervals. As MCV is a continuous variable, we also used multi-level likelihood ratios to compute diagnostic accuracy of MCV at several cut-points.
UNASSIGNED: The sensitivity of low MCV in detecting iron deficiency was 40.0% (95% CI-20.0-63.6), the specificity was 78.4% (95% CI-61.3-89.6) using serum ferritin as a reference standard. The sensitivity and specificity of predicting coexisting iron deficiency at this point was 60.9% (CI-38.6-80.3%) and 75.7% (CI-58.8-88.2%) respectively.
UNASSIGNED: The low sensitivity (40%) of microcytosis in detecting iron deficiency indicates that many cases will be missed if MCV alone is used to detect co-existing iron deficiency anemia in SCD patients. No single test is good enough to detect co-existing iron deficiency and a combination of tests might be useful.

UNASSIGNED: Due to the numerous complications associated with sickle cell disease (SCD), patients often receive a variety of medications alongside their SCD treatment. However, a notable gap exists in the current literature regarding medication use patterns among them. This study aimed to investigate medication usage patterns in patients with SCD.
UNASSIGNED: This cross-sectional study, conducted in Bushehr Province, employed a stratified random sampling method to select eligible participants with SCD. A thorough interview gathered various information, including details about the medications. The Anatomical Therapeutic Chemical classification system was utilized for drug classification. Polypharmacy was defined as the concurrent use of at least five medications.
UNASSIGNED: A total of 300 individuals with SCD were included in this study. Polypharmacy was observed in 26.3% (95% CI: 20.8%-32.8%) of the study population. The analyses revealed positive associations between the use of more concurrent medication use and higher age groups and having multimorbidity. Antianemic preparations (86.7%), antineoplastic agents (58.3%), and vitamins (41.0%) were the most frequent medication classes used by the study participants.
UNASSIGNED: Our study revealed notable underutilization of hydroxyurea and a high rate of polypharmacy, associated with age and multimorbidity, among patients with SCD in southern Iran.

OBJECTIVE: To determine if differences exist in the risk of developing large vessel retinal vascular occlusions in patients with sickle cell states.
METHODS: Retrospective cohort study.
METHODS: Patients with sickle cell disease (SCD) or trait evaluated by an ophthalmologist were compared with matched controls without SCD or sickle cell trait (SCT) also evaluated by an ophthalmologist.
METHODS: This study used deidentified data from a national database (2006-2024), using International Classification of Diseases 10 codes to select for retinal vascular occlusions. Propensity score matching was performed with respect to age, sex, race, ethnicity, smoking, hypertension, diabetes, dyslipidemias, and obesity, resulting in hemoglobin SS (HbSS), hemoglobin SC (HbSC), and SCT cohorts and matched control cohorts.
METHODS: Risk ratios (RRs) and 95% confidence intervals (CIs) of retinal vascular occlusion diagnosis, including central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), central retinal vein occlusion, branch retinal vein occlusion, and corneal dystrophy as a negative control, given SCD or SCT.
RESULTS: After propensity score matching, HbSS (n = 10 802; mean age ± standard deviation, 38.6 ± 20.6 years), HbSC (n = 4296, 34.3 ± 17.8 years), and SCT (n = 15 249, 39.8 ± 23.7 years) cohorts were compared with control cohorts (n = 10 802, 38.7 ± 20.7 years; n = 4296, 34.6 ± 18.0 years; n = 15 249, 39.9 ± 23.8 years, respectively). Patients with SCD (HbSS) had higher risk of developing any retinal vascular occlusion (RR, 2.33; 95% CI, 1.82-3.00), CRAO (RR, 2.71; 95% CI, 1.65-4.47), and BRAO (RR, 4.90; 95% CI, 2.48-9.67) than matched controls. Patients with HbSC disease had higher risk (RR, 3.14; 95% CI, 1.95-5.06) of developing any retinal vascular occlusion than matched controls without SCD. Patients with SCT did not have higher risk of developing retinal vascular occlusions (RR, 1.01; 95% CI, 0.81-1.26) than matched controls.
CONCLUSIONS: In a retrospective cohort study, patients with HbSS SCD have an increased risk of developing retinal vascular occlusions, and more specifically CRAO and BRAO, compared with patients without SCD.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.