Provider prescription of hydroxyurea in youth and adults with sickle cell disease: A review of prescription barriers and facilitators.

Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence-based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow-up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates.

Health literacy correlates with abbreviated full-scale IQ in adolescent and young adults with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a chronic condition with progressive neurocognitive deficits. Health literacy (HL) is essential during adolescence and young adulthood, as the transition to adult care requires healthcare decisions. HL is known to be low in SCD; however, relation between general cognitive ability and HL has not been investigated. METHODS: This cross-sectional study included adolescent and yound adults (AYAs) with SCD from two institutions. Logistic regression measured the association between HL, measured by the Newest Vital Sign tool, and general cognitive ability, measured with abbreviated full-scale intelligence quotient (FSIQ) on the Wechsler Abbreviated Scale of Intelligence. RESULTS: Our cohort contained 93 participants at two sites: 47 (51%) at Memphis, TN and 46 (49%) at St. Louis, MO, ranging from ages 15-45 years (mean = 21 years) and with a majority (70%) possessing a high school education or greater. Only 40/93 participants (43%) had adequate HL. Lower abbreviated FSIQ (p < .0001) and younger age at assessment (p = .0003) were associated with inadequate HL. For every standard score point increase in abbreviated FSIQ, the odds of having adequate HL compared to limited or possibly limited HL increase by 1.142 (95% confidence interval [CI]: 1.019-1.322) and 1.116 (95% CI: 1.045-1.209), respectively, after adjusting for age, institution, income, and educational attainment. CONCLUSIONS: Understanding and addressing HL is imperative in improving self-management and health outcomes. Among AYA with SCD, low HL was prevalent and influenced by abbreviated FSIQ. Routine screening for neurocognitive deficits and HL should be performed to guide development of interventions to adapt to the HL of AYA with SCD.

"The project did not come to us with a solution": Perspectives of research teams on implementing a study about electronic health record-embedded individualized pain plans for emergency department treatment of vaso-occlusive episodes in adults with sickle cell disease.

BACKGROUND: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises. METHODS: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared their perspectives about the implementation of ALIGN in their sites. Data were analyzed in three phases using open coding steps adapted from grounded theory and qualitative content analysis. RESULTS: A total of seven overarching themes were identified: (1) the E-IPP structure (location and upkeep) and collaboration with the informatics team, (2) the role of ED champion, (3) the role of research coordinators, (4) research team communication, and communication between research team and clinical team, (5) challenges with the study protocol, (6) provider feedback: addressing over-utilizers, patient mistrust, and the positive feedback about the intervention, and (7) COVID-19 and its effects on study implementation. CONCLUSIONS: Findings from this study contribute to learning how to implement E-IPPs for adult patients with SCD in ED. The study findings highlight the importance of early engagement with different team members, a champion from the emergency department, study coordinators with different skills and enhancement of communication and trust among team members. Further recommendations are outlined for hospitals aiming to implement E-IPP for patients with SCD in ED.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03380351; https://clinicaltrials.gov/study/NCT03380351. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319.

A multilevel mHealth intervention boosts adherence to hydroxyurea in individuals with sickle cell disease.

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSß0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

Comment on Alharbi et al. Adoption of Health Mobile Apps during the COVID-19 Lockdown: A Health Belief Model Approach. Int. J. Environ. Res. Public Health 2022, 19, 4179.

Alharbi and colleagues' article, "Adoption of health mobile apps during the COVID-19 lockdown: a Health Belief Model approach", was interesting, well-written, and informative [...].

Impact of the COVID-19 Pandemic on the Implementation of Mobile Health to Improve the Uptake of Hydroxyurea in Patients With Sickle Cell Disease: Mixed Methods Study.

BACKGROUND: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. METHODS: The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients' daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. RESULTS: The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: -8.2%; P=.14; 24 weeks: -10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B's closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. CONCLUSIONS: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may "insulate" the implementation of interventions to increase medication adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319.

Effective Recruitment Strategies for a Sickle Cell Patient Registry Across Sites from the Sickle Cell Disease Implementation Consortium (SCDIC).

Sickle cell disease (SCD) is a genetic disorder predominantly affecting people of African descent and is associated with significant morbidity and mortality. To improve SCD outcomes, the National Heart Lung and Blood Institute funded eight centers to participate in the SCD Implementation Consortium. Sites were required to each recruit 300 individuals with SCD, over 20 months. We aim to describe recruitment strategies and challenges encountered. Participants aged 15-45 years with confirmed diagnosis of SCD were eligible. Descriptive statistics were used to analyze the effectiveness of each recruitment strategy. A total of 2432 participants were recruited. Majority (95.3%) were African American. Successful strategies were recruitment from clinics (68.1%) and affiliated sites (15.6%). Recruitment at community events, emergency departments and pain centers had the lowest yield. Challenges included saturation of strategies and time constraints. Effective recruitment of participants in multi-site studies requires multiple strategies to achieve adequate sample sizes.

Intentional and unintentional nonadherence to hydroxyurea among people with sickle cell disease: a qualitative study.

Hydroxyurea is an efficacious treatment for sickle cell disease (SCD), but adoption is low among individuals with SCD. The objective of this study was to examine barriers to patients' adherence to hydroxyurea use regimens by using the intentional and unintentional medication nonadherence framework. We interviewed individuals with SCD age 15 to 49.9 years who were participants in the Sickle Cell Disease Implementation Consortium (SCDIC) Needs Assessment. The intentional and unintentional medication nonadherence framework explains barriers to using hydroxyurea and adds granularity to the understanding of medication adherence barriers unique to the SCD population. In total, 90 semi-structured interviews were completed across 5 of the 8 SCDIC sites. Among interviewed participants, 57.8% (n = 52) were currently taking hydroxyurea, 28.9% (n = 26) were former hydroxyurea users at the time of the interview, and 13.3% (n = 12) had never used hydroxyurea but were familiar with the medication. Using a constructivist grounded theory approach, we discovered important themes that contributed to nonadherence to hydroxyurea, which were categorized under unintentional (eg, Forgetfulness, External Influencers) and intentional (Negative Perceptions of Hydroxyurea, Aversion to Taking Any Medications) nonadherence types. Participants more frequently endorsed adherence barriers that fell into the unintentional nonadherence type (70%) vs intentional nonadherence type (30%). Results from this study will help SCD health care providers understand patient choices and decisions as being either unintentional or intentional, guide tailored clinical discussions regarding hydroxyurea therapy, and develop specific, more nuanced interventions to address nonadherence factors.

Development of the InCharge Health Mobile App to Improve Adherence to Hydroxyurea in Patients With Sickle Cell Disease: User-Centered Design Approach.

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder causing acute complications and chronic progressive end organ damage. SCD is associated with significant morbidity, early mortality, impaired health-related quality of life, and increased acute health care utilization. Hydroxyurea is a US Food and Drug Administration-approved medication that reduces disease complications, acute health care utilization, and costs. However, adherence to hydroxyurea is suboptimal. Mobile health (mHealth) interventions have the potential to improve hydroxyurea adherence, but few examples exist that are specific to the SCD population. OBJECTIVE: This study aimed to design a mHealth intervention for individuals with SCD to improve adherence to hydroxyurea, using a user-centered design that was informed by specific barriers to hydroxyurea adherence and utilization in this population. METHODS: This study consisted of 4 phases. In phase 1, individuals with SCD and health care providers participated in an optimization digital workshop. In phase 2, patients completed surveys pertaining to their interest in mHealth use, barriers and facilitators to hydroxyurea use, and health literacy. Phases 3 and 4 involved semistructured interviews and focus groups, respectively, and used the Health Belief Model (HBM) as the framework to investigate drivers of poor hydroxyurea adherence and to inform the development of an app prototype. In addition, in phase 4, we have incorporated the patients' feedback on the preliminary app prototype and its features. RESULTS: Barriers to hydroxyurea adherence were consistent with the literature and included forgetfulness and several specific thoughts and emotions associated with hydroxyurea use (eg, fear of side effects, depression, stigma, and hopelessness). In addition, more than half of the participants reported potentially low health literacy. Preferred patient app features included 7 key components, namely (1) medication reminders and tracker, (2) disease education, (3) communication, (4) personalization, (5) motivation, (6) support during pain episodes, and (7) social support. Utilizing a user-centered design approach, data obtained from patients and providers were translated into features within the app, mapping to components of the HBM and the specific drivers of hydroxyurea adherence and matching the literacy level of the population, resulting in the development of a novel mobile app called InCharge Health. CONCLUSIONS: The InCharge Health app is an mHealth intervention developed with substantial input from users and by mapping the HBM as the framework that guided the choice for its components. InCharge Health is a customized product for the SCD population aimed at optimizing medication adherence, with the end goal of improving quality of life and health outcomes among patients with SCD. The efficacy and implementation of the InCharge Health app as an mHealth intervention to promote hydroxyurea adherence will be tested in a future stepped-wedge multicenter trial for adolescents and adults with SCD.