Bidirectional processes linking social determinants of health and pediatric sickle cell anemia management: A qualitative study.

BACKGROUND: Children with sickle cell anemia (SCA) have substantial medical needs and more unmet basic needs than children with other medical conditions. Despite a recent focus on social determinants of health (SDoH), there remains an incomplete understanding of the processes linking SDoH and disease management, particularly for youth with SCA. This study elucidated these processes and identified ways to mitigate deleterious effects of adverse SDoH on SCA management. METHODS: Parents/primary caregivers (N = 27) of children with SCA (≤12 years old) participated in semi-structured interviews regarding SCA management and SDoH and completed quantitative measures of basic needs. Qualitative data were systematically coded and analyzed using applied thematic analysis. Quantitative data were presented descriptively. RESULTS: Three qualitative themes were identified. First, SCA management is bidirectionally linked with the social environment, whereby challenges of SCA management can hinder basic needs from being met, and unmet basic needs and financial hardship hinder SCA management. Second, due to limited resources, parents/caregivers are faced with difficult choices between prioritizing basic needs versus SCA management. Third, addressing material, emotional, and informational needs may improve SCA management. Quantitatively, 73% of families endorsed ≥1 basic need, including food insecurity (42%), housing instability (62%), and/or energy insecurity 19% (vs. 20%). CONCLUSION: Despite documented associations, there remains a poor understanding of the processes linking SDoH and health. Findings underscore how day-to-day conditions undermine the management of SCA treatments, symptoms, and complications, limiting treatment effectiveness. Understanding these processes may inform family-centered, health equity interventions and policies to improve living conditions, disease management, and health outcomes.

Sickle Cell Disease: A Review.

Importance: Sickle cell disease (SCD) is an inherited disorder of hemoglobin, characterized by formation of long chains of hemoglobin when deoxygenated within capillary beds, resulting in sickle-shaped red blood cells, progressive multiorgan damage, and increased mortality. An estimated 300 000 infants are born annually worldwide with SCD. Most individuals with SCD live in sub-Saharan Africa, India, the Mediterranean, and Middle East; approximately 100 000 individuals with SCD live in the US. Observations: SCD is diagnosed through newborn screening programs, where available, or when patients present with unexplained severe atraumatic pain or normocytic anemia. In SCD, sickling and hemolysis of red blood cells result in vaso-occlusion with associated ischemia. SCD is characterized by repeated episodes of severe acute pain and acute chest syndrome, and by other complications including stroke, chronic pain, nephropathy, retinopathy, avascular necrosis, priapism, and leg ulcers. In the US, nearly all children with SCD survive to adulthood, but average life expectancy remains 20 years less than the general population, with higher mortality as individuals transition from pediatric to adult-focused health care systems. Until 2017, hydroxyurea, which increases fetal hemoglobin and reduces red blood cell sickling, was the only disease-modifying therapy available for SCD and remains first-line therapy for most individuals with SCD. Three additional therapies, L-glutamine, crizanlizumab, and voxelotor, have been approved as adjunctive or second-line agents. In clinical trials, L-glutamine reduced hospitalization rates by 33% and mean length of stay from 11 to 7 days compared with placebo. Crizanlizumab reduced pain crises from 2.98 to 1.63 per year compared with placebo. Voxelotor increased hemoglobin by at least 1 g/dL, significantly more than placebo (51% vs 7%). Hematopoietic stem cell transplant is the only curative therapy, but it is limited by donor availability, with best results seen in children with a matched sibling donor. While SCD is characterized by acute and chronic pain, patients are not more likely to develop addiction to pain medications than the general population. Conclusions and Relevance: In the US, approximately 100 000 people have SCD, which is characterized by hemolytic anemia, acute and chronic pain, acute chest syndrome; increased incidence of stroke, nephropathy, and retinopathy; and a life span that is 20 years shorter than the general population. While hydroxyurea is first-line therapy for SCD, L-glutamine, crizanlizumab, and voxelotor have been approved in the US since 2017 as adjunctive or second-line treatments, and hematopoietic stem cell transplant with a matched sibling donor is now standard care for severe disease.

Addressing unmet basic needs for children with sickle cell disease in the United States: clinic and staff perspectives.

BACKGROUND: The purpose of this study was to assess pediatric hematology clinic staff's perspectives regarding barriers and facilitators in addressing unmet basic needs for children with sickle cell disease (SCD). METHODOLOGY: Six focus groups were held at four urban pediatric hematology clinics in the Northeastern region of the United States from November to December 2019. Discussion questions were developed to align with the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) implementation science framework, focusing on the domains of context and recipient and how clinics address adverse social determinants of health (SDoH) in their patient populations. A summative content analytical approach was taken to identify major themes in the data. RESULTS: We discerned the following themes: (1) families of children with SCD experience numerous unmet basic needs; (2) clinic staff believed they had a role to play in addressing these unmet basic needs; (3) staff felt their ability to address families' unmet basic needs depended upon caregivers' capacity to act on staff's recommendations; and (4) clinic staff's ability to address these needs was limited by organizational and systemic factors beyond their control. CONCLUSIONS: These findings have important implications for how best to address adverse SDoH for this vulnerable pediatric population so that urban-based pediatric hematology clinics can more equitably support families.

Developing a Problem-solving Intervention to Improve Self-Management and Transition Readiness in Adolescents with Sickle Cell Disease.

PURPOSE: Adolescents and young adults (AYA) with sickle cell disease (SCD) are at risk for serious complications including increased morbidity and early mortality during their transition from pediatric to adult care. Self-management support may help improve transition outcomes in this vulnerable population. Interventions based on teaching problem solving skills have been shown to improve adherence to therapy for AYA with other chronic disease and is a promising intervention in SCD. We sought patient and parent perspectives on improving self-management and input on the development of a problem-solving education (PSE) intervention. DESIGN AND METHODS: We held focus groups with AYA with SCD and caregivers to discuss barriers and facilitators of self-management, acceptability of PSE and intervention content and delivery. RESULTS: Five focus groups were held with AYA (n = 17) and caregivers (n = 15). Groups participated jointly to discuss self-management and then separately to discuss PSE. Data were analyzed using grounded theory and double-coded until thematic saturation was achieved. CONCLUSIONS: Both groups endorsed PSE as an acceptable intervention. Barriers to self-management included wanting to fit in with peers (AYA) and trouble letting go (parents); facilitators included having a regular routine (AYA) and sharing responsibility (parents). Participants suggested meeting in small groups for PSE sessions rather than individually and adding group sessions for parents. PRACTICAL IMPLICATIONS: Understanding AYA and caregivers' perceptions of barriers and facilitators of transition in SCD can help us better prepare AYA for transition. The specifics both groups identified as helpful will guide intervention development.

Improvement in influenza vaccination rates in a pediatric sickle cell disease clinic.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk of complications from influenza. However, despite widespread recommendations that these patients receive an annual influenza immunization, reported vaccination rates remain very low at under 50%. PROCEDURE: Our aim was to increase the influenza vaccination rate among our pediatric patients with SCD aged 6 months to 21 years over two influenza seasons, 2012-2013 and 2013-2014, to 80%, consistent with the Health People 2020 goal. We used multiple quality improvement methods, based on the literature and our previous experience in other aspects of SCD care, including parent and provider education, enhancement of our EHR, use of a SCD patient registry and reminder and recall done by a patient navigator. RESULTS: We vaccinated 80% of our pediatric patients with SCD for influenza during the 2012-2013 season and 90% of patients in 2013-2014. Our early season vaccination rates were nearly double that of those for the general population. CONCLUSIONS: Use of quality improvement methods can increase rates of influenza vaccination for this high-risk population, suggesting that less health care utilization and lower cost might result.

Effects of Experienced Discrimination in Pediatric Sickle Cell Disease: Caregiver and Provider Perspectives.

For Black children with sickle cell disease (SCD) and their families, high disease stigmatization and pervasive racism increase susceptibility to discrimination in healthcare settings. Childhood experiences of discrimination can result in medical nonadherence, mistrust of healthcare providers, and poorer health outcomes across the lifespan. Caregivers and medical providers are essential to childhood SCD management and are therefore well-positioned to provide insight into discrimination in the context of pediatric SCD. This mixed-methods study sought caregivers' and providers' perspectives on processes underlying discrimination and potential solutions to mitigate the negative effects of perceived discrimination among children with SCD. Caregivers (N = 27) of children with SCD (≤ 12 years old) and providers from their hematology clinics (N = 11) participated in individual semi-structured interviews exploring experiences of discrimination and daily SCD management and completed a quantitative measure of discrimination. Qualitative data were collected until themes reached saturation and subsequently transcribed verbatim, coded, and analyzed using applied thematic analysis. Quantitative and qualitative data converged to suggest the pervasiveness of discrimination in healthcare settings. Three qualitative themes emerged: (1) healthcare system factors underlie discrimination, (2) families' challenging interactions with providers lead to perceptions of discrimination, and (3) experiences of discrimination impact caregiver-provider interactions. Both caregivers and providers highlighted building trusting patient-provider relationships and encouraging patients' self-advocacy as means to reduce experiences and impacts of discrimination. These findings offer potential approaches to tangibly mitigate occurrences of discrimination in pediatric healthcare settings by trust building, accountability keeping, and fostering rapport to improve quality of care and pediatric SCD health outcomes.

A comparison of the effect of patient-specific versus weight-based protocols to treat vaso-occlusive episodes in the emergency department.

BACKGROUND: Vaso-occlusive crises (VOCs) cause debilitating pain and are a common cause of emergency department (ED) visits, for people with sickle cell disease (SCD). Strategies for achieving optimal pain control vary widely despite evidence-based guidelines. We tested existing guidelines and hypothesized that a patient-specific pain protocol (PSP) written by their SCD provider may be more effective than weight-based (WB) dosing of parenteral opiate medication, in relieving pain. METHODS: This study was a prospective, randomized controlled trial comparing a PSP versus WB protocol for patients presenting with VOCs to six EDs. Patients were randomized to a PSP or WB protocol prior to an ED visit. The SCD provider wrote their protocol and placed it in the electronic health record for future ED visits with VOC exclusion criteria that included preexisting PSP excluding parenteral opioid analgesia or outpatient use of buprenorphine or methadone or highly suspected for COVID-19. Pain intensity scores, side effects, and safety were obtained every 30 min for up to 6 h post-ED bed placement. The primary outcome was change in pain intensity score from placement in an ED space to disposition or 6 h. RESULTS: A total of 328 subjects were randomized; 104 participants enrolled (ED visit, target n = 230) with complete data for 96 visits. The study was unable to reach the target sample size and stopped early due to the impact of COVID-19. We found no significant differences between groups in the primary outcome; patients randomized to a PSP had a shorter ED length of stay (p = 0.008), and the prevalence of side effects was low in both groups. Subjects in both groups experienced both a clinically meaningful and a statistically significant decrease in pain (27 mm on a 0- to 100-mm scale). CONCLUSIONS: We found a shorter ED length of stay for patients assigned to a PSP. Patients in both groups experienced good pain relief without significant side effects.

Setting the agenda for quality improvement in pediatric sickle cell disease.

OBJECTIVE: Despite recent scientific advances, children with sickle cell disease (SCD) continue to experience high mortality and significant morbidity, in part due to variations in the care provided. We sought to identify and compare drivers for quality improvement among clinical staff and parents of children with SCD. METHODS: We interviewed clinical staff across care settings in an urban teaching hospital to elicit their perspectives on improving care for children with SCD. Concurrently, we invited parents of children with SCD to participate in focus groups to identify their needs. Findings are reported according to Consolidated Criteria for Reporting Qualitative Research guidelines. RESULTS: We conducted 29 interviews with clinical staff and 4 focus groups with parents. Both groups identified the need for effective communication of relevant patient information across disciplines as a key area for improvement. Clinical staff cited standardization of care delivery as a top priority through increased accessibility of pertinent clinical information, enhanced pain assessment and management, and improved availability of clinical decision-making tools. Parents listed the need for increased community awareness about SCD, including school and day care staff, enhanced parental education and peer support, and self-management skills for their children as opportunities to improve pediatric SCD care. CONCLUSIONS: Identifying drivers for quality improvement is a critical first step in transforming the care provided to children with SCD. Using a systematic approach that includes eliciting the perspectives of both clinicians and parents may significantly enhance the development of a patient-centered quality improvement agenda.

Translating scientific advances to improved outcomes for children with sickle cell disease: a timely opportunity.

Despite the recent advances made in the care of children with sickle cell disease (SCD), premature mortality, especially among older children and young adults, remains a hallmark of this disease. The lack of survival gains highlights the translational gap of implementing innovations found efficacious in the controlled trial setting into routine clinical practice. Health services research (HSR) examines the most effective ways to finance, organize, and deliver high quality care in an equitable manner. To date, HSR has been underutilized as a means to improve the outcomes for children with SCD. Emerging national priorities in health care delivery, new sources of funding, and evolving electronic data collection systems for patients with SCD have provided a unique opportunity to overcome the translational gap in pediatric SCD. The purpose of this article is to provide a comprehensive HSR agenda to create patient-specific evidence of clinical effectiveness for interventions used in the routine care setting, understand the barriers faced by clinicians to providing high quality care, assess and improve the interactions of patients with the health care system, and measure the quality of care delivered to increase survival for all children and young adults with SCD.

Optimizing a literature surveillance strategy to retrieve sound overall prognosis and risk assessment model papers.

OBJECTIVE: Our aim was to develop an efficient search strategy for prognostic studies and clinical prediction guides (CPGs), optimally balancing sensitivity and precision while independent of MeSH terms, as relying on them may miss the most current literature. MATERIALS AND METHODS: We combined 2 Hedges-based search strategies, modified to remove MeSH terms for overall prognostic studies and CPGs, and ran the search on 269 journals. We read abstracts from a random subset of retrieved references until ≥ 20 per journal were reviewed and classified them as positive when fulfilling standardized quality criteria, thereby assembling a standard dataset used to calibrate the search strategy. We determined performance characteristics of our new search strategy against the Hedges standard and performance characteristics of published search strategies against the standard dataset. RESULTS: Our search strategy retrieved 16 089 references from 269 journals during our study period. One hundred fifty-four journals yielded ≥ 20 references and ≥ 1 prognostic study or CPG. Against the Hedges standard, the new search strategy had sensitivity/specificity/precision/accuracy of 84%/80%/2%/80%, respectively. Existing published strategies tested against our standard dataset had sensitivities of 36%-94% and precision of 5%-10%. DISCUSSION: We developed a new search strategy to identify overall prognosis studies and CPGs independent of MeSH terms. These studies are important for medical decision-making, as they identify specific populations and individuals who may benefit from interventions. CONCLUSION: Our results may benefit literature surveillance and clinical guideline efforts, as our search strategy performs as well as published search strategies while capturing literature at the time of publication.

A National Measurement Framework to Assess and Improve Sickle Cell Care in 4 US Regions.

OBJECTIVES: Coordinated measurement strategies are needed to inform collaborative approaches to improve access to and quality of care for persons with sickle cell disease (SCD). The objective of our study was to develop a multilevel measurement strategy to assess improvements in access to and quality of care for persons with SCD in 4 US regions. METHODS: From 2014 through 2017, regional grantees in the Sickle Cell Disease Treatment Demonstration Program collected administrative and patient-level electronic health record (EHR) data to assess quality improvement initiatives. Four grantees-covering 29 US states and territories and an SCD population of 56 720-used a collective impact model to organize their work. The grantees collected administrative data from state Medicaid and Medicaid managed care organizations (MCOs) at multiple points during 2014-2017 to assess improvements at the population level, and local patient-level data were abstracted from site-level EHRs at regular intervals to track improvements over time. RESULTS: Administrative data were an important source of understanding population-level improvements but were delayed, whereas patient-level data were more sensitive to small-scale quality improvements. CONCLUSIONS: We established a shared measurement approach in partnership with Medicaid and Medicaid MCO stakeholders that can be leveraged to effectively support quality improvement initiatives for persons with SCD in the United States.

Health care utilization and expenditures for privately and publicly insured children with sickle cell disease in the United States.

BACKGROUND: There are no current national estimates on health care utilization and expenditures for US children with sickle cell disease (SCD). PROCEDURE: We used the MarketScan Medicaid Database and the MarketScan Commercial Claims and Encounters Database for 2005 to estimate health services use and expenditures. The final samples consisted of 2,428 Medicaid-enrolled and 621 privately insured children with SCD. RESULTS: The percentage of children with SCD enrolled in Medicaid with an inpatient admission was higher compared to those privately insured (43% vs. 38%), yet mean expenditures per admission were 35% lower ($6,469 vs. $10,013). The mean number of emergency department (ED) visits was 49% higher for Medicaid-enrolled children compared to those with private insurance (1.36 vs. 0.91), but mean expenditures per ED visit were 28% lower. The mean number of non-ED outpatient visits was similar (12.6 vs. 11.5) but mean expenditures were 40% lower for the Medicaid-enrolled children ($3,557 vs. $5,908). The mean expenditures on drug claims were higher among those with Medicaid than private insurance ($1,049 vs. $531). Mean total expenditures for children with SCD enrolled in Medicaid were 25% lower than for privately insured children ($11,075 vs. $14,722). The samples were comparable with respect to SCD-related inpatient discharge diagnoses and use of outpatient blood transfusions. CONCLUSIONS: Children with SCD enrolled in Medicaid had lower expenditures than privately insured children, despite higher utilization of medical care, which indicates lower average reimbursements. Research is needed to assess the quality of care delivered to Medicaid-enrolled children with SCD and its relation to health outcomes.

Communication of positive newborn screening results for sickle cell disease and sickle cell trait: variation across states.

In the US, all states and the District of Columbia have universal newborn screening (NBS) programs for sickle cell disease (SCD), which also identify sickle cell trait (trait). In this project, we surveyed follow-up coordinators, including one in the District of Columbia and two in Georgia, about protocols for stakeholder notification for SCD and trait. The primary outcomes were total number and type of stakeholder informed of a positive screen. We received 52 completed surveys (100% response). Primary care providers (PCPs) (100%), hematologists (81%), hospitals (73%), and families (40%) were the most commonly notified stakeholders of positive SCD screens, while PCPs (88%), hospitals (63%), and families (37%) were most commonly notified for trait. On average, 3.4 stakeholders were notified for a positive screening for SCD, compared to 2.4 stakeholders for sickle cell trait (P < 0.001). In multivariate analyses for SCD, we found a 2.9% increase in stakeholders notified for each additional year of universal screening mandated in a state (95% CI: 1.4-4.4%). For trait, we found an 8.5% increase in stakeholders notified for each additional follow-up staff (95% CI: 1.3-15.7%), and a 1.3% increase for each additional percent of black births in the state (95% CI: 0.1-2.5%). Wide variation exists in stakeholder notification by NBS programs of positive screenings for SCD and trait. This variation may alter the effectiveness of NBS programs by location of birth.

Improving the Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department.

OBJECTIVES: Vaso-occlusive episodes (VOEs) account for the majority of emergency department (ED) visits for children with sickle cell disease (SCD). We hypothesized that addressing key barriers to VOE care would improve receipt of analgesics and outcomes. METHODS: A quality improvement (QI) initiative was conducted from September 2010 to April 2014 to streamline VOE care in an urban pediatric ED. Four interventions were used: a standardized time-specific VOE protocol; intranasal fentanyl as the first parenteral pain medication; an SCD pain medication calculator; and provider and patient/family education. Data were collected for 3 outcome measures (mean time from triage to first parenteral opioid and admission/discharge decision, and proportion discharged from the ED); 1 process measure (mean time from triage to initiation of patient-controlled analgesia); and 4 balancing measures (mean time from triage to second intravenous opioid dose, 24-hour ED readmission, respiratory depression, and length of stay). RESULTS: There were 289 ED visits in the study period. Improvements were seen in mean time to: first dose of parenteral opioid (56 to 23 minutes); second opiate intravenous dose (106 to 83 minutes); admission and discharge decisions (163 to 109 minutes and 271 to 178 minutes, respectively); and initiation of patient-controlled analgesia (216 to 141 minutes). The proportion discharged from the ED increased from 32% to 48% (χ(2) = 6.5402, P = .01). No increase in 24-hour readmission, respiratory depression, or inpatient length of stay was observed. CONCLUSIONS: Using VOE-specific interventions, we significantly improved VOE care for children. Studies are needed to determine if these results can be replicated.

Medication adherence among pediatric patients with sickle cell disease: a systematic review.

OBJECTIVES: Describe rates of adherence for sickle cell disease (SCD) medications, identify patient and medication characteristics associated with nonadherence, and determine the effect of nonadherence and moderate adherence (defined as taking 60%-80% of doses) on clinical outcomes. METHODS: In February 2012 we systematically searched 6 databases for peer-reviewed articles published after 1940. We identified articles evaluating medication adherence among patients <25 years old with SCD. Two authors reviewed each article to determine whether it should be included. Two authors extracted data, including medication studied, adherence measures used, rates of adherence, and barriers to adherence. RESULTS: Of 24 articles in the final review, 23 focused on 1 medication type: antibiotic prophylaxis (13 articles), iron chelation (5 articles), or hydroxyurea (5 articles). Adherence rates ranged from 16% to 89%; most reported moderate adherence. Medication factors contributed to adherence. For example, prophylactic antibiotic adherence was better with intramuscular than oral administration. Barriers included fear of side effects, incorrect dosing, and forgetting. Nonadherence was associated with more vaso-occlusive crises and hospitalizations. The limited data available on moderate adherence to iron chelation and hydroxyurea indicates some clinical benefit. CONCLUSIONS: Moderate adherence is typical among pediatric patients with SCD. Multicomponent interventions are needed to optimally deliver life-changing medications to these children and should include routine monitoring of adherence, support to prevent mistakes, and education to improve understanding of medication risks and benefits.