Emergency department 30-Day emergency department revisits among people with sickle cell disease: Variations in characteristics.

People with sickle cell disease (SCD) often have emergency department (ED) revisits. The characteristics of people with SCD with ED revisits were assessed in this study using Medicaid administrative claims data from California and Georgia, representing 2794 and 3641 individuals with SCD, respectively. In both states, those with 6+ primary care provider (PCP) encounters had the highest percentage of ED revisits. In California, those with 6+ hematology encounters had the lowest percentage of individuals with an ED revisit; in Georgia, those with 1-2 hematology encounters. Increasing access to hematologic care may reduce ED revisits among people with SCD.

Characterizing medical decision-making in sickle cell disease during childhood: Qualitative perspectives of caregivers.

INTRODUCTION: Sickle cell disease (SCD) is the most common genetic disorder among children. As the most common type of SCD, sickle cell anemia (SCA) is associated with severe complications across the lifespan. As parents/caregivers hold primary disease management responsibility during childhood, their involvement in disease management activities, including medical decision-making, is critical to successful and timely management of pediatric SCD. However, the processes through which caregivers make SCD-related decisions remain unknown. The current paper examined caregivers' decision-making processes and priorities when managing their child's SCD. METHODS: Parents and primary caregivers (N = 27) of children with SCA (ages 0-12) completed individual semi-structured qualitative interviews exploring links between caregivers' decision-making and both daily and ongoing SCA management practices. Data were transcribed verbatim, cleaned, systematically coded, and analyzed using applied thematic analysis. RESULTS: Participating caregivers were primarily Black or African American (88.9%), mothers (81.5%), publicly insured (55.6%), and single (51.9%). Caregivers described medical decision-making across acute symptom response, preventive disease management, and treatment initiation and/or discontinuation. Across these contexts of disease management, caregivers overarchingly prioritized protecting and improving their child's quality of life. Caregivers' medical decision-making processes were influenced by their SCA management experience, acquisition of SCA knowledge, and trust in medical providers. The extent to which these influences impacted caregivers' decision-making varied based on disease severity, disease management experience, and time since diagnosis. DISCUSSION: Findings highlight how processes underlying caregivers' decision-making are directly influenced and informed by caregivers' lived experiences. Future work should develop provider-initiated collaborative interventions to support medical decision-making.

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.

Increased platelet reactivity as measured by plasma glycoprotein VI in gout.

Patients with gout have an increased risk of cardiovascular events. The glycoprotein VI (GPVI) receptor is found exclusively on platelets and megakaryocytes, is proteolytically cleaved upon platelet activation, and detectable in plasma as soluble GPVI (sGPVI). Therefore, elevated sGPVI is a marker of platelet activation and a risk marker for cardiovascular events. The aim of this study was to assess platelet activation, as measured by plasma sGPVI level in gout. Blood samples were taken from patients with gout or osteoarthritis, and from healthy volunteers. Demographic and clinical data were collected for all participants. Blood samples were processed as double-spun platelet-poor plasma. Plasma sGPVI levels were measured using enzyme-linked immunosorbent assay. Mann-Whitney U test was used to compare groups. In total, 91 patients were included, 27 during gout flare, 41 with intercritical gout, 23 with osteoarthritis, and 53 healthy controls. Median (interquartile range) sGPVI levels were 6.51 ng/mL (4.52, 8.41) in gout flare, 3.58 ng/mL (2.11, 5.55) in intercritical gout, 2.73 ng/mL (2.17, 3.72) in osteoarthritis, and 2.19 ng/mL (1.72, 3.31) in healthy controls. Plasma sGPVI levels in both gout groups were significantly increased compared to healthy controls (p < 0.005 for each), in gout flare compared to osteoarthritis (p < 0.005), and in gout flare compared to intercritical gout (p = 0.001). There was no significant difference in sGPVI levels in gout patients with and without tophi or in those prescribed colchicine. We conclude that patients with gout exhibit platelet hyperactivity as demonstrated by elevated sGPVI levels. Platelet activation is exacerbated in gout, especially during gout flares.

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.

Comparison of Measures of Pain Intensity During Sickle Cell Disease Vaso-Occlusive Episodes.

We aimed to determine the minimal clinically important difference (MCID) in pain severity and agreement between the visual analog scale (VAS) and the verbal numeric rating scale (NRS) in people with sickle cell disease (SCD) experiencing an acute vaso-occlusive episode in the emergency department. In the COMPARE-VOE trial (NCT03933397), participants were administered the VAS (0-100), NRS (0-100), and descriptor scale (a lot better, a little better, same, a little worse, much worse) every 30 minutes while in the emergency department. We analyzed data from 100 participants (mean age 30.2 years; 61% female). We calculated the mean differences and 95% confidence intervals (CIs) between current and preceding scores when the participant reported a little worse or a little better pain for each scale (255 VAS and 150 NRS observations) to assess the MCID for the VAS and NRS. Pearson correlation and the Bland-Altman method were used to assess the agreement among 411 paired VAS and NRS observations. Our results indicated that the MCID for the VAS was 8.77 mm (95% CI: 7.43 mm, 10.83 mm) and the NRS was 8.29 (95% CI: 6.47, 11.60). The VAS and NRS scales had a correlation of .88 (P < .001). The Bland-Altman method indicated a mean difference of -4.6 ± 1.96 and the 95% limits of agreement ranged from 20 to -29. Despite high correlation, there was considerable variability of agreement between the VAS and NRS scales, indicating that these scales are not interchangeable to assess pain during a vaso-occlusive event. PERSPECTIVE: The MCID in pain severity for individuals with a SCD vaso-occlusive episode using the VAS (8.77 mm) is lower than previously reported, and the MCID for NRS was 8.29. The agreement between the VAS and NRS was determined and the scales cannot be used interchangeably to measure SCD pain intensity.

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.

Trial design of comparing patient-specific versus weight-based protocols to treat vaso-occlusive episodes in sickle cell disease (COMPARE-VOE).

OBJECTIVES: Painful vaso-occlusive episodes (VOE) are the most common reason for emergency department (ED) visits experienced by patients with sickle cell disease (SCD). The National Heart, Lung and Blood Institute (NHLBI) evidence-based recommendations for VOE treatment are based primarily on expert opinion. In this randomized controlled trial (RCT), we will compare changes in pain scores between patients randomized to a patient-specific analgesic protocol versus those randomized to a weight-based analgesic protocol, as recommended by the NHLBI guidelines. METHODS: We report the rationale and design of a multi-site, phase III, single-blinded, RCT to be conducted in six EDs in the United States. Eligible participants will be randomized after providing consent, anticipating 50% of those randomized would have an ED visit during the enrollment period. A total of 230 participants with one VOE ED visit provides sufficient power to detect a clinically significant difference in pain score reductions of 14 between groups with 0.05 type I error. Uniquely, this trial randomizes participants in a larger population than the study population, given the impossibility of consenting and randomizing participants during emergencies. The primary endpoint is the change in pain scores in the ED from time of placement in treatment area to time of disposition (hospitalization, discharged home, or assigned to observation status) or a maximum treatment duration of 6 hours. Additional outcomes include hospitalizations and ED visits seven days post enrollment, side effects, and safety assessments. CONCLUSIONS: The COMPARE-VOE study design will provide high-level evidence to support the NHLBI VOE treatment guidelines.