Hydroxyurea Utilization Research Articles

Utilization and Perceptions of Hydroxyurea Therapy Among Adult Patients With Sickle Cell Disease in Al Ahsa, Saudi Arabia: A Cross-Sectional Study.

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. 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. 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. 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. This study provides valuable insights into theutilization and perceptions of HU therapy among adults with SCDin Al Ahsa, Saudi Arabia. Addressing identified barriers and promoting patient education are crucial for optimizing therapy adherence and improving clinical outcomes in this population.

Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study.

In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several countries in sub-Saharan Africa. This study examined patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, in Uganda. To understand the patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease, we conducted a parallel convergent mixed methods study at outpatient departments of two national referral hospitals in Uganda from October 2022 to January 2023. The cross-sectional mixed-methods study employed both quantitative and qualitative methods. We collected survey data from a systematic sample of 259 participants and conducted individual interviews with a purposive sample of 40 participants (20 adolescents or their caregivers and 20 adult patients with SCD) and interviewed them individually on their knowledge, perceptions, barriers, and facilitators of HU utilization. Descriptive data were analyzed using Stata 16, whereas qualitative data were analyzed thematically using an inductive approach supported by NVivo 12 software. We triangulated data to determine the concordance of qualitative and quantitative data. The study enrolled 40 participants for qualitative interviews and 259 patients for quantitative, with an average age of 16, over half being female, 46% having secondary education, and 96% unmarried. The prevalence of HU use was 78%. The study identified three themes as follows: Patient barriers at the individual including Inadequate knowledge about HU, Persistent pain, Poor adherence to HU, Poor communication with health care workers, and Psychosocial and emotional challenges. At the facility level, long queues and poor quality of care, drug-related side effects that affect HU, and drug stock-outs were reported. Myths, rumors, and misconceptions about HU, and gender-related barriers were reported to affect HU utilization at a community level. Facilitators for the use of HU and recommendations for improvement. Facilitators included perceived benefits, long duration on HU, information sharing by healthcare workers, availability of complementary drugs, confirmation of diagnosis, and availability of medication at public health facilities or private pharmacies. Patients suggested continuous adherence support, encouragement from healthcare workers, sensitization about benefits and risks, a peer-to-peer approach, and financial support for adolescents and women to start businesses to resolve financial problems. Implementing the use of HU has been challenging in Uganda and needs improvement. Facilitators to hydroxyurea use have been highlighted, though Patient-identified barriers at individual, facility, and community levels that need to be resolved. The experiences and insights shared by our participants provide invaluable guidance for increasing the uptake of HU. Further studies are needed to establish validated instruments to assess patients' pain communication and adherence to the HU regimen.

Clinical Practice Patterns in Sickle Cell Disease Treatment: Disease-modifying and Potentially Curative Therapies.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSβ 0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management.

Recruitment Strategies in the Integration of Mobile Health Into Sickle Cell Disease Care to Increase Hydroxyurea Utilization Study (meSH): Multicenter Survey Study.

Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. Recruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. Total enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P<.001). We found that timely adaptation in recruitment strategies secured high recruitment rates using an assortment of enriched remote recruitment strategies. Flexibility in approach and reducing the burden of enrollment procedures for participants aided enrollment. It is important to continue identifying effective recruitment strategies in studies involving patients with SCD and their providers and the impact and navigation of recruitment challenges. ClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351. RR2-10.2196/16319.

High hydroxyurea usage in sickle cell anemia regardless of patient demographics.

Hydroxyurea is highly effective in sickle cell disease, but it is still underutilized. Reports of hydroxyurea utilization largely use Medicaid data, and socioeconomics is often cited as a barrier. To address whether patient demographics influenced the high hydroxyurea usage rate recently reported for the pediatric sickle cell program of Northern Virginia, analysis of data from 2011 to 2021 revealed no statistical difference in hydroxyurea usage rate between Medicaid and non-Medicaid, African American and African, or age less than 13 and age greater than or equal to 13years cohorts, demonstrating that hydroxyurea can be successfully implemented across demographic groups.

High Hydroxyurea Usage in Sickle Cell Anemia Regardless of Patient Demographic

Introduction/Background: Hydroxyurea is highly effective in sickle cell disease, yet it is still underutilized. The Pediatric Sickle Cell Program of Northern Virginia recently published a 10-year analysis of uniform hydroxyurea (HU) implementation starting in infancy for all patients with sickle cell disease of severe genotype (SCA), demonstrating rise in HU usage from 32.5% baseline rate to 79.6% after two years, and to &amp;gt; 90% after 8 years. 1 Other HU utilization studies reporting lower rates largely use Medicaid data, and lower socioeconomics is often cited as a barrier to HU utilization. The Northern Virginia study reported on all patients with SCA regardless of insurance coverage, thus raising the question whether the high HU usage rate achieved in this program was influenced by a high proportion of non-Medicaid patients or other unusual demographic features. Therefore, we analyzed 10 years of HU usage data by insurance, ethnicity, and age. Methods: HUdata extracted from a longitudinal REDCap database and electronic medical records (EMR) with IRB approval (Children's National Medical Center IRB, Pro00002745, Pro00013374) previously reported 1 for five 2-year intervals are additionally analyzed for insurance, ethnicity, and age, with new data for 2019-2021. HU-eligibility includes SCA patients age ≥ 9 months and not chronically transfused. HU users (on HU) are patients demonstrating Hgb F rise and expected hemogram changes in response to HU, monitored every 2-3 months; HU non-users (not on HU) are patients who refuse HU or are grossly non-adherent as evidenced by lack of changes in Hgb F and hemogram. Pharmacy dispense records available in Epic EMR are used as corroborative information. Results: 1. Medicaid patients comprised 39 - 46% and non-Medicaid patients comprised 54 - 61% of all patients over the five 2-year periods. African-American (AA) and African patients comprised 85% of all patients. Medicaid coverage ranged from 24 - 39% for AA patients and 38 - 48% for African patients. (African is defined as born in Africa or having parents born in Africa who immigrated to the US.) 2. Comparing HU usage by insurance over the five 2-year periods, HU users increased from 72% to 91% for Medicaid patients and from 83% to 95% for non-Medicaid patients. Conversely, HU non-users decreased from 28% to 9% for Medicaid patients and from 17% to 5% for non-Medicaid patients. No statistical difference was detected in HU usage by Medicaid versus non-Medicaid insurance in any interval (p = 0.13 to 0.91) (Table 1). 3. HU usage rates in AA and African patients were not statistically different (p = 0.07 to 0.32), except in one interval (2013-15) (p = 0.006) (Table 1). 4. Comparison of HU usage in two age groups, 9 months-12 years and ≥ 13 years, showed that while HU non-acceptance/non-adherence tended to be higher in the age ≥ 13 group, no statistical significance was reached in any interval (p = 0.13 to 0.97) (Table 1). 5. The uniform HU implementation program targeted for fetal hemoglobin (Hgb F) 30% or higher by frequent HU dose optimization and close adherence monitoring. Hgb F &amp;gt; 20% was considered good adherence, and Hgb F 10-20% reflected partial adherence. Partially adherent patients did not distribute differently between Medicaid and non-Medicaid insurance (p = 0.07 to 0.86) but were predominantly age &amp;gt; 13 (p = 0.0005 to 0.001) (Table 2). Conclusion: 1. HU users and HU non-users did not disproportionately distribute to any demographic group. 2. Uniform HU implementation was effective in both Medicaid and non-Medicaid populations. 3. Ethnicity and age were not significant factors in HU uptake or acceptance, but decreased HU adherence is more frequent in teenagers. 4. HU can be effectively implemented for all SCA patients across demographic groups. Medicaid insurance, as a proxy for socioeconomic level, is not a barrier to high HU usage. Reference: 1. Phan V, Park JA, Dulman R, Lewis A, Briere N, Notarangelo B, Yang E. Ten-year longitudinal analysis of hydroxyurea implementation in a pediatric sickle cell program. Eur J Haematol. 2022 Nov;109(5):465-473. doi: 10.1111/ejh.13827. Epub 2022 Sep 2. PMID: 35811388.

Addressing Provider-Dependent Gaps in Sickle Cell Disease Care

Sickle cell disease (SCD) affects around 100,000 Americans and presents numerous health-related challenges thus necessitating effective management strategies. Educational initiatives on evidence-based intervention are known to play a crucial role in improving patient-related outcomes (PRO) and enhancing the quality of life (QOL) for individuals with SCD. Community-based hospitals face challenges in managing SCD patients. Patients who are unaffiliated with a comprehensive sickle cell center have increased healthcare utilization, readmissions, and patient dissatisfaction due to limited access to specialized services and discrepancies in care delivery. Addressing these disparities and expanding access to care is crucial in optimizing SCD management. The purpose of this exploratory observational study was to identify provider-related gaps in a community-based tertiary center. The survey assessed internal medicine trainees' and hospitalists' baseline knowledge and comfort level at a tertiary care center with a total of 304 yearly adult admissions related to SCD management. The survey was distributed through an online platform. Data was analyzed to identify trends and gaps in internal medicine providers. Our survey had a total of 30 respondents, the response rate was 39%. Most respondents (90%) had prior experience with SCD patients; however, many gaps were identified [Table 1]. 70-75% of physicians felt comfortable managing acute pain and chronic illnesses, yet only half of these providers were comfortable with managing SCD patients. While our study sample is small, similar results were noted in a study conducted in another community-based hospital in the Chicagoland area. Our study shows a similar provider-related gap in SCD care delivery. Dr. Kanter proposed a model of care delivery which is known as the “hub and spoke” model. It offers a promising solution, creating a networked system of care with a central hub and secondary spokes providing more limited services. Community-based hospital settings can serve as spokes, bringing specialized SCD care closer to patients in local areas. Hence, we propose that this model can be further modified to include provider education. This equips non-sickle cell specialists at various spokes with the necessary knowledge and skills through targeted education by sickle cell specialists at a centralized hub. Targeting provider gaps may significantly improve PRO. Our residency program hopes to establish an affiliation with the University of Illinois (UI) Health Sickle Cell Center (SCC) to help with educating trainees on SCD. The UI Health SCC was one of eight sites participating in the National Sickle Cell Disease Implementation Consortium (SCDIC) with the goal of helping patients access longitudinal care, increase hydroxyurea utilization when appropriate, and provide proper pain management in ED. They are also part of the Recruitment and Engagement in Care to Impact Practice Enhancement (RECIPE) project which focuses on patients with SCD that are unaffiliated with care centers and attempts to understand and eliminate their barriers to care. Future efforts should include implementing targeted provider education, within the context of a hub and spoke model. This may help bridge the gap in care delivery and ultimately enhance outcomes for SCD patients.

Socioeconomic Status and Risk of Stroke As Assessed By Transcranial Doppler: A Displace Study Secondary Analysis

Background: Transcranial doppler (TCD) screening (Sickle Stroke Screening) identifies children ages 2-16 years with sickle cell disease (SCD) at an increased risk for stroke. Significant barriers to undergoing annual screening exist for patients with SCD. Previous studies have shown that individuals from households on public insurance with limited neighborhood opportunity have increased barriers to receiving adequate healthcare, including routine screening; however it is unknown whether low socioeconomic status (SES) influences TCD results. Methods: We conducted a secondary analysis of the DISPLACE study, which included a cohort of 3243 TCD-eligible individuals aged 2-16 who had at least one TCD screen performed during their year of study enrollment. We utilized insurance type (Medicaid/CHIP or public versus all other insurances) and overall childhood opportunity index (COI) group (Very Low versus all other COI levels [Low, Medium, High, and Very High]) to proxy household- and neighborhood-level SES. We then examined the association between household- and neighborhood-level SES and conditional and/or abnormal TCD screening results. Baseline characteristics of the overall cohort (Table 1) were described by COI group and insurance type. The primary outcome was TCD result at baseline (i.e. a patient's first TCD in the database); categorized as abnormal, high-conditional, and normal (reference group). Multinomial logistic regression analysis was used to assess whether clinical (age, sex [female vs. male], hemoglobin (Hgb) level, white blood cell [WBC] count, presence of clinical hypertension [yes, no], hydroxyurea (HU) prescription at baseline [yes, no]) or socioeconomic factors (insurance type and COI group) were independently associated with TCD result. The multinomial regression accounted for age, Hgb level, WBC count, HU prescription, COI group, and insurance type. All tests were two-tailed and, an alpha level of &amp;lt;0.05 and &amp;lt;0.1 (to reduce type II error in logistic regression) were used to determine statistical significance. Results: The analytic cohort included 3243 children (Table 1), with 1346 (41.5%) children living in Very Low COI neighborhoods and 2180 (67.2%) of households with public insurance. HU was prescribed to 60.7% of individuals, and this varied by COI level (p=0.021), but not insurance type (p=0.758). WBC count was significantly higher in the Very Low COI group (p=0.004) and public insurance group (p&amp;lt;0.001). Hgb level was noted to be significantly lower in the Very Low COI (p=0.031) and public insurance (p&amp;lt;0.001) groups. Bivariate logistic regression analysis revealed that COI group (OR 1.53, p=0.08) and insurance type (OR=1.76, p=0.056) were significantly associated at p&amp;lt;0.1 with abnormal TCD outcome individually. Lack of HU prescription was significantly associated at p&amp;lt;0.05 with abnormal TCD result (Odds Ratio [OR]=20.36, p&amp;lt;0.001), and WBC count (OR=1.05, p=0.055) was significantly associated at p&amp;lt;0.1 with abnormal TCD result individually. In the multinomial logistic regression model (included variables listed above), only lack of HU prescription remained significantly associated at p&amp;lt;0.05 with abnormal TCD result (OR=19.09, p&amp;lt;0.001). Conclusion: The most robust predictive factor determining abnormal or conditional TCD status in this cohort was lack of HU prescription. Public insurance and COI group as proxies for SES were not independently associated with abnormal or conditional TCD results. As such, the disparities seen by individuals from proxied lower SES are likely mediated by utilization of HU. Notably, HU prescription rates differed by COI group, but not insurance type, suggesting possible neighborhood level factors (such as availability of pharmacies dispensing HU) influencing HU prescription that wouldn't be reflected by insurance type. The limitations of using socioeconomic proxies such as COI group and insurance type must be noted, as these proxies assign group characteristics to an individual based on a snapshot in time, which may not be representative of the dynamic nature of one's SES. Nevertheless, these findings highlight the need to better understand the possible association between SES and HU prescription, as limited HU access and utilization could result in significant health disparities in both treatment and outcomes.

Frequency of Painful Crisis and Other Associated Complications of Sickle Cell Anemia Among Children.

Background Sickle cell disease (SCD) represents a group of inherited health conditions that affect red blood cells. SCD is a relatively common genetic disorder in Saudi Arabia, with the highest prevalence found in the Eastern Province region. The most common complications of SCD include acute chest syndrome, vaso-occlusive crisis, stroke, and avascular necrosis of the femoral head. The disease itself isnota cause of mortality but systemic complications are. Methodology In this retrospective study, we aimed to determine the frequency of painful crisis and the associated complications of sickle cell anemia (SCA) among children at King Saud Medical City (KSMC) in Riyadh, Saudi Arabia. Results This study included a total of 70 children with SCA below the age of 14 years who were admitted to KSMC from January 2021 to December 2021. Overall, 60% of the participants had one painful crisis attack per year, whereas 27% had two attacks. Furthermore, 94% of the participants were being treated with hydroxyurea. The most frequent cause of admission was painful crises with acute chest syndrome. Conclusions This study highlights the frequency of hydroxyurea use among SCA patients. Our results showed that participants who developed one to two painful crises per year were hospitalized for four to nine days on average with increased utilization of hydroxyurea.

Evaluating the implementation of a multi-level mHealth study to improve hydroxyurea utilization in sickle cell disease.

Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the intervention implementation. In this report, we describe engagement with stakeholders, planning of the implementation process, and final analytical plan to evaluate the implementation outcomes. During 19 meetings, a 16-member multidisciplinary SCDIC implementation team created, conceived, and implemented a project that utilized Intervention Mapping to guide designing an intervention and its evaluation plan. The process included five steps: (1) needs assessment of low hydroxyurea utilization, (2) conceptual framework development, (3) intervention design process, (4) selection of models and frameworks, and (5) designing evaluation of the intervention implementation. Behavioral theories guided the needs assessment and the design of the multi-level mHealth intervention. In designing the evaluation approach, we combined two implementation frameworks to best account for the contextual complexity at the organizational, provider, and patient levels: (1) the Consolidated Framework for Implementation Research (CFIR) that details barriers and facilitators to implementing the mHealth intervention at multiple levels (users, organization, intervention characteristics, broader community), and (2) the Technology Acceptance Model (TAM), a conceptual model specific for explaining the intent to use new information technology (including mHealth). The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework was used to measure the outcomes. Our research project can serve as a case study of a potential approach to combining different models/frameworks to help organize and plan the evaluation of interventions to increase medication adherence. The description of our process may serve as a blueprint for future studies developing and testing new strategies to foster evidence-based treatments for individuals living with SCD.

Hydroxyurea utilization and dose optimization in children with sickle cell disease (SCD)

Hydroxyurea utilization and dose optimization in children with sickle cell disease (SCD)

Outcomes of Hydroxyurea Accessed via Various Means and Barriers Affecting Its Usage Among Children with Sickle Cell Anaemia in North-Western Tanzania.

To assess clinical and haematological outcomes of Hydroxyurea accessed via various access means and uncover the barriers to its utilization in children with Sickle cell anaemia (SCA), North-western Tanzania. A retrospective study was conducted between October 2020 and April 2021 at Bugando Medical Centre (BMC) through review of medical files to compare the clinical and haematological outcomes among children with SCA at baseline and followed up retrospectively for at least one year of hydroxyurea utilization, accessed via cash, insurance and projects. Subsequently, a cross-sectional survey was conducted among parents and caregivers to ascertain the barriers to access of hydroxyurea via the various means. The p-values <0.05 were considered statistically significant. We identified 87 children with SCA who were on hydroxyurea for at least one year. The median age at baseline (before hydroxyurea) was 99 [78-151] months, and 52/87 (59.8%) were male. Compared to baseline, there was a significant reduction in proportion of patients reporting vaso-occlusive crisis, admissions and blood transfusions, a significant increase in Haemoglobin and mean corpuscular volume, conversely a significant reduction in absolute neutrophil and reticulocytes to both insurance and project participants. There was no significant change in most of these parameters among patients who accessed hydroxyurea via cash. Further, a total of 24/87 (27.6%) participants reported different barriers to access of hydroxyurea, where 10/24 (41.7%) reported hydroxyurea to be very expensive, 10/24 (41.7%) reported insurance challenges, and 4/21 (16.6%) reported unavailability of the drug. The paediatric patients utilizing hydroxyurea accessed via insurance and projects, but not cash, experienced significant improvement in the clinical and haematological outcomes. Several barriers for access to hydroxyurea were observed which appeared to impact these outcomes. These findings call for concerted efforts to improve the sustainable access to hydroxyurea among all patients with SCA.

The Next Step in Telehealth Education in a Low-Income Setting: Implementing a Project Echo for Sickle Cell Disease

Background and Aims: Sickle Cell Disease affects nearly 100 million people worldwide and disease complications are responsible for over 50% of deaths among those affected with the most severe form. It is estimated that each year, over 300,000 children are born annually with this disease and over 70% of these births occur in Sub-Saharan Africa. In Kenya, approximately 14,000 children are born with Sickle Cell Disease each year with a greater incidence in malaria endemic areas including lake-region, western, and coastal regions. Advances have been made in the United States to reduce the disease related mortality at 5 years of age to 3%. However, in developing countries of Sub-Saharan Africa, this number is greater than 50%. Since 2011, hematologists from North American institutions have partnered with Kenyan specialists to deliver educational seminars in African counties with a high incidence of Sickle Cell Disease. As an expansion of these efforts, a telehealth educational platform has been developed, capable of providing ongoing collaboration and mentorship for high risk communities. Methods: The combined team of Kenyans and North American providers collaborated to launch a Project ECHO program focusing on Sickle Cell Disease. The virtual educational platform - a hub and spokes teaching model - was implemented based on previous success with other chronic diseases in the region. A complete panel of experts consisting of pediatric and adult hematologists from Kenya and the United States, nursing leadership, patient advocates, social workers, and local physician leaders was assembled as the hub team. Recruitment for the ECHO began in April 2022 in Western Kenya and consisted of participants from prior educational workshops and participants from other ECHO programs at county referral hospitals. A curriculum was built focusing on infant screening, infection prevention, and utilization of Hydroxyurea, with expanding topics based on community needs. The ECHO program occurred at monthly intervals utilizing the Zoom platform. The sessions consisted of both a scheduled didactic and a case-based discussion. The didactic was given by a Kenyan expert while the cases were submitted by ECHO participants from the community. Attendance was tracked by the ECHO platform automatically including recurrent attendance and participant county. Surveys were utilized on a semi-annual basis to further assess educational impact. Results: The program launched in June 2022 with initial success. Participation at early sessions averaged 60 attendees with participants attending from 24 of the 47 total counties in Kenya. ECHO leadership maintained fidelity to the model with an emphasis on dialogue, collaboration, and mentorship. The ECHO community has also flourished outside of the virtual sessions as evidenced by increased dialogue amongst participants via electronic messaging and an increase in Sickle Cell Disease referral patterns. Conclusions: Significant morbidity and mortality persists for sickle cell disease in low- and middle-income countries such as Kenya and education at the community level is a key mechanism to address these disparities. The utilization of a telehealth education program such as Project ECHO represents a strong mechanism to continue building local, regional, and international partnerships to improve care together.

Association of Community-Level Socioeconomic Distress with Nutritional Status in People with Sickle Cell Anemia

Introduction: Sickle cell anemia (SCA) is characterized by a myriad of acute and chronic complications. These complications negatively impact the ability to achieve educational and occupational goals making this group a particularly vulnerable population to socioeconomic challenges (PMID 30540112). Furthermore, most patients with SCA in the U.S. are Black and are disproportionately affected by socioeconomic inequity due to the historical effects of systemic racism (PMCID: PMC4817358). In the general population, indices of socioeconomic distress are associated with poor nutrition (PMID 25573510). Patients with SCA also experience a high frequency of food insecurity (PMID 34811867). The association of community-level socioeconomic distress with nutritional status in people with SCA is unknown. Methods: We conducted a cross-sectional study to describe the burden of community-level socioeconomic distress and its impact on nutritional status in an SCA cohort (n=332) treated at an urban academic institution. The distressed community index (DCI), a composite of socioeconomic indicators (including no high school diploma, housing vacancy rate, adults not working, poverty rate, median income ratio, and changes in employment and establishments) that estimate the economic well-being of a community, was determined for each individual patient's residential address using 2014-2018 U.S. Census Bureau's American Community Survey and the Business Patterns database. DCI score ranges from 0-100 with a higher score indicating a more distressed community. The association of DCI with measures of nutritional status (serum albumin, body mass index [BMI], vitamin D 25-OH) and hemoglobin concentration were determined using linear regression. The analyses were adjusted for age, sex, and hydroxyurea use. The beta coefficients provided are based on increments of 10 for DCI. Median and interquartile ranges (IQR) are provided. Results: The median age of the cohort was 31 years (IQR, 24-41 years), 55% were female, 53% were on hydroxyurea therapy, and the median BMI was 23 kg/m2 (IQR, 21-26 kg/m2). The median DCI in this cohort was 87 (IQR, 61-96) with 61% of SCA patients living in a distressed tier (DCI≥ 80) and only 5% living in a prosperous tier (DCI< 20). A higher DCI, reflecting an increase in socioeconomic distress, was associated with a trend for a lower odds ratio (OR) of being on hydroxyurea therapy (OR 0.93; 95% CI 0.86-1.0). An increasing DCI was significantly associated with lower serum albumin (β= -0.02; P=0.016), BMI (β= -0.01; P=0.045), and vitamin D 25-OH levels (β= -0.7; P=0.001), adjusting for age, sex, and hydroxyurea use (Figure). Furthermore, SCA patients living in a more distressed community had a trend for lower hemoglobin concentrations (β= -0.05; P=0.077) with similar adjustments. Discussion: In conclusion, we demonstrate that a high proportion of patients with SCA treated at an urban academic institution live in distressed socioeconomic communities. Higher distressed community indices are associated with lower utilization of hydroxyurea and lower measures of nutritional status. Future studies investigating the effects of socioeconomic distress on access to outpatient care and healthy foods may guide public health strategies to improve health disparities in the SCA population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Understanding Hydroxyurea Utilization in Sickle Cell Disease: Exploring Patient and Provider Attitudes and Beliefs

Introduction Hydroxyurea (HU), a first line sickle cell disease (SCD) modifying drug, has a 22%-48% utilization rate, according to national estimates (Lanzkron 2006, Stettler 2015, Knisely 2020). There are numerous factors identified as barriers to adherence of hydroxyurea such as access to care (Badawy 2017). Given the high frequency of SCD inpatient admissions at the University of Chicago Medical Center (UCMC) and thus the limited opportunity for outpatient care where disease modifying therapies can be initiated, we proposed a quality improvement project to monitor HU education and usage during inpatient encounters. Methods Our project was reviewed by the UCMC Institutional Review Board and approved to meet quality improvement (QI) determination. To address the question of HU initiation in SCD during inpatient encounters, we surveyed key stakeholders including patients with SCD and providers. We identified consecutive patients with SCD who were either established with primary care or hematology at UCMC (n=197) and distributed our deidentified survey through a REDCap secure link to patients with active email accounts (n=135). We designed a provider survey eliciting knowledge, beliefs, and perspectives on HU use in SCD and distributed this through REDCap to 182 frontline providers. We analyzed the data qualitatively, identifying patterns and common themes from aggregate responses and free text answers. Results The patient survey response rate was 31% (n=42/135). Forty-five percent (n=18) of patients agreed that they missed follow up appointments due to admissions. Approximately half of patient respondents indicated they were not taking HU (n=19). Additionally, of those patients, 72% (n=14) indicated they would be willing to deal with the side effects of HU if it improved their SCD symptoms and 32% (n=6) said they would consider initiation of HU during an inpatient encounter. Patient respondents cited the benefits of HU, including improving quality of life (33%; n=13), preventing pain episodes (43%; n=17), improving mortality (18%; n=7), and helping prevent hospitalizations (36%; n=14). In terms of further education, 35% (n=14) of patient respondents indicated they would like to learn more about HU. 88% (n=35) indicated they would like to learn more about other disease modifying therapies. The provider survey response rate was 73% (n=132/182), of whom, 40% (n=52) were IM or Med/Peds residents, 28% (n=37) were medicine attendings, and 11% (n=15) were Hematology/Oncology faculty or fellows. 98% (n=129) of respondents overall agreed that HU initiation should be offered to patients with SCD during inpatient encounters and that the benefits of HU in SCD outweighed the potential harms. Providers requested tools to facilitate prescribing HU during inpatient encounters, including bundled orders ("orderset") within the EMR (55%; n=73), an option for inpatient SCD consult services (28%; n=37), education sessions and materials (45%; n=59), and a linked outpatient hematology referral system (58%; n=77). Conclusion: Results from our patient survey demonstrate an unmet need for expanding access to HU into inpatient encounters and providing access to other disease modifying therapies and potential cures. Providers would be comfortable with initiation and monitoring of HU during inpatient SCD encounters. To facilitate this, providers request additional education and process resources. Results from both surveys inform a plan to address disparities in HU utilization rates among patients with SCD at UCMC, in addition to providing opportunities to enhance SCD care overall. The path forward will include building curricula for providers, educational handouts on disease modifying therapies for patients, generating a HU prescribing orderset embedded in the EMR, and innovating a SCD inpatient consult service at UCMC.

Utilization of Hydroxyurea Among Patients Diagnosed with Sickle Cell Disease in Jazan, Saudi Arabia.

The early diagnosis of sickle cell disease (SCD) patients and getting appropriate treatment are crucial for improving clinical outcomes. This study aims to assess the use of hydroxyurea among patients diagnosed with SCD and assess factors influencing the attitude toward the medication and the reasons for discontinuation. This study was a cross-sectional investigation targeting parents or caregivers of children diagnosed with SCD in the Jazan region of Saudi Arabia. Data were collected from tertiary healthcare hospitals via a self-administered questionnaire. The questionnaire was composed of sections measuring the participants' demographics, the number of children diagnosed with SCD, the use of hydroxyurea, and the parents' beliefs about hydroxyurea. There were 301 parents or caregivers recruited. The majority of the recruited participants were mothers (54.5%), and nearly half of the sample were older than 35. More than 80% of the participants declare that one or more of their children are receiving hydroxyurea to manage SCD. The majority of participants declared that using hydroxyurea reduced the frequency of body pain episodes, emergency department visits, and hospital admissions. Participants' major concern about the use of hydroxyurea was related to the fear of weakening their immunity (29.5%) and hydroxyurea's perceived effect on fertility (16.8%). Furthermore, 52 (18%) of the participants declared that the use of hydroxyurea to manage the disease was stopped; the main reasons for stopping was their belief that hydroxyurea had side effects and its impact on weakening of their immune system. The findings indicate the importance of increasing the role of clinicians in educating patients and caregivers about the use of hydroxyurea and its benefits.

Primary Prevention of Stroke in Children With Sickle Cell Anemia in Nigeria: Protocol for a Mixed Methods Implementation Study in a Community Hospital.

BackgroundIn Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in Nigeria (1R01NS094041: SPRING), TCD screening was adopted as standard care at Barau Dikko Teaching Hospital in Kaduna. However, with just 70 radiologists and only 3 certified in TCD screening in the state, just 5.49% (1101/20,040) of eligible children with SCA were screened. Thus, there is a need to explore alternate implementation strategies to ensure children with SCA receive standard care TCD screening to decrease stroke incidence.ObjectiveThis protocol describes a study to create a stroke prevention program in a community hospital in Kaduna through task shifting TCD screening to nurses and training medical officers to initiate and monitor HU utilization for stroke prevention.MethodsThis study will be conducted at 2 sites (teaching hospital and community hospital) over a period of 3 years (November 2020 to November 2023), in 3 phases using both quasi-experimental and effectiveness-implementation study designs. In the needs assessment phase, focus groups and structured interviews will be conducted with health care providers and hospital administrators to identify barriers and facilitators to evidence-based stroke prevention practices. Results from the needs assessment will inform intervention strategies and a process plan to fit the needs of the community hospital. In the capacity building phase, nurses and medical officers at the community hospital will be trained on TCD screening and HU initiation and monitoring. In the implementation phase, children with SCA aged 2-16 years will be recruited into a nonrandomized single-arm prospective trial to determine the feasibility of initiating a task-shifted stroke prevention program by recording recruitment, retention, and adherence rates. The Reach and Effectiveness components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework will be used to evaluate implementation outcomes between the community and teaching hospitals.ResultsThe needs assessment phase of the study was completed in February 2021. Manuscript on findings is currently in preparation. Capacity building is ongoing with TCD training and sickle cell disease and stroke education sessions for nurses and doctors in the community hospital. Recruitment for the implementation trial is expected to commence in July 2022.ConclusionsThis study proposes a structured, theory-driven approach to create a stroke prevention program in a community hospital in Kaduna, Nigeria, to decrease stroke incidence among children with SCA. Results will provide preliminary data for a definitive randomized clinical trial in implementation science.International Registered Report Identifier (IRRID)PRR1-10.2196/37927

Promoting access of hydroxyurea to sickle cell disease individuals: Time to make it an essential medicine.

Hydroxyurea (HU) alone has the potential to prevent one out of every three deaths due to sickle cell disease (SCD) and almost all forms of disabilities caused by SCD. However, in Tanzania, only one out of every six registered SCD patients in the SPARCO-Tanzania Sickle Cell Cohort use HU. We conducted studies to understand factors influencing utilization of HU in Tanzania and discovered that among the reason for low utilization of HU include HU is classified as anticancer medication, only hematologists are supposed to prescribe HU, limited HU prescription to only National and Specialized hospitals, a special permit is required to access HU using National Health Insurance Fund (NHIF) scheme and limited importation and absence of local manufacturing of HU limit availability of this important drug in Tanzania. Therefore, with this brief, the government should allow prescription of HU to the district hospitals level, should allow all clinicians with a minimum of a Bachelor of Medicine to prescribe HU, and accessibility of HU through NHIF should be friendly.

Impact of hydroxyurea on hospital stay &amp; analgesic utilization in sickle cell anaemia with vaso-occlusive crises

Hydroxyurea (HU) has been useful in preventing sickle cell vaso-occlusive crises (VOC). A few studies also suggest utility of HU, during acute VOC. Sickle cell anaemia (SCA) is of high prevalence in western districts of Odisha State, India, and VOC is a common presentation, despite being mostly of Arab-Indian haplotype. This study was undertaken to evaluate the impact of HU on hospital stay and analgesic utilization in acute painful VOC of SCA. Homozygous sickle cell disease (HbSS) patients were categorized as cases who were receiving low-dose HU (10 mg/kg/day) and patients who were not on HU were considered as control. Days of hospital stay, analgesic utilization and visual analogue scale (VAS) score in patients were compared with that of control. Analgesics used to control pain were tramadol hydrochloride, ketorolac and diclofenac. A total of 359 homozygous sickle cell disease (SCD) patients with VOC were studied (187 patients and 172 controls). The patient group had lesser mean days of hospital stay (1.4 days less than controls, P<0.001) and required lesser days of analgesic utilization than controls (1.18 days less than controls, P<0.001). Significant differences were observed between patients and controls concerning VAS score and amount of tramadol hydrochloride, ketorolac and diclofenac utilization (P<0.05). In this study, HU was found to have beneficial effects in acute VOC of homozygous SCD, which includes shortening the duration of hospital stay and reducing the net amount of analgesic utilization during hospitalization.

Effects of the COVID-19 Pandemic on Caregivers of Young Children with Sickle Cell Disease Enrolled in the Engage-HU Trial

Effects of the COVID-19 Pandemic on Caregivers of Young Children with Sickle Cell Disease Enrolled in the Engage-HU Trial