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.

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.

A Decision Support Tool for Allogeneic Hematopoietic Stem Cell Transplantation for Children With Sickle Cell Disease: Acceptability and Usability Study.

BACKGROUND: Individuals living with sickle cell disease (SCD) may benefit from a variety of disease-modifying therapies, including hydroxyurea, voxelotor, crizanlizumab, L-glutamine, and chronic blood transfusions. However, allogeneic hematopoietic stem cell transplantation (HCT) remains the only nonexperimental treatment with curative intent. As HCT outcomes can be influenced by the complex interaction of several risk factors, HCT can be a difficult decision for health care providers to make for their patients with SCD. OBJECTIVE: The aim of this study is to determine the acceptability and usability of a prototype decision support tool for health care providers in decision-making about HCT for SCD, together with patients and their families. METHODS: On the basis of published transplant registry data, we developed the Sickle Options Decision Support Tool for Children, which provides health care providers with personalized transplant survival and risk estimates for their patients to help them make informed decisions regarding their patients' management of SCD. To evaluate the tool for its acceptability and usability, we conducted beta tests of the tool and surveys with physicians using the Ottawa Decision Support Framework and mobile health app usability questionnaire, respectively. RESULTS: According to the mobile health app usability questionnaire survey findings, the overall usability of the tool was high (mean 6.15, SD 0.79; range 4.2-7). According to the Ottawa Decision Support Framework survey findings, acceptability of the presentation of information on the decision support tool was also high (mean 2.94, SD 0.63; range 2-4), but the acceptability regarding the amount of information was mixed (mean 2.59, SD 0.5; range 2-3). Most participants expressed that they would use the tool in their own patient consults (13/15, 87%) and suggested that the tool would ease the decision-making process regarding HCT (8/9, 89%). The 4 major emergent themes from the qualitative analysis of participant beta tests include user interface, data content, usefulness during a patient consult, and potential for a patient-focused decision aid. Most participants supported the idea of a patient-focused decision aid but recommended that it should include more background on HCT and a simplification of medical terminology. CONCLUSIONS: We report the development, acceptability, and usability of a prototype decision support tool app to provide individualized risk and survival estimates to patients interested in HCT in a patient consultation setting. We propose to finalize the tool by validating predictive analytics using a large data set of patients with SCD who have undergone HCT. Such a tool may be useful in promoting physician-patient collaboration in making shared decisions regarding HCT for SCD. Further incorporation of patient-specific measures, including the HCT comorbidity index and the quality of life after transplant, may improve the applicability of the decision support tool in a health care setting.

Iron depletion attenuates steatosis in a mouse model of non-alcoholic fatty liver disease: Role of iron-dependent pathways.

BACKGROUND & AIMS: Iron has been proposed as influencing the progression of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD). We have previously shown that, in the Hfe-/- mouse model of hemochromatosis, feeding of a high-calorie diet (HCD) leads to increased liver injury. In this study we investigated whether the feeding of an iron deficient/HCD to Hfe-/- mice influenced the development of NAFLD. METHODS: Liver histology was assessed in Hfe-/- mice fed a standard iron-containing or iron-deficient diet plus or minus a HCD. Hepatic iron concentration, serum transferrin saturation and free fatty acid were measured. Expression of genes implicated in iron regulation and fatty liver disease was determined by quantitative real-time PCR (qRT-PCR). RESULTS: Standard iron/HCD-fed mice developed severe steatosis whereas NAS score was reduced in mice fed iron-deficient HCD. Mice fed iron-deficient HCD had lower liver weights, lower transferrin saturation and decreased ferroportin and hepcidin gene expression than HCD-fed mice. Serum non-esterified fatty acids were increased in iron-deficient HCD-fed mice compared with standard iron HCD. Expression analysis indicated that genes involved in fatty-acid binding and mTOR pathways were regulated by iron depletion. CONCLUSIONS: Our results indicate that decreasing iron intake attenuates the development of steatosis resulting from a high calorie diet. These results also suggest that human studies of agents that modify iron balance in patients with NAFLD should be revisited.

A pilot study of the acceptability, feasibility and safety of yoga for chronic pain in sickle cell disease.

OBJECTIVES: To determine the acceptability, feasibility and safety of yoga for chronic pain in sickle cell disease. DESIGN AND SETTING: In Part A of this two-part study, adolescents with SCD and chronic pain (Group 1) and their parent (Group 2) completed a survey designed to capture pain characteristics, attitudes and practices related to yoga, and potential acceptability of a yoga program. In Part B, the study assessed the feasibility and safety of an instructor-led group yoga program. The study was registered on clinicaltrials.gov (NCT03694548). INTERVENTION: Eight instructor-led group yoga sessions. MAIN OUTCOME MEASURES: Feasibility and safety outcomes were chosen a priori, as follows: 1) Proportion of adolescent patients with SCD and chronic pain approached that consent to participate in Part A, 2) Proportion of adolescent participants enrolled in Part A that consent to participate in Part B, 3) Proportion of participants enrolled in Part B that attend at least 6 of 8 yoga sessions, 4) Proportion of participants enrolled in Part B with an ED visit or a hospitalization for pain within 24 h of completion of each yoga session, 5) Proportion of participants in Part B who complete all study assessments before, and at the end of the yoga program, 6) Adherence to submission of pain diary. RESULTS: The median age of 15 patient participants in Part A was 16 (IQR 14-17), and 14 parents was 43.5 (IQR 42-51). Most participants were female. Most participant responses indicated a positive opinion of yoga. Nine adolescents (60 %) from Part A participated in Part B of the study. The median age of 9 participants in Part B was 17 (IQR 15-18), and 5 of the 9 participants were female (53.3 %). Only one participant was able to attend 3 of the 8 yoga sessions offered, and did not experience any ED visits or hospitalizations following the yoga sessions. None of the other feasibility endpoints were met in this study. CONCLUSIONS: Patients with SCD and chronic pain overall have a positive opinion of yoga, but there are challenges with recruitment and retention of participants in a clinical trial of yoga, and barriers to feasibility of an in-person group yoga intervention.

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.

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.

Patient Perspectives on Short-Course Pharmacotherapy: Barriers and Facilitators to Medication Adherence.

BACKGROUND: Medication nonadherence is a public health issue that contributes to poor health outcomes and health-care costs. Factors influencing long-term medication adherence are known; however, little is known about short-course medication adherence. OBJECTIVE: This study examined patient perspectives on adherence and factors that influence adherence to short-course pharmacotherapy in diarrhea-predominant irritable bowel syndrome. METHOD: Twenty-seven participants were interviewed to identify their perceptions of barriers and facilitators to thrice-daily, 14-day rifaximin. RESULTS: Participants were primarily female (89%), aged 18 to 65 years. Sixty-eight percent of interviewees were identified as "low-adherers," meaning the percentage of days with correct daily dosing of rifaximin was <80%. The final coding framework identified social/economic-related (family support and medication expense), system-related (relationship with provider and medication knowledge), condition-related (symptom severity), therapy-related (inconvenient dosing), and patient-related (forgetfulness and busyness of daily life) factors that influenced adherence. CONCLUSION: The resulting patient perspectives highlight a diverse set of factors that influence short-course adherence and the need for tailored interventions that address these various factors resulting in enhanced patient outcomes.

Assessment of Patient and Caregiver Attitudes and Approaches to Decision-Making Regarding Bone Marrow Transplant for Sickle Cell Disease: A Qualitative Study.

Importance: Bone marrow transplant (BMT) is a potentially curative treatment for sickle cell disease (SCD). Patient and caregiver attitudes toward BMT for SCD and the willingness to accept risks of BMT vary, but these attitudes are not well understood. Objective: To understand patient and caregiver perceptions of and attitudes toward BMT for SCD and decision-making about BMT. Design, Setting, and Participants: Qualitative study of interview transcripts from a convenience sample. Transcripts were from adults with SCD and caregivers of patients with SCD recruited from national and regional SCD conferences, symposia, and sickle cell clinics in 2 cities. Interview transcripts were used from the needs assessment phase to develop a patient-decision aid in 2013 to 2014 (group 1) and from the baseline point in 2015 to 2016 (group 2) of the parent trial, a randomized clinical trial of adults and caregivers of patients with SCD to evaluate the effectiveness of a patient decision aid. Main Outcomes and Measures: Participant perspectives on decision-making regarding BMT for SCD. Results: Fifty-seven transcripts from adults with SCD and 50 transcripts from caregivers of patients with SCD were included. Median (interquartile range [IQR]) age of adults with SCD was 34 (21-50) years in group 1 and 30 (23-38) years in group 2. The median (IQR) age of caregivers was 42.5 (31-52) years in group 1 and 41 (35-46.5) years in group 2. Most transcripts from adults with SCD (75.0% in group 1 and 72.4% in group 2) and caregivers of patients with SCD (76.7% in group 1 and 85.0% in group 2) were from female participants. Bone marrow transplant was perceived as a treatment option associated with serious risks. Reported attitudes toward BMT occurred on a continuum ranging from unfavorable to favorable. Participants reported serious decisional dilemma regarding BMT for SCD. Most participants expressed interest in learning about BMT or curative treatments. Conclusions and Relevance: This qualitative study found a continuum in attitudes toward BMT for SCD and highlights the complexity of decision-making in BMT for SCD. Patients and families with SCD expressed an interest in learning about BMT. Future prospective studies of patient decision-making regarding BMT, especially in the context of emerging curative and novel disease-modifying therapies for SCD, are warranted.

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.

A dual efficacy-implementation trial of a novel mobile application for childhood nephrotic syndrome management: the UrApp for childhood nephrotic syndrome management pilot study protocol (UrApp pilot study).

BACKGROUND: Idiopathic nephrotic syndrome has a relapsing-remitting course in the majority of pediatric patients, demanding vigilant monitoring and self-management. A novel, expert-designed, user-informed mobile application (app), UrApp©, was created to support management tasks, including home urine protein monitoring. METHODS: The UrApp Pilot Study (ClinicalTrials.gov, NCT04075656) is a randomized trial comparing UrApp-supported nephrotic syndrome management with standard-of-care with parallel process evaluation of the intervention delivery. Sixty caregivers of children with newly diagnosed, steroid-sensitive nephrotic syndrome will be randomized 1:1 to UrApp-supported care or standard-of-care. Follow-up will be 1 year, with primary outcomes of adherence to urine monitoring and medications assessed at 6 and 12 months. Secondary outcomes at 6 and 12 months include self-efficacy, quality-of-life, hospitalizations and delayed relapse diagnoses. A mixed-methods approach will evaluate UrApp engagement, use retention, features used, user perceptions, and contextual barriers and facilitators of UrApp use. User behavior will be assessed for relationships to the primary and secondary outcomes. A Stakeholder Committee of volunteer trial participants, clinicians, and engineers will examine the trial results and design a pragmatic UrApp-enhanced nephrotic syndrome intervention with potential for wide implementation. The final UrApp intervention will be tested in a user-centered hybrid effectiveness-implementation trial designed with stakeholder input. DISCUSSION: The UrApp Pilot Study examines the efficacy of a novel app designed specifically for nephrotic syndrome. The protocol involves dual efficacy and process evaluation aims to increase efficiency and incorporates the stakeholders' perspective in formative assessment to inform intervention redesign and the design of a future user-centered trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04075656. Registered on September 2, 2019, https://clinicaltrials.gov/ct2/show/NCT04075656.

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.

Management of Chronic Pain in Adults Living With Sickle Cell Disease in the Era of the Opioid Epidemic: A Qualitative Study.

Importance: The hallmark of sickle cell disease (SCD) is vaso-occlusive pain that may be acute and episodic or may progress to chronic, persistent pain with unpredictable and disabling exacerbations. Patients with SCD rely on opioids almost exclusively for acute and chronic pain management. Objective: To understand how the current opioid epidemic and subsequent guidelines from the Centers for Disease Control and Prevention are associated with the management of acute and chronic pain for patients with SCD. Design, Setting, and Participants: Qualitative study using semistructured interview guides. Interviews 1 hour or longer were conducted over the telephone. Participants were adults (aged ≥18 years) diagnosed with SCD who experienced pain on 3 or more days per week recruited from national SCD conferences, symposiums, and 2 sickle cell clinics. Open coding analysis facilitated thematic analysis of interview transcripts. Data collection took place from May 2017 to June 2018. Main Outcomes and Measures: Participant perspective of any changes to their pain management associated with the 2016 guidelines from the Centers for Disease Control and Prevention. Results: The 15 adults interviewed had a median (range) age of 32 (21-52) years; 13 (87%) were female; and all were of African American race/ethnicity. Participants reported that recently their opioid prescriptions had become more restrictive, were more closely monitored, and were increasingly difficult to fill in pharmacies. Participants also described increased stigmatization about opioid use and that their medical care was being affected by the physician's exclusive focus on reducing pain medication use. There was an emerging interest among adult patients in the consideration of the use of alternative therapies, including marijuana, to manage pain. Conclusions and Relevance: These findings suggest that from the perspective of adults living with SCD, the opioid epidemic may have negatively affected patients' care by increasing barriers to opioids. Patients reported decreased opioid dosing, increased stigmatization regarding opioid use, physician preoccupation with opioid dosage interfering with comprehensive care, and lack of access to alternative therapies.

A Qualitative Study of Chronic Pain and Self-Management in Adults with Sickle Cell Disease.

Acute, intermittent vaso-occlusive pain is the hallmark of sickle cell disease (SCD) and is associated with substantial morbidity and impaired quality of life (QOL). The subgroup of adults with SCD who transition from recurrent, acute pain to chronic, persistent pain have even greater QOL impairment and higher rates of healthcare utilization. Self-management is central to SCD management; however, its role in chronic pain management is not established. This qualitative study was conducted to answer the following research questions: (1) What is the chronic pain experience of adults with SCD? (2) What self-management strategies do adults with SCD use for chronic pain? and (3) Do adults with SCD have any needs in the self-management of chronic pain? Eighteen Black adults with SCD completed a demographics questionnaire and an interview. The majority of the participants were 21-30 years of age (mean 33.5, SD 7.6), female (61.1%), employed at least part-time (61.1%), single/never married (72.2%), and had a SCD type of sickle cell anemia (55.5%). Interview analysis revealed three major themes: (1) the chronic pain experience; (2) strategies for managing chronic pain; and (3) challenges and needs in managing chronic pain. Study findings can be used to support chronic pain management among adults with SCD. Further research is needed to devise and implement effective strategies for the prevention and management of chronic SCD pain.

From trust to skepticism: An in-depth analysis across age groups of adults with sickle cell disease on their perspectives regarding hydroxyurea.

Despite its efficacy, the uptake of HU in adults with sickle cell disease (SCD) is poor likely due to a combination of system, provider, and patient-related factors. We investigated attitudes of adult patients towards HU by conducting qualitative interviews with 95 adult SCD patients (age 18 to 67 years old, 71 were female). While 53% of all participants reported that they were currently taking HU, patients ranging in age 18-30 years (Group 1) were more likely to report current HU use as compared to those (Group 2) ranging in age 31-67 years (65% vs. 41% P = 0.01). Most Group 1 participants who reported currently taking HU indicated that the decision to start HU was made by a parent, though some made the decision themselves as a young adult. Group 1 participants expressed trust in the efficacy of HU as well as trust that their physician adequately shared risks and benefits for the medication. The Group 2 participants, who were not currently on HU, were skeptical that all the risks and benefits of HU were known, were concerned that the efficacy of HU was not proven, and that they were not receiving complete information about its potential side effects. Of Group 2 participants who reported currently being on HU, 25% were concerned about the side effects and efficacy of HU and reported continuing HU because of a lack of effective alternatives. These data suggest that there are significant differences by age in adult SCD patients' attitudes towards, utilization and understanding of the risks and benefits of HU.

Presence of pain on three or more days of the week is associated with worse patient reported outcomes in adults with sickle cell disease.

While acute episodic pain is the hallmark of sickle cell disease (SCD), transition to chronic pain is a major cause of morbidity and impaired quality of life. One of the core diagnostic criteria used by Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT) to define chronic SCD pain is the presence of pain on a "majority of days" in the past 6 months in one or more locations. The frequency characteristic of "majority of days" is adapted from the criteria of 15 days or more per month, used to define chronic migraine, but there are inadequate data to support this cutoff in SCD. Using an existing dataset of adults with SCD who completed patient-reported outcomes of pain interference, physical functioning, anxiety, depression, and fatigue using the National Institutes of Health (NIH) patient-reported outcomes measures information system (PROMIS) short-form instruments, we examined the association of the presence of pain on 3 or more days per week with patient-reported outcomes of functioning. In unadjusted analyses, presence of pain on 3 or more days a week was associated with higher median PROMIS scores of pain interference, anxiety, and depression. Median PROMIS scores of fatigue and physical function were worse in women compared with men in unadjusted analyses. We did not find any difference in median PROMIS pain scores between adults aged ≤35 years compared with those aged ≥35 years. In linear regression models, after adjustment for age and sex, the presence of pain on 3 or more days a week was found to be associated with worse pain interference and anxiety. These data support the clinical relevance of the frequency characteristic of pain on a "majority of days" in the definition of chronic SCD pain, and provide the rationale for prospective studies to validate the clinical definition of chronic pain in SCD.

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.

Proponent or collaborative: Physician perspectives and approaches to disease modifying therapies in sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider. While previous research has focused on the patient perspective of treatment-related decision making, there is a paucity of research investigating the physician perspective of treatment-related decision making. We conducted a qualitative study with physicians who were experts in the field of SCD. Interviews focused on physician perceptions of patient decisional needs as well as physicians' approach to decision making regarding disease-modifying therapies in SCD. Thirty-six physician interviews were analyzed, with a focus on their perspectives regarding available treatment options and on how they approach decision making with patients. We identified two narrative approaches. The Collaborative approach (CA) was characterized by emphasizing the need to discuss all possible treatment options to ensure that the patient and/or family was equipped to make an informed decision. The Proponent approach (PA) was characterized by strongly advocating a pre-determined treatment plan and providing patients/families with information, with the objective of convincing them to accept the treatment. An interplay of patient-related and disease-related factors, decision type and physician-related factors, as well as institutional frameworks, influenced physician perspectives on treatment options and decision making regarding these therapies. These findings point to the potential value of developing systems to foster patient engagement as a way of facilitating shared decision making.

Novel Metrics in the Longitudinal Evaluation of Pain Data in Sickle Cell Disease.

BACKGROUND: Available modalities for the longitudinal capture and analysis of pain intensity in patients with sickle cell disease (SCD) limit our ability to study intraindividual and interindividual variation in pain and the factors influencing the transition from acute to chronic pain in patients with SCD. OBJECTIVES: The objectives of this study were to determine the feasibility of electronic capture of longitudinal outpatient pain intensity data and to test the applicability of novel metrics in the study of intraindividual and interindividual variation in pain in patients with SCD. MATERIALS AND METHODS: Twenty SCD patients aged 13 to 21 submitted 2045 diary days of pain intensity data over 229 days using a web-based electronic pain diary or through text message. RESULTS: Participants reported pain (11-point Numerical Rating Score >0) on 1559 diary days (76.2%) suggesting a significant outpatient pain burden. In addition to mean maximum daily pain (MMDP), using maximum daily pain (MDP) scores, we calculated the ninetieth percentile (p90) of MDP, proportion of pain-free days (PPFD), Standard Deviation (SD) of MDP and coefficient of variation (CV) of MDP. Although p50 of MDP and p90 of MDP correlated positively with MMDP, PPFD correlated negatively with MMDP and both MMDP and PPFD correlated poorly with the SD of MDP. Examination of graphic representation of pain trends demonstrated how patients with similar MMDP had varying p90, PPFD, SD/coefficient of variation, and ultimately burden of pain over time. Missing data rates were lowest in the first 30 days of reporting and increased over time. Study participants reported a positive experience with momentary pain reporting and improved communication with health care providers regarding pain. CONCLUSIONS: The longitudinal collection of pain data with the inclusion of hospital data during periods of hospitalization is feasible and acceptable in patients with SCD over periods of 30 to 60 days. Long-term collection of pain diary data, while informative, is associated with higher rates of missing data. Novel metrics of pain have the potential to better describe intraindividual and interindividual variation in pain, inform studies of the transition from acute to chronic pain as well as contribute patient-reported end points of pain for interventional clinical trials of pain in SCD.

Hydroxyurea therapy for children with sickle cell disease: describing how caregivers make this decision.

BACKGROUND: Hydroxyurea (HU) is underutilized in children with sickle cell disease (SCD) because caregivers frequently decline HU when it is offered. This study explores what impacts this decision. RESULTS: Caregivers of children with clinically severe SCD whose children were offered HU previously were interviewed. We used a qualitative analytical approach to analyze their telephone interview transcripts. Caregivers who chose HU (n = 9) reported their children had severe SCD, sought detailed information about HU, and accepted HU as a preventative therapy. In contrast, caregivers who did not choose HU (n = 10) did not perceive their children as having severe SCD and did not question their child's provider about HU. CONCLUSIONS: This study identifies specific areas that providers should address to when they discuss HU with families so that they can make informed decisions. Our study also uncovered factors that are important to consider when designing future interventions to improve hydroxyurea acceptance and when developing decision-aid tools to assist caregivers of children with SCD who are considering disease modifying therapies.