Developing an Implementation Blueprint for the NIH HEAL Initiative GRACE Trial: Perspectives on Acupuncture and Guided Relaxation for Chronic Sickle Cell Disease Pain.

Objective: This study aimed to explore perspectives of people living with sickle cell disease (SCD) and SCD clinic providers and staff about the use of acupuncture and guided relaxation for treating chronic SCD pain. Data obtained were to inform an implementation blueprint for an effectiveness implementation clinical trial (GRACE Trial) testing whether acupuncture or guided relaxation reduces chronic pain when compared with usual care. Design: Qualitative research design. Methods: We conducted 33 semistructured interviews with people with SCD and SCD clinic providers and staff. Interviews were transcribed and coded. A deductive content analysis process was used to identify themes. Results: Four themes were identified: Receptivity to Acupuncture and Guided Relaxation, Limited Awareness, Complementary and Integrative Health (CIH) Therapy Preference, and Access Barriers. Both patients and clinic providers and staff were open to the use of acupuncture and guided relaxation for chronic pain treatment. After learning about these CIH therapies, some patients expressed a preference for one therapy over the other. They also discussed their ability to successfully engage with each therapy. There is a need to dispel misconceptions about the therapies by increasing understanding of how each therapy is implemented and functions to reduce pain. We identified several potential barriers that might affect the success of the trial and future health system integration, including time, transportation, and technology. Conclusion: This study is one of the first to present perspectives of both patients with SCD and clinic providers and staff on the use of acupuncture and guided relaxation for chronic SCD pain. Stakeholders' early input and perspectives highlighted that they welcome nonpharmacological CIH therapies. Implementation of a clinical trial and future health system integration will require the addressing misinformation and identifying strategies to overcome access barriers. Clinical trial registration number: NCT04906447.

Hybrid effectiveness-implementation trial of guided relaxation and acupuncture for chronic sickle cell disease pain (GRACE): A protocol.

Background: People with sickle cell disease frequently use complementary and integrative therapies to cope with their pain, yet few studies have evaluated their effectiveness. The 3-arm, 3-site pragmatic Hybrid Effectiveness-implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain (GRACE) has 3 priorities: (1) evaluate guided relaxation and acupuncture to improve pain control; (2) determine the most appropriate and effective treatment sequence for any given patient based on their unique characteristics; and (3) describe the processes and structures required to implement guided relaxation and acupuncture within health care systems. Methods: Participants (N = 366) are being recruited and randomized 1:1:1 to one of 2 intervention groups or usual care. The acupuncture intervention group receives 10 sessions over approximately 5 weeks. The guided relaxation intervention group receives access to video sessions ranging from 2 to 20 min each viewed daily over 5 weeks. The usual care group receives the standard of clinical care for sickle cell disease. Participants are re-randomized at 6 weeks depending on their pain impact score. Assessments occur at 6 weeks, 12 weeks, and 24 weeks. The primary outcome is the change in pain impact score and secondary measures include opioid use, anxiety, depression, sleep, pain catastrophizing, substance use, global impression of change, constipation, and hospitalizations. The GRACE study uses the Consolidated Framework for Implementation Research to plan, execute, and evaluate the associated implementation processes. Conclusion: The results from GRACE will represent a critical step toward improving management of pain affecting patients with sickle cell disease.ClinicalTrials.gov Identifier: NCT04906447.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Adherence to Iron Chelation Therapy with Deferasirox Formulations among Patients with Sickle Cell Disease and ß-thalassemia.

BACKGROUND: Individuals with hemoglobinopathies experience complications that often require management with multiple transfusions. These chronic transfusions can lead to iron overload, which places them at increased risk of organ damage, malignancy, and even death. Deferasirox is the most common iron chelator used to treat iron overload due to its safety, efficacy, and oral administration. The first formulation of deferasirox, a dispersible tablet for oral suspension (DT) called Exjade®, was associated with adherence challenges due to complaints from poor taste and side effects such as abdominal discomfort. A new film-coated tablet formulation (FCT) called Jadenu® was subsequently developed to overcome these challenges. OBJECTIVE: The objective of this study was to compare adherence rates between formulations of deferasirox (DT versus FCT) and describe associations between adherence to chelation therapy and changes in hematological parameters among patients with SCD and ß-thalassemia. METHODS: In this retrospective study of 20 children and adults with sickle cell disease (SCD) and ß-thalassemia with iron overload, we compared adherence rates for deferasirox DT versus deferasirox FCT. We reviewed data from the electronic medical record and pharmacy expense reports between 2014 and 2018. We calculated the mean medication possession ratio (MPR) and analyzed the mean paired difference in MPR and ferritin levels using paired sample t-test. RESULTS: The overall mean MPR was 0.15 (0.25) for deferasirox DT and 0.44 (0.32) for deferasirox FCT. The mean paired difference in MPR when transitioning from deferasirox DT to deferasirox FCT was +0.29, p-value < 0.01 (95% CI: 0.19, 0.39). The mean paired difference in ferritin while on deferasirox DT compared to ferritin 6 months after transitioning to deferasirox FCT was -306 ng/mL p-value = 0.14 (95% CI: 719, 113). CONCLUSION: There was significant improvement in adherence to iron chelation therapy when patients transitioned from deferasirox DT to deferasirox FCT.

Advances in iron chelation therapy: transitioning to a new oral formulation.

Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consideration and may be affected by side effects. A new formulation of deferasirox, a film-coated tablet (FCT), has the potential to improve adherence by offering greater flexibility in administration compared with the original formulation of deferasirox, a dispersible tablet (DT) for oral suspension. This review provides an overview of the currently available iron chelator formulations, with a focus on a comparison between deferasirox DT for oral suspension and deferasirox FCT. The new formulation may be associated with fewer side effects and has increased bioavailability. In addition, alternative strategies for iron chelation, such as combining two different iron chelators, will be discussed.

Utilizing a Novel Mobile Health "Selfie" Application to Improve Compliance to Iron Chelation in Pediatric Patients Receiving Chronic Transfusions.

Iron chelation therapy can prevent iron overload for pediatric patients with sickle cell disease and ß-thalassemia major; however, adherence is suboptimal. Therefore, we developed an intensive training program (ITP), to improve medication management and disease knowledge. The objectives were to determine feasibility of the ITP and its preliminary impact on adherence, disease knowledge, and health outcomes. Pediatric patients were recruited to participate in the ITP over a 90-day period and were followed for 6 months. The ITP consisted of 3 components: (1) provider-led education modules; (2) patient recording daily videos of at-home medication administration; and (3) provider feedback through video messages through the ITP app. Eleven patients participated (mean=12.4 y). Initially, patients endorsed high satisfaction and ease of use and tracked their medication usage 81% (24 out of 30) of days. At 90 days, adherence rates remained consistent (80%) and disease knowledge retention was high (96%). At 6 months, participants exhibited a clinically relevant decrease in serum ferritin, which trended toward statistical significance (P=0.068). Medication possession ratio did not significantly increase (0.65 to 0.72; not significant). The mobile ITP was feasibly implemented in a clinical setting; in addition, high levels of compliance, disease knowledge retention, and acceptance encourage larger studies evaluating mobile health technology to improve child health parameters.