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Objective Population-level data on sickle cell disease (SCD) are sparse in the United States. The Centers for Disease Control and Prevention (CDC) is addressing the need for SCD surveillance through state-level Sickle Cell Data Collection Programs (SCDC). The SCDC developed a pilot common informatics infrastructure to standardize processes across states. Materials and Methods We describe the process for establishing and maintaining the proposed common informatics infrastructure for a rare disease, starting with a common data model and identify key data elements for public health SCD reporting. Results The proposed model is constructed to allow pooling of table shells across states for comparison. Core Surveillance Data reports are compiled based on aggregate data provided by states to CDC annually. Discussion and Conclusion We successfully implemented a pilot SCDC common informatics infrastructure to strengthen our distributed data network and provide a blueprint for similar initiatives in other rare diseases.

BACKGROUND: Adolescent and young adult (AYA) women with sickle cell disease (SCD) have increased pregnancy-related health risks and are prescribed potentially teratogenic medications, yet limited data are available regarding pediatric SCD provider contraceptive practices. We aimed to assess pediatric hematology providers’ beliefs, practices, motivators, and barriers for providing contraceptive care to female AYA with SCD. METHODS: Guided by the Health Belief Model (HBM), we developed a 25-question, web-based survey to assess practices. Survey links were distributed nation-wide to pediatric SCD and/or general hematology providers through their publicly available emails and by request to directors of U.S. accredited Pediatric Hematology-Oncology fellowship programs for distribution to their SCD providers. Data analysis included descriptive statistics, chi-square analysis, logistic regression. RESULTS: Of 177 respondents, 160 surveys meeting inclusion criteria were analyzed. Most providers reported counseling (77.5%) and referring female AYA patients for contraception (90.8%), but fewer reported prescribing contraception (41.8%). Proportionally fewer trainees provided counseling compared to established providers (54% vs. 85%, p

Background:The management of acute and chronic pain for individuals living with sickle cell disease (SCD) is a clinical challenge. This reflects the paucity of clinical SCD pain research and limited understanding of the complex biological differences between acute and chronic pain. These issues collectively create barriers to effective, targeted interventions. Optimal pain management requires interdisciplinary care.Objective:These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD.Methods:ASH formed a multidisciplinary panel, including 2 patient representatives, that was thoroughly vetted to minimize bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic reviews. Clinical questions and outcomes were prioritized according to importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment.Results:The panel reached consensus on 18 recommendations specific to acute and chronic pain. The recommendations reflect a broad pain management approach, encompassing pharmacological and nonpharmacological interventions and analgesic delivery.Conclusions:Because of low-certainty evidence and closely balanced benefits and harms, most recommendations are conditional. Patient preferences should drive clinical decisions. Policymaking, including that by payers, will require substantial debate and input from stakeholders. Randomized controlled trials and comparative-effectiveness studies are needed for chronic opioid therapy, nonopioid therapies, and nonpharmacological interventions.

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

PURPOSE To evaluate different T2 -oxygenation calibrations for estimating venous oxygenation in people with sickle cell anemia (SCA). METHODS Blood T2 values were measured at 3 T in the internal jugular veins of 12 healthy volunteers and 11 SCA participants with no history of stroke, recent transfusion, or renal impairment. T2 -oxygenation relationships of both sickled and normal blood samples were calibrated individually and compared with values generated from published models. After converting venous T2 values to venous oxygenation, whole-brain oxygen extraction fraction and cerebral metabolic rate of oxygen were calculated. RESULTS Sickle blood samples' oxygenation values calculated from our individual calibrations agreed well with measurements using a blood analyzer, whereas previous T2 calibrations based on normal blood samples showed 13%-19% underestimation. Meanwhile, oxygenation values calculated from previous grouped T2 calibration for sickle blood agreed well with experimental measurement on averaged values, but showed up to 20% variation for several individual samples. Using individual T2 calibrations, the whole-brain oxygen extraction fraction and cerebral metabolic rate of oxygen of SCA participants were 0.38 ± 0.08 and 172 ± 42 µmol/min/100 g, respectively, which were comparable to those values measured on healthy volunteers. CONCLUSION Our results confirm that sickle blood T2 values not only depend on the hematocrit and oxygenation values, but also on other hematological factors. The individual T2 calibrations minimized the effect of heterogeneity of sickle blood between different SCA populations and improved the accuracy of T2 -based oximetry. The measured oxygen extraction fraction and cerebral metabolic rate of oxygen of this group of SCA participants were found to not differ significantly from those of healthy individuals.

Introduction Sickle cell disease (SCD) is the most common abnormal genetic blood disease that affects ∼100,000 Americans. Approximately 20% to 37% of children with sickle cell anemia have silent cerebral infarcts by the age of 14 years old. Neurocognitive deficits are identified in infants and preschool children with SCD. The purpose of this systematic literature review is to provide a comprehensive understanding of the prevalence, severity, and the associated risk factors for neurodevelopmental delays (NDDs) in children with SCD 5 years of age and younger. Methods Systematic search of 6 databases identified 2467 potentially relevant publications and 8 were identified through a manual search. Only 24 articles met the inclusion criteria. Results We identified an increased prevalence of NDDs (cognitive, motor, or both). Children experienced deficits with language, attention and behavior, executive functioning, school readiness and/or academic performance, and motor skills (fine and gross motor functioning). Risk factors include silent cerebral infarcts and strokes, SCD genotype (HbSS>HbSC), other biological, and social factors. Conclusion NDDs are common in children ages 0 to 5 years old with SCD. There is an opportunity to improve adherence to national guideline recommendations and early detection practices by pediatricians, hematologists, and other health care providers.

The life-limiting and unpredictable nature of sickle cell disease (SCD) is well-established, yet there is limited literature on end-of-life planning. The purpose of this study was to describe perspectives about preparing for death for older adults with SCD. We enrolled 19 older adults with SCD (age ≥ 50 years) into this qualitative descriptive study. Theme 1 was “anticipation of early death,” with sub-themes: (a) informed of early death and (b) making plans for death. Theme 2 was “near death experiences.” Theme 3 was “differences in level of comfort with death” with subthemes: (a) death as a part of life and (b) differences in level of comfort discussing death. Theme 4 was “influence of spirituality” with subthemes: (a) God controls the timing of death and (b) belief in the afterlife. These results will inform interventions to improve the quality of patient-provider communication to provide goal-concordant end-of-life care for adults with SCD.

Background The life expectancy for people with sickle cell disease (SCD) has improved tremendously over the last 50 years. This population experiences hemolysis and vaso-occlusion in multiple organs that lead to complications such as cardiopulmonary disease, strokes, and avascular necrosis. These complications can limit mobility and aerobic endurance, similar to limitations that often occur in geriatric populations. These sickle-cell and age-related events lead to frequent hospitalization, which further increases the risk of functional decline. We have few tools to measure functional decline in people with SCD. The purpose of this paper is to describe a protocol to evaluate the feasibility of sickle cell disease geriatric assessment (SCD-GA). Methods/design We will enroll 40 adults with SCD (20 age 18–49.99 years and 20 age ≥ 50 years) in a prospective cohort study to assess the feasibility of SCD-GA. The SCD-GA includes validated measures from the oncology geriatric assessment enriched with additional physical and cognitive measures. The SCD-GA will be performed at the first study visit, at 10 to 20 days after hospitalization, and at 12 months (exit visit). With input from a multidisciplinary team of sickle cell specialists, geriatricians, and experts in physical function and physical activity, we selected assessments across 7 domains: functional status (11 measures), comorbid medical conditions (1 measure), psychological state (1 measure), social support (2 measures), weight status (2 measures), cognition (3 measures), and medications (1 measure). We will measure the proportion completing the assessment with feasibility as the primary outcome. Secondary outcomes include the proportion consenting and completing all study visits, duration of the assessment, acceptability, and adverse events. Discussion We present the protocol and rationale for selection of the measures included in SCD-GA. We also outline the methods to determine feasibility and subsequently to optimize the SCD-GA in preparation for a larger multicenter validation study of the SCD-GA.

BackgroundStudies of interventions to prevent the many neurological complications of sickle cell disease must take into account multiple outcomes of variable severity, with limited sample size. The goals of the studies presented were to use investigator preferences across outcomes to determine an attitude-based weighting of relevant clinical outcomes and to establish a valid composite outcome for a clinical trial.MethodsIn Study 1, investigators were surveyed about their practice regarding hydroxyurea therapy and opinions about outcomes for the “Hydroxyurea to Prevent the Central Nervous System Complications of Sickle Cell Disease Trial” (HU Prevent), and their minimally acceptable relative risk reduction for the two outcome components, motor and neurocognitive deficits. In Study 2, HU Prevent investigators provided overall weights for these two components. In Study 3, they provided more granular rankings, ratings, and maximum number acceptable to harm. A weighted composite outcome, the Stroke Consequences Risk Score, was constructed that incorporates the major neurologic complications of sickle cell disease. The Stroke Consequences Risk Score represents the 3-year risk of suffering the adverse consequences of stroke. In Study 4, the results of the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP2) and Silent Infarct Transfusion Trials were reanalyzed in light of the composite outcome.ResultsIn total, 22 to 27 investigators participated per study. In Study 1, across three samplings between 2009 and 2015, the average minimally acceptable relative risk reduction ranged from 0.36 to 0.50, at or below the target effect size of 0.50. In 2015, 21 (91%) reported that a placebo-controlled trial is reasonable; 23 (100%), that it is ethical; and 22 (96%), that they would change their practice, if the results of the trial were positive. In Studies 2 and 3, the weight elicited for a cognitive decline (of 10 IQ points) from the overall assessment was 0.67 (and for motor deficit, the complementary 0.33); from ranking, 0.6; from rating, 0.58; and from maximal number acceptable to harm, 0.5. Using data from two major clinical trials, Study 4 demonstrated the same conclusions as the original trials using the Stroke Consequences Risk Score, with smaller p-values for both reanalyses. An assessment of acceptability was performed as well.ConclusionThis set of studies provides the rationale, justification, and validation for the use of a weighted composite outcome and confirms the need for the phase III HU Prevent study. Surveys of investigators in multi-center studies can provide the basis of clinically meaningful outcomes that foster the translation of study results into practice while increasing the efficiency of a study.

Introduction: Sickle cell disease (SCD) is the most common hemoglobinopathy in the world and it disproportionately affects population in tropical, resource-constrained regions where there is a high prevalence of malaria. Efforts to screen for SCD have been highly prioritized in these areas despite limited resources. However, follow up after diagnosis remains a challenge. Counterintuitively, many of those diagnosed with SCD are lost to follow up after screening while others lack access to treatment that would otherwise prevent them from developing adverse health effects of SCD which is the primary reason for screening for the disease. Objectives: To determine the rate of enrollment of children with sickle cell disease into comprehensive sickle cell clinic and initiation of sickle cell treatment after screening positive for SCD. Methodology: This is a cross sectional study. Families of children aged 5 years and below who screened positive for SCD as part of a validation of point of care test between 2017 and 2018 in Homabay County Referral Hospital in Kenya were contacted by phone and an inquiry was made on their health status, clinic visits and treatment for SCD. Five attempts were made at reaching the families within a period of one week. Data were analyzed using frequency tables. Results: Seven hundred children under 5 years were screened for SCD between 2017 and 2018 at Homabay County Referral Hospital and 34 were found to have sickle cell disease by screening and confirmatory testing. The mean age at the time of testing was 24 months (range 4 to 59 months). Mean follow up time was 33 months after diagnosis(range 32-35 months). Twenty-seven participants were reachable on phone and 8 could not be traced. Out of those contacted three had died from possible infectious diseases and one had stopped attending sickle cell clinic for unclear reasons. Twenty-three children were consistent with clinic attendance and were taking folic acid, and proguanil for malaria prophylaxis. Eight had not been started on hydroxyurea because they were asymptomatic for sickle cell. Fifteen patients who had been started on hydroxyurea had already experienced at least 3 or more painful crises, hospitalizations, febrile illness, or more than 1 blood transfusions within a year. These criteria are used to initiate hydroxyurea because of limited supply. In a setting where typically more than 50% of children screened for SCD are lost to follow up, 77% of the children were traceable and of those alive 96% were enrolled to comprehensive sickle cell clinic. Preliminary results from screening with point of care test permitted intensive education of families with a child highly likely to have SCD. This likely contributed to the high proportion of children attending SCD clinic. Relocation of families and unreliable phone contacts may have contributed to cases of lost to follow up. Conclusion: While screening for SCD is crucial for timely diagnosis and prevention of life-threatening complication of SCD, establishing consistent follow-up of patients is challenging. Timely screening results and education based on these results is an effective strategy to increase SCD clinic attendance, treatment adherence, and improve outcomes in children with SCD. Disclosures Strouse: Takeda: Consultancy.

Background Over the last five decades, advancements in management of sickle cell disease (SCD) have led to more individuals living beyond the median life expectancy, which has historically been 14 years based on autopsy data in 1973, to approximately 40 to 45 years in population-based studies and 61 years in recent cohorts from comprehensive programs. Despite the increasing life expectancy for people with SCD, there is a paucity of literature on the unique experiences of older adults with SCD (age > 50). This limits providers' understanding of how to address the unique needs of older adult patients with SCD as they age. Thus, the purpose of this study was to describe experiences with aging for older adults with SCD. Methods We recruited 19 older adults with SCD (age > 50) from a single academic comprehensive SCD center in the Southeastern United States. We conducted semi-structured qualitative interviews by phone and in person. Participants were asked open-ended questions about their experiences living with SCD, aging, and surviving beyond the SCD life expectancy. Audio-recorded interviews were transcribed verbatim. The transcripts were analyzed using conventional content analysis. Results The mean age of participants was 58 years (range 50-71) and 47% (n=9) were female. The majority of participants were married or had a domestic partner (58%, n=11) and 47% (n=9) were working. Most participants had HbSS genotype (53%, n=10), 37% (n=7) had HbSC, and 11% (n=2) had HbSβ+-thalassemia. Most people reported current use of hydroxyurea (58%, n=11) and their most common chronic complications were avascular necrosis (79%, n=15), retinopathy (58%, n=11), and chronic kidney disease (47%, n=9). Participants described their experiences aging and living beyond the life expectancy for SCD, encompassed in three themes (Figure 1): Theme 1 was "challenges with SCD across the lifespan," which focused on obstacles participates described from youth to adulthood, including experiencing pain and complications of SCD, but not being diagnosed with SCD until later in their childhood or until as late as mid-life. They described multiple obstacles as an older adult with SCD, including challenges maintaining employment, limitations in physical and social activities, and additional health problems such as kidney disease, increased fatigue, and pulmonary complications. They also reported perceiving healthcare providers were not knowledgeable enough about SCD to properly care for them. Theme 2 was "knowledge and self-management of SCD improves with age," where participants described differences between being younger vs. older with SCD, including sharing lessons they learned over time about managing SCD, which made them feel more knowledgeable about how to care for themselves in their older age. They described strategies that helped prevent and manage pain crises, such as preparing for weather extremes, learning personal triggers for sickle cell crises, knowing when to rest and when to keep moving, hydration, and being proactive with their SCD care. Theme 3 was "surpassing life expectancy," where participants discussed how their expectations for their life expectancy changed throughout their lives, and how their life expectancy was influenced by their family members, healthcare providers, and personal experiences and beliefs. Participants described being told by doctors at a young age that they would not live past age 18; however, when they made it to adulthood, some participants conveyed how they stopped allowing their prognosis to influence their thinking. Instead, they chose to trust in God that they would live long. Most participants said that their faith in God and healthy lifestyle choices were the main reasons why they surpassed the life expectancy for SCD. Conclusion These findings described the experiences conveyed by older adults with SCD about living beyond their expected lifespan. These data provide direction for providers to address areas of care that are most important to this older population and inform development of interventions to increase the knowledge of providers about SCD and health self-efficacy. The information these participants shared will also provide guidance for younger adults with SCD as they navigate the aging process and implement strategies that can support successful aging with SCD. Figure 1 Figure 1. Disclosures Strouse: Takeda: Consultancy.

Introduction: Pregnancies of women with sickle cell disease (SCD) have increased risk of morbidity and mortality, with potential additional complications due to uncertain teratogenicity of hydroxyurea and the newer medications. Unintended pregnancy is common among adolescents and young adults (AYA). We aimed to assess the beliefs, practices and barriers of U.S. pediatric hematology providers related to contraception for female AYA with SCD, as little is known about this topic. Methods: We developed a 25-question, web-based survey guided by the Health Belief Model to assess pediatric SCD providers' contraceptive perspectives and practices. Most questions were adapted from published surveys assessing provider views and practices on contraception for general AYA care or patients with other chronic health conditions. The survey was distributed from December 2020-April 2021 to licensed U.S. prescribers who provided care to female SCD AYAs ages 12-21 years within the prior two years. The anonymous survey was distributed by two methods: (1) a list of 526 pediatric SCD and/or general hematology providers from the HRSA SCD Treatment Demonstration Program Regional Collaborative, cross-referenced for reminder emails to 126 providers using a list from the HRSA Regional Genetics Collaborative (https://www.hrsa.gov); (2) directors from all 74 U.S. ACGME-accredited Pediatric Hematology-Oncology fellowship programs, asking then to forward the survey to their SCD providers. Surveys with >50% completion were analyzed using descriptive statistics and chi square analyses. Results: Of 177 respondents, 160 surveys met inclusion criteria and were analyzed: 73 (45.6%) contacted by emails and 87 (54.4%) contacted via the fellowship directors (Table 1). Respondents recruited via fellowship program directors were more frequently NP/PAs (total of 30 (18.7%)), of younger age (total 103 (64.4%) and had fewer years in practice compared to those contacted directly. The majority of providers reported counseling (76.9%) and/or referring patients for contraception (90.9%), but not prescribing (41.8%). Practices regarding contraception differed by provider characteristics (Table 2). Trainees vs. established providers less frequently reported counseling about contraception (54.1% vs. 84.6%, p30% respondents) were insufficiencies in time, patient/parent willingness, formal training, knowledge/ability and/or professional guidelines. Concerns about side effects was a barrier to prescribing (34.2%), while lack of access to providers with contraceptive expertise was the most common barrier to patient referral (34.9%). Multivariate analyses are ongoing. Conclusions: To our knowledge, this is the first national report of pediatric hematology providers' beliefs and practices regarding contraception for female AYA with SCD. While providers generally felt responsible for offering counseling and referral but not prescribing, practices varied based on certain provider characteristics, beliefs and perceived barriers. Clinical guidelines, improved provider education and training, and patient/parent decision Figure 1 Figure 1. Disclosures Smith-Whitley: Global Blood Therapeutics: Current Employment. Strouse: Takeda: Consultancy.

A clinician diagnosis of asthma is associated with increased morbidity and mortality in people with sickle cell disease (SCD). We hypothesized that a screening program would help identify children with asthma needing referral to pulmonary clinic. We conducted a single-center project to screen patients with SCD for asthma using a previously validated questionnaire (Breathmobile) and for pulmonary function abnormalities with portable spirometry. Participants with a positive questionnaire and/or abnormal spirometry were referred to pediatric pulmonary clinic. We evaluated clinical associations with abnormal spirometry and questionnaire responses. Of the 157 participants, 58 (37%) had a positive asthma screening questionnaire. Interpretable spirometry was available for 105 (83% of those eligible) and of these, 35 (34%) had abnormal results. The asthma questionnaire was 87.5% sensitive [95% confidence interval (CI) 74.8–95.3] and 85.3% specific (95% CI 77.3–91.4) to detect a clinician diagnosis of asthma. Participants with positive questionnaires were older (mean age 12.2 vs. 9.9 years, P = 0.012). Spirometry identified 16 additional participants who had normal asthma questionnaires. Seventy-four participants (47%) were referred to pediatric pulmonary clinic and 25 (34%) of these participants scheduled clinic appointments; however, only 13 (52%) were evaluated in pulmonary clinic. Clinic-based asthma screening and spirometry frequently identified individuals with asthma and pulmonary function abnormalities. Only 22% of those referred were eventually seen in pulmonary clinic. The impact of improved screening and treatment on the pulmonary morbidity in SCD needs to be defined and is an area for future investigation. In addition, case management or multidisciplinary clinics may enhance future screening programs.

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO2 to maintain constant CMRO2. Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%–33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%–22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

BACKGROUND Factor (F)XIII deficiency is a rare inherited bleeding disorder, but can also be acquired due to the development of inhibitors. CASE REPORT A 17-year-old female with systemic lupus erythematosus and end-stage kidney disease secondary to Class IV lupus nephritis developed spontaneous subcutaneous and muscular hematomas and delayed major bleeding after invasive procedures. She had abnormal kaolin thromboelastography (kTEG; decreased maximal amplitude, representative of clot strength) initially attributed to thrombocytopenia and uremic platelet dysfunction, but her FXIII activity was undetectable, and a high-titer antibody against FXIII was identified. She had improvement in clinical bleeding and in kaolin thromboelastogram result and transient improvement in FXIII activity after each dose of plasma-derived FXIII concentrate (Corifact) or cryoprecipitate. Her inhibitor titers gradually improved with multiple immunosuppressive therapies and plasma exchange. While her FXIII activity level remained mildly decreased, she has not had additional significant bleeding. CONCLUSION Treatment with either plasma-derived FXIII or cryoprecipitate is an effective treatment to normalize the kTEG variables and clinical bleeding diatheses associated with acquired FXIII inhibitors. Higher doses may be needed in patients with high-titer inhibitor.

Background Life expectancy for individuals with sickle cell disease (SCD) has improved significantly in the last 50 years, creating a new population of older adults with SCD; however, life expectancy of adults with SCD is still up to 30 years shorter than African Americans in the general population and much lower than whites. SCD complications cause significant morbidity, requiring patients to make complex decisions about end of life care. Yet, there is a paucity of literature on SCD advance care planning (ACP), to guide providers on how to address ACP in this population. Thus, the purpose of this study was to assess barriers and facilitators to ACP for older adults with SCD. Methods We recruited 19 older adults with SCD (age > 50) from a comprehensive SCD center in the Southeastern United States. We conducted semi-structured interviews by phone or in person. Interview questions addressed aging with SCD, living beyond SCD life expectancy, experience with health care, experience with end of life care, comfort discussing death and end of life care, presence and nature of prior ACP discussions, and preferences for future ACP discussions. Audio-recorded interviews were transcribed verbatim. The data were analyzed using conventional content analysis. Results The mean age of participants was 57 years (range 50-71) and 47% (n = 9) were female. Most participants were diagnosed with SCD several years after birth and were told that they were not expected to live past age 18. Four of 19 participants had written advanced directives. Most participants were comfortable and willing to discuss ACP and thought that SCD ACP discussions should ideally start in early adulthood. Barriers to ACP included lack of communication, inappropriate contexts for ACP discussions, lack of trust, difficulty navigating ACP documents, and spirituality (Figure 1). Lack of communication included limited to no communication from trusted healthcare providers about ACP preferences. Inappropriate contexts for ACP discussions included being approached at difficult times by unfamiliar providers, such as being asked to complete advance directives while sick in the hospital by a provider who did not know the patient well. Trust was a barrier, as several participants were concerned that being asked about ACP while sick meant providers were giving up on them; others were unsure if they could trust providers or family members to carry out their end of life wishes as written. They reported difficulty navigating ACP documents and several participants incorrectly assumed a lawyer was required to finalize ACP documents. Finally, spirituality was a barrier as some participants reported that end of life planning was inconsistent with their religious beliefs. Facilitators of ACP included discussion at the right time, provider familiarity and knowledge, presence of family, and assistance in completing ACP documents. Participants expressed a desire to have an opportunity to openly communicate their end of life wishes with their provider when they were not sick in the hospital. They preferred discussing ACP with a provider whom they had a good relationship with, was familiar with their history, and they perceived was knowledgeable about SCD. Participants identified their SCD provider, PCP, or pulmonologist as suitable providers to talk to about ACP. Most preferred their family to be present during the ACP discussion. Those that had already completed advance directives at the time of the study received assistance from someone outside the health system to do so, such as help from their church, a lawyer, or their family. Conclusion Older adults with SCD expressed a desire for communication about ACP from trusted providers who are knowledgeable about SCD and want to have ACP conversations when they are feeling well. In addition, having the patient's family present and giving them assistance may increase the patient's comfort in completing their advance directives. The lack of communication from trusted providers or communication from unfamiliar providers about ACP during hospitalizations for acute complications are major barriers to creating advance directives for older adults with SCD. Future research is needed to obtain providers' perspectives on barriers to initiating conversations about ACP with adults with SCD. We will use these results to inform development of patient-centered and culturally-sensitive interventions to improve ACP in adults with SCD. Disclosures Strouse: Takeda: Research Funding.

Background Nearly 95% of individuals with sickle cell disease (SCD) live to become adults (age ≥ 18 years). As individuals with SCD age, they acquire both SCD and age-related complications leading to functional decline. There is a growing need for stragies to improve their function and quality of life.The purpose of this study was to assess the feasibility and acceptability of a sickle cell disease functional assessment (SCD-FA) in both younger and older adults with SCD. Methods We enrolled 20 younger adults (age 18-49 years) and 20 older adults (age ≥ 50 years) in a prospective cohort study. We included measures previously validated in functional geriatric assessment for oncology patients enriched with additional physical and cognitive functional measures. We monitored physical activity for 7 days using the Actigraph wT3X-BT. The primary endpoint was the proportion of subjects who complete the assessment. Secondary endpoints were duration of the SCD-FA, proportion who completed activity monitoring and biospecimen collection, and acceptability. Results Eighty percent (44/55) of adults approached for the study consented, and 91% (40) of consented participants completed the SCD-FA. The median duration of the assessment was 89 minutes (IQR 80-98 minutes), and there were no adverse events. A comparison of characteristics of younger and older participants is shown in Table 1. The mean usual gait speed (GS) was similar between younger and older adults, 1.10 m/s and 1.14m/s, respectively (p = 0.57). Both males and females in each age group had a GS similar to non-SCD adults over the age of 80 (Table 2). There was no difference detected in GS between participants with and without avascular necrosis (AVN) (1.12 m/s vs 1.13 m/s, respectively, p = 0.89) nor between severe SCD genotypes (HbSS and HbSß0) and less severe genotypes (HbSC and HbSß+) (1.08 m/s vs 1.18 m/s, respectively, p =0.13). There was no correlation between hemoglobin and GS (ρ = 0.22, p = 0.17). Young and old exhibited similar performance on the Timed Up and Go (TUG) with a mean time of 9.2 seconds for younger adults and 10.1 seconds for older adults (p = 0.14). Younger adults walked farther on the six-minute walk test (6MWT) compared to older adults (546 meters vs 482 meters p = 0.04). There was no difference in 6MWT between participants with and without AVN (499 meters vs 537 meters, p = 0.22), and no correlation between hemoglobin and distance on 6MWT (rs = 0.20, p = 0.21). Younger adults had a better performance on the 30-second chair stand test (30sCST) with a mean of 14 (range 4-22) vs 11 (range 3-16) in older adults, p = 0.02. There was no difference in 30sCST in people with or without avascular necrosis (12 vs 14, respectively, p = 0.24). Nearly all participants (95%) completed activity monitoring (18 younger adults and 18 older adults). Younger adults wore the monitors for a mean of 8 days (range 4-12) and older adults wore it for a mean of 7 days (range 4-10). The median step count for younger adults was 9253 steps/day (IQR 6449-10546) and the median step count for older adults was 6839 steps/day (IQR 6304-8144) (p = 0.44). The majority of both younger and older adult's activity was sedentary (42-44% of weartime) or light (47-48% of weartime). On the acceptability survey, 95% (38/40) reported that the length of the assessment was appropriate and particiants even had suggestions for additional questions to add. One participant found a question upsetting, about a history of drug use. 5% (2/40) reported portions as difficult to understand. When asked about feedback on removing items from the SCD-FA, 10% (4/40) recommended removing the Montreal Cognitive Assessment due to difficulty. Conclusions The SCD-FA was feasible, acceptable, and safe in both older and younger adults with SCD. There was no difference in GS in older and younger adults with SCD. Similar to older adults with SCD, younger adults had a mean GS similar to non-SCD adults over the age of 80. Younger adults did have significantly a better performance on the 6MWT and 30sCST compared to older adults, which may suggest better aerobic endurance and lower body strength. GS is one of the most powerful predictors of morbidity and mortality in non-SCD geriatric populations but its role in SCD awaits larger longitudinal samples. In future studies we will explore the role of GS and other components of the SCD-FA in predicting patient-important outcomes and mortality. Disclosures Strouse: Takeda: Research Funding.

The transition period from pediatric care to adult care for patients with sickle cell disease (SCD) is associated with increased mortality and morbidity. Identification of risk factors for unsuccessful transition may aid in developing strategies to improve the transition process and health outcomes in this population. We examined factors associated with unsuccessful transition from pediatric to adult care for patients with SCD at the Johns Hopkins Hospital. We found that public insurance and increased hospitalization rates were associated with poor transition to adult care. The findings provide possible areas of intervention.

PURPOSE: To evaluate different T(2)-oxygenation calibrations for estimating venous oxygenation in people with sickle cell anemia (SCA). METHODS: Blood T(2) values were measured at 3T in the internal jugular veins of 12 healthy volunteers and 11 SCA participants with no history of stroke, recent transfusion, or renal impairment. T(2)-oxygenation relationships of both sickled and normal blood samples were calibrated individually and compared with values generated from published models. After converting venous T(2) values to venous oxygenation, whole-brain oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) were calculated. RESULTS: Sickle blood samples’ oxygenation values (Y) calculated from our individual calibrations agreed well with measurements using a blood analyzer, while previous T(2) calibrations based on normal blood samples showed 13–19% underestimation. Meanwhile, Y values calculated from previous grouped T(2) calibration for sickle blood agreed well with experimental measurement on averaged values, but showed up to 20% variation for several individual samples. Using individual T(2) calibrations, the whole-brain OEF and CMRO(2) of SCA participants were 0.38+/−0.08 and 172+/−42μmol/min/100g, respectively, which were comparable to those values measured on normal volunteers. CONCLUSION: Our results confirm that sickle blood T(2) values not only depend on Hct and Y, but also on other hematological factors. The individual T(2) calibrations minimized the effect of heterogeneity of sickle blood between different SCA populations and improved the accuracy of T(2)-based oximetry. The measured OEF and CMRO(2) of this group of SCA participants were found to not differ significantly from those of healthy people.

Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6-4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA.

Objectives Transcranial Doppler ultrasound (TCD) effectively identifies children with sickle cell anemia (SCA) who are at increased risk of stroke. We evaluated a low-cost quality improvement (QI) intervention to increase the proportion of children screened by TCD. Methods We measured the proportion of children with SCA receiving appropriate TCD screening for increased cerebral blood velocity, a marker of stroke risk, for time periods before (April 1, 2009-July 1, 2010) and after (October 1, 2010-January 1, 2012) the implementation of a QI program. We sent eligible families personalized reminder letters, information on screening, and a refrigerator magnet imprinted with the recommended date of TCD screening. Results Only 54% (60/112) of children (median age 8 years, range 2.2-16.7 years) had a TCD in the baseline period compared with 79% (87/110; P = 0.0001) after implementation of the QI initiative. The odds of appropriate TCD screening decreased with older age in the baseline period (odds ratio 0.86, 95% confidence interval 0.78-0.94/year; P = 0.001), but not after implementation. Neither predicted travel time by car (median 20 minutes, range 2-164) nor distance traveled (median 9.7 mi, range 0.4-132) was significantly associated with appropriate TCD screening before or after QI implementation. The number needed to treat was four. Conclusions We demonstrated the feasibility and effectiveness of a low-cost QI intervention to increase TCD screening. This approach was more successful than other related intervention models and is easily implemented by smaller sickle cell programs without full-time personnel.

Objectives Neurocognitive dysfunction is an important complication of sickle cell disease (SCD), but little is published on the utility of screening tests for cognitive impairment in people with the disease. The purpose of this study was to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool and identify predictors of MoCA performance in adults with sickle cell disease. Methods We conducted a retrospective, cross-sectional study of the first 100 adult patients with SCD who completed the MoCA as part of routine clinical care at the Johns Hopkins Sickle Cell Center for Adults. We abstracted demographic, laboratory, and clinical data from each participant's electronic medical record up to the date that the MoCA was administered. The factorial validity of each MoCA domain was analyzed using standard psychometric statistics. We evaluated the abstracted data for associations with the composite MoCA score and looked for independent predictors of performance using multivariable regressions. Results Components of the MoCA performed well in psychometric analyses and identified deficits in executive function that were described in other studies. Forty-six percent of participants fell below the cutoff for mild cognitive impairment. Increased education was an independent predictor of increased MoCA score (3.1, 95% confidence interval [CI] 1.5-4.7), whereas cerebrovascular accidents and chronic kidney disease were independent predictors of decreased score (-3.3, 95% CI -5.7 to -0.97 and -3.2, 95% CI -6.2 to -0.11, respectively). When analysis was restricted to patients with SCA, increased education (3.7, 95% CI 2.2-5.2) and a history of hydroxyurea therapy (2.0, 95% CI -0.022 to 4.0) were independent predictors of a higher score, whereas chronic kidney disease (-3.3, 95% CI -6.4 to -0.24) and increased aspartate transaminase (-0.045, 95% CI -0.089 to -0.0010) were independent predictors of a decreased score. Conclusions The MoCA showed promise by identifying important cognitive deficits and associations with chronic complications and therapy.

Purpose To develop a fast protocol for measuring T1 values in the internal carotid artery (ICA), to validate this technique with in vitro measurements, and to evaluate its reproducibility. Methods A modified Look–Locker sequence was optimized to enable rapid determination of T1 in the ICA at 3T. T1 values from the ICA were compared with in vitro measurements on individually sampled venous blood oxygenated to arterial levels. A test–retest reproducibility study was also conducted. Results The group-averaged arterial blood T1 value was 1908 ± 77 ms for six women (hematocrit = 0.39 ± 0.03) and 1785 ± 55 ms for seven men (hematocrit = 0.45 ± 0.02), which is 100–200 ms longer than the widely adopted value obtained from bovine blood experiments. The arterial T1 value per subject correlated significantly with individual hematocrit values. The intrasession and intersession coefficients of variation were 1.1% and 2.1%, respectively, indicating good precision and reproducibility of our method. Reasonable agreement was observed between the in vivo and in vitro results with a correlation coefficient of 0.78. Conclusion The proposed method can provide fast arterial T1 measurement on individual subjects. When not performing such a subject-specific measurement, we recommend the use of 1908 ms and 1785 ms for healthy women and men, respectively, or 1841 ms for adults in general. Magn Reson Med 77:2296–2302, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Community health workers are increasingly recognized as useful for improving health care and health outcomes for a variety of chronic conditions. Community health workers can provide social support, navigation of health systems and resources, and lay counseling. Social and cultural alignment of community health workers with the population they serve is an important aspect of community health worker intervention. Although community health worker interventions have been shown to improve patient-centered outcomes in underserved communities, these interventions have not been evaluated with sickle cell disease. Evidence from other disease areas suggests that community health worker intervention also would be effective for these patients. Sickle cell disease is complex, with a range of barriers to multifaceted care needs at the individual, family/friend, clinical organization, and community levels. Care delivery is complicated by disparities in health care: access, delivery, services, and cultural mismatches between providers and families. Current practices inadequately address or provide incomplete control of symptoms, especially pain, resulting in decreased quality of life and high medical expense. The authors propose that care and care outcomes for people with sickle cell disease could be improved through community health worker case management, social support, and health system navigation. This report outlines implementation strategies in current use to test community health workers for sickle cell disease management in a variety of settings. National medical and advocacy efforts to develop the community health workforce for sickle cell disease management may enhance the progress and development of “best practices” for this area of community-based care.

Preventive services can reduce the morbidity of sickle cell disease (SCD) in children but are delivered unreliably. We conducted a retrospective cohort study of children ages 2–5 years with SCD, evaluating each child for 14 months and expecting that he/she should receive ≥75% of days covered by antibiotic prophylaxis, ≥1 influenza immunization, and ≥1 transcranial Doppler ultrasound (TCD). We used logistic regression to quantify the relationship between ambulatory generalist and hematologist visits and preventive services delivery. Of 266 children meeting inclusion criteria, 30% consistently filled prophylactic antibiotic prescriptions. Having ≥2 generalist, non-well child care visits or ≥2 hematologist visits was associated with more reliable antibiotic prophylaxis. Forty-one percent of children received ≥1 influenza immunizations. Children with ≥2 hematologist visits were most likely to be immunized (62% versus 35% among children without a hematologist visit). Only 25% of children received ≥1 TCD. Children most likely to receive a TCD (42%) were those with ≥2 hematologist visits. One in twenty children received all three preventive services. Preventive services delivery to young children with SCD was inconsistent but associated with multiple visits to ambulatory providers. Better connecting children with SCD to hematologists and strengthening preventive care delivery by generalists are both essential.

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.

Sickle cell disease (SCD) and cystic fibrosis (CF) are severe autosomal recessive disorders associated with intermittent disease exacerbations that require hospitalizations, progressive chronic organ injury, and substantial premature mortality. Research funding is a limited resource and may contribute to health care disparities, especially for rare diseases that disproportionally affect economically disadvantaged groups.To compare disease-specific funding between SCD and CF and the association between funding and research productivity.This cross-sectional study examined federal and foundation funding, publications indexed in PubMed, clinical trials registered in ClinicalTrials.gov, and new drug approvals from January 1, 2008, to December 31, 2018, in an estimated US population of approximately 90 000 individuals with SCD and approximately 30 000 individuals with CF.Federal and foundation funding, publications indexed in PubMed, clinical trial registrations, and new drug approvals.From 2008 through 2018, federal funding was greater per person with CF compared with SCD (mean [SD], $2807 [$175] vs $812 [$147]; P .001). Foundation expenditures were greater for CF than for SCD (mean [SD], $7690 [$3974] vs $102 [$13.7]; P .001). Significantly more research articles (mean [SD], 1594 [225] vs 926 [157]; P .001) and US Food and Drug Administration drug approvals (4 vs 1) were found for CF compared with SCD, but the total number of clinical trials was similar (mean [SD], 27.3 [6.9] vs 23.8 [6.3]; P = .22).The findings show that disparities in funding between SCD and CF may be associated with decreased research productivity and novel drug development for SCD. Increased federal and foundation funding is needed for SCD and other diseases that disproportionately affect economically disadvantaged groups to address health care disparities.

Tobacco smoke exposure has been associated with more frequent hospitalizations in children with sickle cell disease (SCD), but previous studies have not quantified the exposure by objective methods. We enrolled 50 children and young adults with SCD in a retrospective and prospective cohort study and quantified tobacco smoke exposure by objective (salivary cotinine) and survey measures. We used a multivariable negative binomial regression model to evaluate the association between salivary cotinine and hospital admissions. Forty-five percent (22/49) of participants had significant elevation of salivary cotinine (≥ 0.5 ng/ml). The incidence risk ratio (IRR) for hospital admission for those with elevated cotinine was 3.7 (95% CI 1.8-8). Those exposed to secondhand smoke but not primary smokers (cotinine between 0.5 and 10 ng/ml) had a similarly increased risk of hospitalization [IRR 4.3 (95% CI 1.8-10)]. We show that an objective measure of tobacco smoke exposure, salivary cotinine, is strongly associated with the rate of hospital admissions in children and young adults with SCD. This association underscores the importance of screening for tobacco smoke exposure in people with SCD. Further investigation is warranted to determine the mechanisms of and to evaluate interventions to decrease tobacco smoke exposure.

Patients with low educational attainment may be at increased risk for unplanned health care utilization. This study aimed to determine what factors are related to emergency department (ED) visits in hopes of guiding treatments and early interventions. At two medical centers in the Mid-Atlantic United States, 258 adults with sickle cell disease aged 19–70 years participated in a retrospective study where we examined whether education level is independently associated with ED visits after accounting for other socioeconomic status (SES) variables, such as pain and disease severity and psychosocial functioning. The data showed that patients without a high school education visited the ED three times as frequently as patients with post secondary education. Controlling for poverty and employment status decreased the effect of education on ED visits by 33.24 %. Further controlling for disease severity and/or psychosocial functioning could not account for the remaining association between education and ED visits, suggesting that education is independently associated with potentially avoidable emergency care. Early interventions addressing disparities in academic performance, especially for those children most at risk, may lead to improved long-term health outcomes in this population.