Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: A multicenter pediatric emergency medicine perspective.

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study.

Parental perspective on the risk of infertility and fertility preservation options for children and adolescents with sickle cell disease considering hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) performed in children from human leukocyte antigen (HLA)-identical related donors is associated with very high survival rates and disease-free survival. Patients are exposed to gonadotoxic alkylating agents or irradiation in the HCT conditioning regimen. Consequently, infertility is a major long-term complication of HCT for sickle cell disease (SCD). We sought to understand how caregivers perceive the risk of infertility from HCT, how they perceive the options for fertility preservation, and how this risk perception impacted their decision-making to pursue HCT. PROCEDURES: We conducted qualitative interviews with primary caregivers after a consultation for HCT for SCD. Data were analyzed using descriptive qualitative analysis. RESULTS: We interviewed 19 primary caregivers who had attended a consultation with an HCT physician (female, age 25-59 [median 39] years). Eleven participants reported that their child had an available HLA-matched donor. Analysis revealed that (i) mothers were worried about death and graft-versus-host disease from HCT, more than about the risk of infertility; (ii) parents have a realistic understanding of the risk of infertility after HCT and take it into consideration in decision-making; (iii) parents report multiple barriers to fertility preservation. CONCLUSION: For parents actively considering HCT for their child with SCD, the risk of infertility while important was not a barrier to pursuing HCT. Inconvenience and invasiveness of fertility preservation procedures are some of the barriers to pursuing fertility preservation for their child. Future research must aim at addressing these barriers to fertility preservation.

Multimodal phenotyping and correlates of pain following hematopoietic cell transplant in children with sickle cell disease.

INTRODUCTION: There is limited understanding of pain, patient-reported outcomes (PROs) of health-related quality of life (HRQoL), psychological factors, and experimental pain sensitivity before and following hematopoietic cell transplant (HCT) in children with sickle cell disease (SCD). METHODS: Individuals aged 8 years and older, English speaking, and scheduled for a HCT were invited to participate in an observational study where they completed assessments of pain, PROs, psychological factors, and qualitative interviews before and around 3 months, 6 months, 1 year, and 2 years post-HCT. An optional substudy of experimental pain sensitivity before and around 6 month, 1 year, and 2 years post-HCT was also offered. RESULTS: Data from eight participants (median age 13.5 years, 25% female) with sickle cell anemia (SCA) or similarly severe genotype, and successful donor-derived erythropoiesis post-HCT are reported. We found that collection of pain, PROs, psychological factors, and qualitative data were feasible in the context of HCT. We found moderate to large differences in pain and some PROs between baseline to 1 year and baseline to 2 year post-HCT based on effect sizes, but only some differences were statistically significant. We found moderate to large differences in pressure pain threshold and moderate differences in cold pain threshold between baseline to 1 year and baseline to 2 year post-HCT based on effect sizes, but these differences were not statistically significant. Qualitative data indicated an improvement in pain and HRQoL post-HCT. CONCLUSION: This study provides a framework for the conduct of multimodal pain assessments before and after HCT, which is feasible but faced with unique barriers.

Decision-making about gene therapy in transfusion dependent thalassemia.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a treatment option with curative intent for patients with transfusion dependent thalassemia (TDT) but its application is limited by the lack of suitable donors and acceptability due to the related morbidity/mortality. Transplantation of autologous genetically modified hematopoietic cells, gene therapy (GT) is emerging as a promising treatment option for TDT as it eliminates graft versus host disease (GVHD) and need for immunosuppression. Early results of GT suggest that many, but not all patients achieve transfusion independence after the procedure. There is little information about the acceptability of GT in patients with TDT. We sought to examine patient/family knowledge about GT in TDT and to examine factors that influence decision-making about this therapy. METHODS: Parents of children with TDT and adults with TDT were who provided informed consent underwent semi-structured interviews to understand patient/family knowledge and decision-making regarding GT in TDT. Transcribed interviews were coded and the data was examined for emerging themes using a combination of thematic and content analysis. RESULTS: Twenty-five study participants with mean age of 38Y (17-52Y) including eight adults living with TDT, and 17 parents of children with TDT underwent semi-structured qualitative interviews. Participant responses coalesced around broad themes related to knowledge of GT, motivating/deterring factors and outcomes. Study participants expressed a desire for 'cure' from thalassemia including transfusion independence, chelation reduction and improved quality of life as motivators for considering GT. Insufficient knowledge about the process, long-term outcomes, safety, and side effects as well as the potential for death/failure of the procedure were deterrents for the consideration GT. Reduction in frequency of transfusions, even without elimination of transfusions was an acceptable outcome of GT for most participants. Participant choice for preferred treatment modality was split between indefinitely continuing transfusions which was familiar to them versus GT which was unfamiliar, and with an uncertain outcome. None of the participants had a matched sibling donor; alternate donor HSCT was the least preferred option in this group. CONCLUSION: There is tempered excitement about GT in patients/families with TDT with a general willingness to accept transfusions reduction as the outcome.

Characterizing User Engagement With a Digital Intervention for Pain Self-management Among Youth With Sickle Cell Disease and Their Caregivers: Subanalysis of a Randomized Controlled Trial.

BACKGROUND: Sickle cell disease (SCD) is characterized by severe acute pain episodes as well as risk for chronic pain. Digital delivery of SCD pain self-management support may enhance pain self-management skills and accessibility for youth. However, little is known about how youth with SCD and their caregivers engage with digital health programs. iCanCope with pain is a digital pain self-management platform adapted for youth with SCD and caregivers through a user-centered design approach. The program was delivered via a website (separate versions for youth and caregiver) and mobile app (youth only). OBJECTIVE: We aimed to characterize patterns of user engagement with the iCanCope with SCD program among youth with SCD and their caregivers. METHODS: A randomized controlled trial was completed across multiple North American SCD clinics. Eligible youth were aged 12-18 years, diagnosed with SCD, English-speaking, and experiencing moderate-to-severe pain interference. Eligible caregivers were English-speaking with a child enrolled in the study. Dyads were randomized to receive the iCanCope intervention or attention-control education for 8-12 weeks. This report focused on engagement among dyads who received the intervention. User-level analytics were captured. Individual interviews were conducted with 20% of dyads. Descriptive statistics characterized quantitative engagement. Content analysis summarized qualitative interview data. Exploratory analysis tested the hypothesis that caregiver engagement would be positively associated with child engagement. RESULTS: The cohort included primarily female (60% [34/57] of youth; 91% [49/56] of caregivers) and Black (>90% of youth [53/57] and caregivers [50/56]) participants. Among 56 dyads given program access, differential usage patterns were observed: both the youth and caregiver engaged (16/56, 29%), only the youth engaged (24/56, 43%), only the caregiver engaged (1/56, 2%), and neither individual engaged (16/56, 29%). While most youth engaged with the program (40/57, 70%), most caregivers did not (39/56, 70%). Youth were more likely to engage with the app than the website (85% [34/57] versus 68% [23/57]), and the most popular content categories were goal setting, program introduction, and symptom history. Among caregivers, program introduction, behavioral plans, and goal setting were the most popular content areas. As hypothesized, there was a moderate positive association between caregiver and child engagement (χ21=6.6; P=.01; ϕ=0.34). Interviews revealed that most dyads would continue to use the program (11/12, 92%) and recommend it to others (10/12, 83%). The reasons for app versus website preference among youth were ease of use, acceptable time commitment, and interactivity. Barriers to caregiver engagement included high time burden and limited perceived relevance of content. CONCLUSIONS: This is one of the first studies to apply digital health analytics to characterize patterns of engagement with SCD self-management among youth and caregivers. The findings will be used to optimize the iCanCope with SCD program prior to release. TRIAL REGISTRATION: ClinicalTrials.gov NCT03201874; https://clinicaltrials.gov/ct2/show/NCT03201874.

Primary caregiver decision-making in hematopoietic cell transplantation and gene therapy for sickle cell disease.

BACKGROUND: Improved outcomes and the availability of clinical trials of hematopoietic cell transplantation (HCT) from alternate donors and genetically modified autologous hematopoietic progenitor cells have expanded the applicability of HCT for sickle cell disease (SCD). To understand the perspective of primary caregivers exploring HCT in the current milieu, we asked the research question "What motivates primary caregivers to decide to consider HCT and to seek, and to attend, an HCT consultation?" PROCEDURES: We conducted qualitative interviews with primary caregivers within one week after a consultation for HCT for SCD. Data were analyzed using open and axial coding stages of grounded theory methodology. RESULTS: We interviewed 29 primary caregivers (26 females, age 29 to 64 [median 42] years). Primary caregivers report of SCD complications in their child included at least one in the last year by 23 (82%), few or none by 8 (28%), and pain on ≥3 days a week by 13 (46%) primary caregivers. Qualitative analysis revealed that primary caregivers, (i) learn about curative options through social networks, social media, and the news media; (ii) seek consultation because of their child's diminished quality of life, recent complications, an imminent major medical decision, or anxiety about future severe complications; and (iii) see gene therapy as a new, less invasive, and more acceptable treatment. CONCLUSION: Primary caregivers of children with SCD learn about HCT through social networks, social and news media, and explore HCT as a means to prevent SCD complications and help their child live a normal life.

The burden of respiratory syncytial virus infections among children with sickle cell disease.

BACKGROUND: Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. METHODS: We conducted a retrospective, nested, case-control study of children with SCD <18 years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5 years and 5-18 years, respectively. The RSV-related hospitalization rate for children <5 years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8 years vs 7.6 years, P < .001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. CONCLUSION: RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

Educational needs of patients and caregivers living with sickle cell disease results in development of web-based patient decision aid.

AIMS: We performed an assessment to understand perceived decisional needs among those living with sickle cell disease. Additionally, we desired understanding of their preferred methods and quality of learning and sought guidance in development of a web-based patient decision aid. DESIGN: The purpose of this qualitative study was to determine ways patients and caregivers receive education about sickle cell disease and available therapies. We sought to understand preferences for education, quality of current knowledge and information they would like to obtain. METHODS: Recruitment for the initial needs assessment occurred between October 2013 -April 2014. Further recruitment for clarification of internet-based searches occurred between January 2015 -September 2016. We conducted a total of 201 semi-structured qualitative interviews with patients and caregivers. RESULTS: Six themes emerged: healthcare provider education is good but does not meet all the learning needs of the patient/caregiver; patients/caregivers feel a strong desire to seek information about treatment options on their own; adult patients and parents diverged in their core objectives in seeking information: quality of life (QOL) was the major outcome of interest in considering potential treatment options; experience of peers is preferred source for learning about treatment options; and educational needs may be supplemented with a web-based interactive educational tool. CONCLUSION: Patients with sickle cell disease and their caregivers are motivated by a desire to improve QOL in seeking treatment options and use many methods to seek education to supplement what they learn from their healthcare providers and may benefit from the use of a web-based decision aid. Impact Educational needs of patients/caregivers with sickle cell disease were identified and provide the basis to inform the design of educational strategies for them. Nurses and others can assist with learning needs by sharing the website and answering questions that arise.

Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM. METHODS: The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM. RESULTS: Review of 3553 patients (18 039 person-years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin-susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture-positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%). CONCLUSIONS: Distinction between OM and sickle-related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.

Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.

BACKGROUND: Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS: We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS: There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS: Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.

Patient and family experience with chronic transfusion therapy for sickle cell disease: A qualitative study.

BACKGROUND: There is a limited understanding of the patient and family experience of Chronic Transfusion Therapy (CTT) for prevention of complications of Sickle Cell Disease (SCD). We sought to understand patient and family experience with CTT using qualitative methods. METHODS: Fifteen parents of children < 18 years old and nine children 12-18 years old with SCD who were receiving CTT for > 1 year were interviewed using a semi-structured interview format, and interviews were analyzed using open coding methods. RESULTS: Four themes created a narrative of the patient and family experience of CTT: 1) Burden of CTT, 2) Coping with CTT, 3) Perceived benefits and risks of CTT, and 4) Decision making regarding CTT. Participants reported substantial burden of CTT, including the impact of CTT on daily life and family, distress about venous access, burden of chelation therapy, and anxiety about CTT complications. Participants described how they coped with CTT. Participants reported increased energy, decreased pain, fewer hospitalizations, and stroke prevention with CTT, but also recognized complications of CTT, though awareness was limited in adolescents. Parents described sharing in the informed decision-making process with their healthcare provider about CTT, but adolescent patient participants reported that they were not involved in this process. CONCLUSIONS: CTT is associated with significant patient and family burden. Support from family, healthcare providers and school may help individuals cope with some of this burden. These findings provide the basis for future studies to identify strategies to mitigate the burden of CTT and improve the patient experience with this therapy. Future studies should also systematically assess patient knowledge about the key components of CTT and chelation using quantitative assessments.

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study.

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers. Seventeen patients received marrow from an HLA-identical sibling donor and five patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II-III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68%-98%) and 86% (95% CI, 63%-95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).

Incidence of invasive Haemophilus influenzae infections in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for invasive infection with encapsulated bacteria. Antibiotic prophylaxis and immunizations against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) have decreased the overall incidence of invasive infections and have shifted distribution of serotypes causing disease toward those not covered by immunizations. We sought to determine the current incidence of invasive H. influenzae infections in children with SCD and to describe the clinical features and management of these infections. METHODS: Microbiology reports of a large pediatric tertiary care center were reviewed to identify all isolates of H. influenzae detected in sterile body fluid cultures from January 1, 2010 to December 31, 2017. Results were compared with the center's comprehensive clinical database of all children with SCD to identify all cases of children ages 0 to18 years with SCD with invasive H. influenzae disease for the same time period. RESULTS: We captured 2444 patients with SCD, with 14,336 person-years. There were eight episodes of H. influenzae bacteremia in seven children with SCD (five type f, two non-typable, one type a). Most episodes (7 of 8) were in children < 5 years. The incidence rate of invasive H. influenzae in SCD was 0.58/1000 person-years for ages 0 to 18 years and 1.60/1000 person-years for children age < 5 years. There were no deaths from H. influenzae infection. CONCLUSIONS: In the era of universal antibiotic prophylaxis and immunization against Hib, invasive H. influenzae disease due to nonvaccine serotypes remains a risk for children with SCD, particularly those under five years of age.

Comparative Effectiveness of a Web-Based Patient Decision Aid for Therapeutic Options for Sickle Cell Disease: Randomized Controlled Trial.

BACKGROUND: Hydroxyurea, chronic blood transfusions, and bone marrow transplantation are efficacious, disease-modifying therapies for sickle cell disease but involve complex risk-benefit trade-offs and decisional dilemma compounded by the lack of comparative studies. A patient decision aid can inform patients about their treatment options, the associated risks and benefits, help them clarify their values, and allow them to participate in medical decision making. OBJECTIVE: The objective of this study was to develop a literacy-sensitive Web-based patient decision aid based on the Ottawa decision support framework, and through a randomized clinical trial estimate the effectiveness of the patient decision aid in improving patient knowledge and their involvement in decision making. METHODS: We conducted population decisional needs assessments in a nationwide sample of patients, caregivers, community advocates, policy makers, and health care providers using qualitative interviews to identify decisional conflict, knowledge and expectations, values, support and resources, decision types, timing, stages and learning, and personal clinical characteristics. Interview transcripts were coded using QSR NVivo 10. Alpha testing of the patient decision aid prototype was done to establish usability and the accuracy of the information it conveyed, and then was followed by iterative cycles of beta testing. We conducted a randomized clinical trial of adults and of caregivers of pediatric patients to evaluate the efficacy of the patient decision aid. RESULTS: In a decisional needs assessment, 223 stakeholders described their preferences, helping to guide the development of the patient decision aid, which then underwent alpha testing by 30 patients and 38 health care providers and iterative cycles of beta testing by 87 stakeholders. In a randomized clinical trial, 120 participants were assigned to either the patient decision aid or standard care (SC) arm. Qualitative interviews revealed high levels of usability, acceptability, and utility of the patient decision aid in education, values clarification, and preparation for decision making. On the acceptability survey, 72% (86/120) of participants rated the patient decision aid as good or excellent. Participants on the patient decision aid arm compared to the SC arm demonstrated a statistically significant improvement in decisional self-efficacy (P=.05) and a reduction in the informed sub-score of decisional conflict (P=.003) at 3 months, with an improvement in preparation for decision making (P<.001) at 6 months. However, there was no improvement in terms of the change in knowledge, the total or other domain scores of decisional conflicts, or decisional self-efficacies at 6 months. The large amount of missing data from survey completion limited our ability to draw conclusions about the effectiveness of the patient decision aid. The patient decision aid met 61 of 62 benchmarks of the international patient decision aid collaboration standards for content, development process, and efficacy. CONCLUSIONS: We have developed a patient decision aid for sickle cell disease with extensive input from stakeholders and in a randomized clinical trial demonstrated its acceptability and utility in education and decision making. We were unable to demonstrate its effectiveness in improving patient knowledge and involvement in decision making. TRIAL REGISTRATION: ClinicalTrials.gov NCT03224429; https://clinicaltrials.gov/ct2/show/NCT03224429 and ClinicalTrials.gov NCT02326597; https://clinicaltrials.gov/ct2/show/NCT02326597.

Experiences and Decision Making in Hematopoietic Stem Cell Transplant in Sickle Cell Disease: Patients' and Caregivers' Perspectives.

Sickle cell disease (SCD) is one of the most commonly inherited hemoglobin disorders that has a significant impact on quality of life, increased childhood morbidity, and premature mortality. Currently, hematopoietic stem cell transplant (HSCT) is the only treatment with a curative intent. The objective of this study was to determine patients' and caregivers' knowledge of HSCT, the factors influencing the decision to pursue HSCT, their experiences, and the impact of a successful HSCT on their daily living. At Children's Healthcare of Atlanta, we conducted a qualitative study using a semistructured interview guide of patient-caregiver dyads and 2 focus-group sessions of adult long-term survivors of HSCT to elicit key factors in decision making, their experiences with HSCT, and the impact of HSCT. Interviews and focus-group sessions were recorded and transcribed verbatim. Transcripts were coded and analyzed for emerging themes using NVivo 10.0. We enrolled 11 patient-caregiver dyads (n = 6, female patients; n = 10, mothers) in the qualitative interviews and 2 focus groups with 5 (n = 2, females) and 7 (n = 3, females) participants in each group, respectively. Our analysis revealed 3 prominent themes: (1) factors and concerns influencing HSCT decision making; (2) HSCT experiences; and (3) impact of HSCT on daily life. Participants reported that progression of disease-related complications and availability of a matched donor strongly influenced the decision to pursue HSCT. Although patients and caregivers had to deal with the arduous process of HSCT and transplant-related morbidities, participants were satisfied with their decision and expressed no decisional regrets. Decision making for HSCT for patients with SCD is a complex process. Understanding the key influential factors in decision making and the impact HSCT has on these patients and their families will generate crucial insights that can guide the care of future patients and research studies.

A cognitive-behavioral digital health intervention for sickle cell disease pain in adolescents: a randomized, controlled, multicenter trial.

ABSTRACT: Severe acute and chronic pain are the most common complications of sickle cell disease (SCD). Pain results in disability, psychosocial distress, repeated clinic visits/hospitalizations, and significant healthcare costs. Psychosocial pain interventions that teach cognitive and behavioral strategies for managing pain have been effective in other adolescent populations when delivered in person or through digital technologies. Our aim was to conduct a multisite, randomized, controlled trial to improve pain and coping in youth aged 12 to 18 years with SCD using a digital cognitive-behavioral therapy program (iCanCope with Sickle Cell Disease; iCC-SCD) vs Education control. We enrolled 137 participants (ages 12-18 years, 59% female) and analyzed 111 adolescents (107 caregivers), 54 randomized to Education control and 57 randomized to iCC-SCD. Ninety-two percent of youth completed posttreatment assessments and 88% completed 6-month follow-up. There was a significant effect of treatment group (iCC-SCD vs Education) on reduction in average pain intensity from baseline to 6-month follow-up (b = -1.32, P = 0.009, 95% CI [-2.29, -0.34], d = 0.50), and for the number of days with pain, adolescents in the iCC-SCD group demonstrated fewer pain days compared with the Education group at 6-month follow-up (incident rate ratio = 0.63, P = 0.006, 95% CI [0.30, 0.95], d = 0.53). Treatment effects were also found for coping attempts, momentary mood, and fatigue. Several secondary outcomes did not change with intervention, including anxiety, depression, pain interference, and global impression of change. Future studies are needed to identify effective implementation strategies to bring evidence-based cognitive-behavioral therapy for sickle cell pain to SCD clinics and communities.

High-impact chronic pain in sickle cell disease: insights from the Pain in Sickle Cell Epidemiology Study (PiSCES).

ABSTRACT: The US National Pain Strategy recommends identifying individuals with chronic pain (CP) who experience substantial restriction in work, social, or self-care activities as having high-impact chronic pain (HICP). High-impact chronic pain has not been examined among individuals with CP and sickle cell disease (SCD). We analyzed data from 63 individuals with SCD and CP who completed at least 5 months of pain diaries in the Pain in Sickle Cell Epidemiology Study (PiSCES). Forty-eight individuals met the definition for HICP, which was operationalized in this study as reporting pain interference on more than half of diary days. Compared with individuals without HICP, individuals with HICP experienced higher mean daily pain intensity, particularly on days without crises. They also experienced a greater proportion of days with pain, days with healthcare utilization, and days with home opioid use and higher levels of stress. They did not have a statistically significantly higher proportion of days with crises or experience higher mean daily pain intensity on days with crises. Individuals with HICP experienced worse physical functioning and worse physical health compared with those without HICP, controlling for mean pain intensity, age, sex, and education. The results of this study support that HICP is a severely affected subgroup of those with CP in SCD and is associated with greater pain burden and worse health outcomes. The findings from this study should be confirmed prospectively in a contemporary cohort of individuals with SCD.

Sex and frequency of pain episodes are associated with acute pain trajectories in adolescents with sickle cell disease.

Introduction/Objective: Acute pain episodes are a major cause of health care utilization (HCU) in sickle cell disease (SCD), and adolescence is associated with increased pain frequency. We sought to determine whether there were differences in acute pain trajectories by sex and frequency of pain episodes among adolescents with SCD who presented to the emergency department (ED). Methods: Retrospective review of electronic health records from a large, multicampus, pediatric SCD program. Results: Of the 113 adolescents included, the mean age was 16.6 (SD 0.9), 41.6% (n = 47) were female, 77.9% (n = 88) had HbSS or a similarly severe genotype, and 43.4% (n = 49) had ≥3 episodes of HCU for pain, which we defined as having history of high HCU for pain. Those with a history of high HCU for pain had higher mean pain intensity scores at presentation, were more likely to receive either intravenous or intranasal opioids, and were more likely to be hospitalized. In a model considering the 3-way interaction between sex, history of high HCU for pain, and follow-up time from the initial pain intensity score, adjusted for opioid per kilogram body weight, and prescription of hydroxyurea, adolescent female patients with high HCU for pain had the slowest decline in pain intensity during treatment for acute pain in the ED. Conclusion: Sex and history of high HCU for pain are associated with acute pain trajectories in adolescents with SCD presenting to the ED. These novel findings should be confirmed in future prospective studies.