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Racism is an established health determinant across the world. In this 3-part series, we argue that a disregard of how racism manifests in pain research practices perpetuates pain inequities and slows the progression of the field. Our goal in part-1 is to provide a historical and theoretical background of racism as a foundation for understanding how an antiracism pain research framework - which focuses on the impact of racism, rather than “race,” on pain outcomes - can be incorporated across the continuum of pain research. We also describe cultural humility as a lifelong self-awareness process critical to ending generalizations and successfully applying antiracism research practices through the pain research continuum. In part-2 of the series, we describe research designs that perpetuate racism and provide reframes. Finally, in part-3, we emphasize the implications of an antiracism framework for research dissemination, community-engagement practices and diversity in research teams. Through this series, we invite the pain research community to share our commitment to the active process of antiracism, which involves both self-examination and re-evaluation of research practices shifting our collective work towards eliminating racialized injustices in our approach to pain research. Perspective: We call on the pain community to dismantle racism in our research practices. As the first paper of the 3-part series, we introduce dimensions of racism and its effect on pain inequities. We also describe the imperative role of cultural humility in adopting antiracism pain research practices.

The coronavirus pandemic identified a clinical need for pediatric tele-neuropsychology (TeleNP) assessment. However, due to limited research, clinicians have had little information to develop, adapt, or select reliable pediatric assessments for TeleNP. This preliminary systematic review aimed to examine the feasibility of pediatric TeleNP assessment alongside (1) patient/family acceptability, (2) reliability, and (3) the quality of the literature. Between May 2021 and November 2022, manual searches of PubMed, PsycINFO, and Google Scholar were conducted using terms related to “pediatric” and “tele-neuropsychology.” After extracting relevant papers with samples aged 0–22 years, predefined exclusion criteria were applied. Quality assessment was completed using the AXIS appraisal tool (91% rater-agreement). Twenty-one studies were included in the review, with reported qualitative and quantitative data on the feasibility, reliability, and acceptability extracted. Across included studies, TeleNP was completed via telephone/video conference with participants either at home, in a local setting accompanied by an assistant, or in a different room but in the same building as the assessor. Pediatric TeleNP was generally reported to be feasible (e.g., minimal behavioral differences) and acceptable (e.g., positive feedback). Nineteen studies conducted some statistical analyses to assess reliability. Most observed no significant difference between in-person and TeleNP for most cognitive domains (i.e., IQ), with a minority finding variable reliability for some tests (e.g., attention, speech, visuo-spatial). Limited reporting of sex-assigned birth, racialized identity, and ethnicity reduced the quality and generalizability of the literature. To aid clinical interpretations, studies should assess underexamined cognitive domains (e.g., processing speed) with larger, more inclusive samples.

Objective: Individuals with sickle cell disease (SCD) are at increased risk for complications from their disease during their adolescent and young adult (AYA) years. The risk of morbidity in AYAs with SCD can be decreased with improved self-management. Existing self-management interventions typically focus on one aspect of self-management (e.g., adherence) and do not address factors that activate patients (knowledge, motivation, self-efficacy, and social support) to self-manage. Sickle Cell Thrive (SCThrive) is a mixed in-person/online, technology-enhanced (use of a mobile app), group self-management intervention that targets patient activation. To determine the most clinically significant intervention components, a qualitative study was conducted. Method: Participants were 19 AYAs (Mage = 17.05) with SCD who participated in individual semistructured phone interviews after completing SCThrive. Interview content was coded using a grounded-theory approach to generate themes related to SCThrive’s feasibility, acceptability, and motivation for and impact on self-management. Results: SCThrive was reported to be highly feasible due to the mixed in-person/online format and acceptable because they learned skills to manage SCD in a group of AYAs with SCD. Action planning and pain/mood tracking appeared to be key factors in motivating AYAs for self-management. Participants reported continuing to use self-management skills post-SCThrive (self-efficacy) including applying them to other domains of their lives (e.g., educational/vocational). Conclusions: Study results provide data that can be leveraged to enhance the feasibility, acceptability, and impact of SCThrive and other self-management interventions. Findings can also inform clinical and mobile health interventions to increase self-management in this population. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO 2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO 2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO 2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO 2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA.

Although hydroxyurea (HU) is an effective treatment for sickle cell anemia, uptake remains low. Shared decision making (SDM) is a recommended strategy for HU initiation to elicit family preferences; however, clinicians lack SDM training. We implemented an immersive virtual reality (VR) curriculum at eight pediatric institutions to train clinicians on SDM that included counseling virtual patients. Clinicians’ self-reported confidence significantly improved following the VR simulations on all communication skills assessed, including asking open-ended questions, eliciting specific concerns, and confirming understanding (ps ≤ 0.01 for all). VR may be an effective method for educating clinicians to engage in SDM for HU.

The educational services available for fully included middle schoolers with autism spectrum disorder (ASD) in the general education setting in the United States are not well known. Even less is known about how the executive functioning (EF) deficits of such youth are addressed in the classroom. The current study sought to identify the challenges, including EF, that middle schoolers with ASD face, determine the services that they receive on their Individualized Education Program (IEP), and also explore specific strategies used to build EF skills at school. A convenience data sample was obtained from focus groups with educational personnel ( n = 15), and qualitative analyses of IEPs were conducted in middle schoolers with ASD with EF deficits ( n = 23). Results confirmed that social communication and EF challenges are common. Multiple services and accommodations were identified, although EF challenges were rarely targeted on IEPs. Factors that may facilitate the success of EF strategies in the classroom are discussed.

OBJECTIVES: Individuals with sickle cell disease (SCD) experience significant health problems that may result in unpredictable pain episodes and frequent healthcare utilization. Disparities in clinical care may contribute to health-related stigma and racial bias for this majority African-American/Black population. There is less known about the influence of health-related stigma and racial bias on the health-related quality of life (HRQOL) of children with SCD. In the present study, we assessed these relationships and identified differences across demographic factors (i.e., age, gender). DESIGN: Data was collected from African American children with SCD aged 8 – 16 years (57% male, 63% HbSS). Children completed the Childhood Stigma Scale (adapted for SCD), the Child Perceptions of Racism in Children and Youth scale, and the Pediatric Quality of Life Inventory Sickle Cell Disease Module. Caregivers provided demographic information. RESULTS: In the first regression model, health-related stigma (p = .007) predicted HRQOL, but neither age nor gender were significant predictors. In the second regression model, age (p = .03) predicted HRQOL, but neither gender nor racial bias were significant predictors. Of interest, there was a significant interaction between age, gender, and racial bias (p = .02). Specifically, older girls who reported high levels of perceived racial bias had poorer HRQOL. CONCLUSIONS: Our study highlights the need for increased awareness about the effects of health-related stigma and racial bias on HRQOL for children with SCD, particularly for older girls who endorse racial bias. Our findings will guide future stigma and bias reduction interventions that may meet the needs of older girls with SCD.

This third paper in the “Confronting Racism in All Forms of Pain Research” series discusses adopting an antiracism framework across all pain research disciplines and highlights the significant benefits of doing so. We build upon the previous call to action and the proposed reframing of study designs articulated in the other papers in the series and seek to confront and eradicate racism through a shared commitment to change current research practices. Specifically, we emphasize the systematic disadvantage created by racialization (i.e., the Eurocentric social and political process of ascribing racialized identities to a relationship, social practice, or group) and discuss how engaging communities in partnership can increase the participation of racialized groups in research studies and enrich the knowledge gained. Alongside this critical work, we indicate why diversifying the research environment (i.e., research teams, labs, departments, and culture) enriches our scientific discovery and promotes recruitment and retention of participants from racialized groups. Finally, we recommend changes in reporting and dissemination practices so that we do not stigmatize or reproduce oppressive forms of power for racialized groups. Although this shift may be challenging in some cases, the increase in equity, generalizability, and credibility of the data produced will expand our knowledge and reflect the pain experiences of all communities more accurately.Perspective: In this third paper in our series, we advocate for a shared commitment toward an antiracism framework in pain research. We identify community partnerships, diversification of research environments, and changes to our dissemination practices as areas where oppressive forms of power can be reduced.Keywords: antiracism; equity; inclusion; bias; language

BackgroundDevelopmental difficulties in many cognitive domains are common in children with sickle cell anaemia (SCA). Children with stroke are most affected but delayed or atypical cognitive function has been reported in children with SCA and silent infarcts (SCI), vasculopathy, and normal brain MRI. However, very few studies of cognition have been conducted in Africa, a continent with 75% of the SCA burden. We therefore investigated cognitive profiles in Tanzanian children with SCA and examined the impact of age, SCI, vasculopathy, and haemoglobin concentration (Hb).MethodsChildren aged 6–16 years with and without SCA were eligible for this cross-sectional study. Cognitive assessment was performed using Raven’s Matrices, assessing fluid, non-verbal intelligence and subtests from the Wechsler Intelligence Scales for Children (WISC-IV), assessing processing speed (PS), perceptual reasoning (PR), and working memory (WM) as these tests are less culture-bound. Magnetic resonance imaging (MRI) and angiography (MRA) were also completed to assess the presence of SCI and vasculopathy. Hb was collected in both SCA children and their non-SCA siblings.ResultsSeventy-three children with SCA and 71 healthy siblings (Meanages 11.9, SD = 2.8 and 11.1, SD = 2.9 years respectively) were recruited. Compared with healthy siblings, children with SCA had lower PS (Meandiff 7.35 points; p = .002). Older children had higher performance scores on all tests in relation to their ages. Lowest cognitive scores were observed on the PS subtest, where patients with SCI (SCI+) had lowest mean values as compared to children with no SCI (SCI-) and healthy siblings (i.e., SCI+ < SCI- < healthy siblings, p = .028). On post-hoc analysis the difference was between SCI+ and healthy siblings SCI+ < non-SCA siblings (p = .015); there was no difference between SCI+ and SCI- patient groups. PS was significantly lower in SCA patients with no vasculopathy as compared to healthy siblings. The mean difference from healthy siblings was -8.352 and -0.752 points for VASC- and VASC + respectively (p = .004). There was a significant positive effect of Hb on PSI (p = .001) in both patients and controls and a trend level significant positive effect of Hb on PR (p = .050) and WM (p = .051).ConclusionIn this Tanzanian study, cognitive performance was reduced in children with SCA with or without SCI on MRI or vasculopathy. Cognitive performance improved with increasing age. Lower Hb was associated with lower cognitive performance in both patients with SCA and their non-SCA siblings. SCI and vasculopathy do not appear to have an impact on cognitive function.

Background/Aims: Recruitment is often a barrier in clinical trials that include minoritized populations, such as individuals with sickle cell disease. In the United States, the majority of people with sickle cell disease identify as Black or African American. In sickle cell disease, 57% of the United States trials that ended early did so due to low enrollment. Thus, there is a need for interventions that improve trial enrollment in this population. After lower-than-expected recruitment during the first 6 months of the Engaging Parents of Children with Sickle Cell Anemia and their Providers in Shared-Decision-Making for Hydroxyurea trial, a multi-site study for young children with sickle cell disease, we collected data to understand barriers and used the Consolidated Framework for Implementation Research to categorize them and guide the development of targeted strategies. Methods: Study staff used screening logs and coordinator and principal investigator calls to identify recruitment barriers that were then mapped onto Consolidated Framework for Implementation Research constructs. Targeted strategies were implemented during Months 7–13. Recruitment and enrollment data were summarized before (Months 1–6) and during the implementation period (Months 7–13). Results: During the first 13 months, 60 caregivers ( M = 30.65 years; SD = 6.35) enrolled in the trial. Most caregivers primarily self-identified as female ( n = 54, 95%) and African American or Black ( n = 51, 90%). Recruitment barriers mapped onto three Consolidated Framework for Implementation Research constructs: (1) Process barriers (i.e. no identified “site champion” and poor recruitment planning at several sites); (2) Inner setting barriers (i.e. limited communication, low relative study priority at several sites); and (3) Outer setting barriers (i.e. poor patient attendance at clinic appointments). Targeted strategies to improve recruitment included (1) principal investigator site visits and retraining on recruitment procedures to address process barriers; (2) increased frequency of communication through all coordinator, site principal investigator, and individual site calls to address inner setting barriers; and (3) development and implementation of no-show procedures for clinic appointments to address outer setting barriers. After implementation of the recruitment strategies, the number of caregivers identified for pre-screening increased from 54 to 164, and enrollment more than tripled from 14 to 46 caregiver participants. Conclusion: Consolidated Framework for Implementation Research constructs guided the development of targeted strategies that increased enrollment. This reflective process reframes recruitment challenges as the responsibility of the research team rather than characterizing minoritized populations as “difficult” or “hard to reach.” Future trials including patients with sickle cell disease and minoritized populations may benefit from this approach.

Background Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. Objective In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. Methods The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper–Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively. Results By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (Ps Conclusions Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics.

Background Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. Methods The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry. Discussion Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA. Trial registration ClinicalTrials.govNCT04351698. Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020

Adolescents and young adults (AYA) with sickle cell disease (SCD) experience health challenges during the move from pediatric to adult care. Self-management (i.e., prioritizing and completing goals) and self-efficacy (i.e., confidence) are needed to manage a chronic disease effectively, but AYA with SCD often lack the skills. Mobile health (mHealth) technology (e.g., smartphones and tablets) present a way for AYA to monitor and track symptoms, change behaviors, and complete goals. We included a mHealth app into a group intervention (SCThrive) to see if using components of the app more frequently increased self-management and self-efficacy for AYA with SCD aged 13–21 years. We found that logging on to the app more often was related to better mood symptoms and lower pain ratings. AYA who logged onto the app more often reported more self-management skills and self-efficacy. Our findings indicate clinical benefits for those AYA with SCD who engaged with the mobile app., Sickle cell disease (SCD) is associated with significant health challenges that often worsen during adolescence. Living with SCD requires a substantial amount of self-management and mobile health (mHealth) holds considerable promise for assessing and changing behaviors to improve health outcomes. We integrated a mobile app as an adjunct to a group intervention (SCThrive) and hypothesized that more engagement with the mHealth app would increase self-management and self-efficacy for adolescents and young adults (AYA) with SCD. Twenty-six AYA ages 13–21 years (54% female; 46% HbSS genotype; all African-American/Black) received six weekly group sessions (three in-person, three online). Participants were provided with the mobile app (iManage for SCD) to record progress on their self-management goals and log pain and mood symptoms. The Transition Readiness Assessment Questionnaire (TRAQ-5) assessed self-management skills and the Patient Activation Measure (PAM-13) assessed self-efficacy at baseline and post-treatment. Logging on to the app more frequently was associated higher mood ratings (r = .54, CI[.18, .77], p = .006) and lower pain ratings (r = −.48, CI[−.77, −.02], p = .04). Regression analyses demonstrated that after controlling for scores at baseline, the number of logins to the app predicted self-management skills (p = .05, η2 = .17) and possibly self-efficacy (p = .08, η2 = .13). Our study findings indicate that it can be challenging to maintain engagement in mHealth for AYA with SCD, but for those who do engage, there are significant benefits related to self-management, self-efficacy, and managing pain and mood.

This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of “race” or “ethnicity” as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups. Perspective: This is the second paper in a 3-part series on antiracism in pain research. This part identifies common study design factors that risk hindering progress toward pain care equity. We suggest reframes using an antiracism framework for these factors to encourage all pain investigators to collectively make strides toward equity.

Background Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term side effects. Moreover, clinicians do not routinely receive training or tools, especially those that provide medical evidence and consider caregivers’ preferences and values, to facilitate a shared discussion with caregivers. Objective The aim of this study is to understand how best to help parents of young children with sickle cell disease and their clinicians have a shared discussion about hydroxyurea (one that considers medical evidence and parent values and preferences). Methods We designed our study to compare the effectiveness of two methods for disseminating hydroxyurea guidelines to facilitate SDM: a clinician pocket guide (ie, usual care) and a clinician hydroxyurea SDM toolkit (H-SDM toolkit). Our primary outcomes are caregiver reports of decisional uncertainty and knowledge of hydroxyurea. The study also assesses the number of children (aged 0-5 years) who were offered and prescribed hydroxyurea and the resultant health outcomes. Results The Ethics Committee of the Cincinnati Children’s Hospital Medical Center approved this study in November 2017. As of February 2021, we have enrolled 120 caregiver participants. Conclusions The long-term objective of this study is to improve the quality of care for children with SCA. Using multicomponent dissemination methods developed in partnership with key stakeholders and designed to address barriers to high-quality care, caregivers of patients with SCA can make informed and shared decisions about their health. Trial Registration ClinicalTrials.gov NCT03442114; https://clinicaltrials.gov/ct2/show/NCT03442114 International Registered Report Identifier (IRRID) DERR1-10.2196/27650

BACKGROUND Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. OBJECTIVE In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. METHODS The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper–Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively. RESULTS By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (PsPs CONCLUSIONS Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics.

Objectives Sickle cell disease (SCD) is a genetic disorder that affects approximately 100,000 Americans, the majority of whom are African American. SCD-related pain often has deleterious effects on functioning and quality of life. The inherited nature of SCD, SCD-related stigma, and serious physical and functional impact of SCD-related pain create a situation ripe for individuals to appraise their SCD-related pain as unfair or unjust. The aim of this preliminary investigation is to explore the extent to which pediatric patients with SCD appraise their pain as unjust and how these appraisals relate to functioning. Methods Participants were youth with SCD (N = 30, mean age = 11.3, 57% boys) who attended a hematology clinic visit. Patients were invited to complete paper-based questionnaires assessing pain-related injustice appraisals, pain catastrophizing, pain and hurt, functional disability, depression, anxiety, and peer relationships. Results Results of hierarchical regressions indicate that pain-related injustice significantly predicted functional disability, depression, and anxiety after controlling for patient pain and catastrophizing. Conclusions These findings suggest that pain-related injustice appraisals are an important contributor to the pain experience of youth with SCD. Early identification and remediation of pain-related injustice appraisals could have long-term functional benefits for youth with SCD.

BACKGROUND Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term side effects. Moreover, clinicians do not routinely receive training or tools, especially those that provide medical evidence and consider caregivers’ preferences and values, to facilitate a shared discussion with caregivers. OBJECTIVE The aim of this study is to understand how best to help parents of young children with sickle cell disease and their clinicians have a shared discussion about hydroxyurea (one that considers medical evidence and parent values and preferences). METHODS We designed our study to compare the effectiveness of two methods for disseminating hydroxyurea guidelines to facilitate SDM: a clinician pocket guide (ie, usual care) and a clinician hydroxyurea SDM toolkit (H-SDM toolkit). Our primary outcomes are caregiver reports of decisional uncertainty and knowledge of hydroxyurea. The study also assesses the number of children (aged 0-5 years) who were offered and prescribed hydroxyurea and the resultant health outcomes. RESULTS The Ethics Committee of the Cincinnati Children’s Hospital Medical Center approved this study in November 2017. As of February 2021, we have enrolled 120 caregiver participants. CONCLUSIONS The long-term objective of this study is to improve the quality of care for children with SCA. Using multicomponent dissemination methods developed in partnership with key stakeholders and designed to address barriers to high-quality care, caregivers of patients with SCA can make informed and shared decisions about their health. CLINICALTRIAL ClinicalTrials.gov NCT03442114; https://clinicaltrials.gov/ct2/show/NCT03442114 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/27650

Background Sickle cell disease (SCD) is associated with significant medical challenges that often worsen in adolescence when caregivers are beginning to transfer responsibility for disease management. Behavioral activation (BA) is an important precedent to improvements in self-management and ultimately health outcomes; however, few interventions targeting BA have been developed for the SCD population. The goal of the present study was to evaluate a technology-enhanced self-management intervention for adolescents and young adults (AYA) with SCD targeting BA domains (ie, disease knowledge, self-efficacy, motivation, and self-management skills). Design/methods Participants were randomized to one of two study arms. SCThrive participants (N = 26) completed six weekly group sessions, an in-person booster session, and used a companion app (iManage) to record symptoms, progress on goals, and connect with other group members. Each SCHealthEd participant (N = 27) received six weekly phone calls on SCD-related and general health education topics. All AYA completed questionnaires assessing BA at baseline and posttreatment. Results Separate mixed ANOVA analyses to assess for the effects of group (SCThrive/SCHealthEd), time (baseline/posttreatment), and group × time interaction indicated that there was a clinically meaningful improvement (8-point change) in self-efficacy, with a medium effect size, P = .09, η2 = .06, and there was statistically significant improvement in one self-management skill (tracking health), P = .001, d = .71, among SCThrive participants. Conclusions The results support the potential for a self-management intervention to improve self-efficacy in AYA with SCD. Health care providers are encouraged to target BA skills to support self-management of AYA with SCD.

Background: Hydroxyurea (HU) is the primary medication used to prevent the significant medical and neurologic morbidities of pediatric sickle cell disease (SCD; HbSS or HbSB0 thalassemia). Despite the benefits of HU, it remains under-utilized likely due to lack of clinician knowledge/training and negative caregiver perceptions. Thus, we developed the Engage-HU randomized controlled trial (NCT03442114) as a novel approach to address HU utilization barriers. Engage-HU is designed to assess how clinicians can engage caregivers in a shared discussion that considers their values, preferences, and scientific evidence about HU. The COVID-19 pandemic has resulted in significant changes to healthcare delivery for children with SCD, as they are at increased risk of severe illness from COVID-19 infection. Given their risk status, it was recommended that patients with SCD complete telehealth visits when possible. Some families also chose to delay care because they feared their child would get infected at hospitals/healthcare clinics that care for COVID-19 positive patients. Since the lives of all families enrolled in the Engage-HU trial have been affected to some extent, we incorporated measures to capture the impact of the COVID-19 pandemic and the usability of telemedicine implementation and services. Methods: Engage-HU is a randomized control trial comparing two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD. Study outcomes include caregiver confidence in decision-making and perceptions of experiencing shared decision-making as well as HU uptake and child health outcomes. Eligible children are 0 to 5 years, candidates for HU, and their caregiver has not decided about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a unidirectional crossover design. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using the intent-to-treat principle, and all participants will remain in the arm to which they were randomized. A multiple group comparison analysis will be performed to assess significant response variable differences by group randomization. The Engage-HU study aims to recruit 174 caregivers who are considering initiating HU. The trial is being conducted at 9 sites in the United States. Data collection is ongoing, and 160 caregiver-participants have been enrolled to date. Since May 2020, caregiver-participants have completed the COVID-19 Exposure and Family Impact Scales (CEFIS), which contain 2 subscales (exposure to potentially traumatic aspects of the pandemic, impact on families), and the COVID-19 telemedicine use survey during a study visit. Results: Currently, 8 of the 9 sites have collected data from 48 caregivers (93.8% mothers), most of whom (93.8%) identify as African American/Black (see Figure 1). Correlations indicated that older caregivers experienced greater exposure (Mean = 7.0, SD = 4.1, range = 1-19) to potentially traumatic aspects of the pandemic (r = .31, p = .04). Distress related to COVID-19 varied widely across the sample, for both caregivers (Mean = 5.9, SD = 2.9, range = 1-10) and children (Mean = 4.1, SD = 3.4, range = 1-10). Scores on the telemedicine usability survey were generally high, indicating that caregivers are happy with the quality of care delivered via telehealth. However, caregivers (r = .30, p = .09) and children (r = .32, p = .07) experiencing more pandemic-related distress reported less satisfaction with telehealth. Conclusion: Although Engage-HU has resumed research operations, recruitment has not reached pre-pandemic targets, as fewer eligible patients are scheduled for routine care visits at SCD clinics. Our preliminary analyses suggest a significant continued impact of the pandemic on families and general satisfaction with the quality of healthcare delivered via telemedicine. These findings indicate that targeted screenings to identify and intervene for those who demonstrate more COVID-19 pandemic-related distress are needed. Figure 1 Figure 1. Disclosures Quinn: Forma Therapeutics: Consultancy; Aruvant: Research Funding; Novo Nordisk: Consultancy; Emmaus Medical: Research Funding. Yates: Agios Pharmaceuticals: Current Employment. Badawy: Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy; Bluebird Bio Inc: Consultancy. Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; Celgene/BMS: Consultancy, Research Funding; CRISPR Therapeutics: Research Funding; Vertex: Research Funding; Editas: Research Funding; Graphite Bio: Research Funding; Novartis: Research Funding; Agios: Consultancy; Beam: Consultancy; Global Blood Therapeutics: Current equity holder in publicly-traded company. Smith-Whitley: Global Blood Therapeutics: Current Employment. King: National Cancer Institute: Research Funding; National Heart, Lung, and Blood Institute: Research Funding; Health Resources and Services Administration: Research Funding; Global Blood Therapeutics: Research Funding. Meier: CVS Caremark: Consultancy; Forma Therapeutic: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Novartis,: Other: Data Safety Monitoring Board membership; NHLBI: Other: Data Safety Monitoring Board membership; Global Blood Therapeutics: Other: Steering Committee membership, grant funding; CDC,: Other: grant funding; Indiana Department of Health: Other: grant funding . Tubman: Global Blood Therapeutics: Consultancy, Research Funding; Novartis Pharmaceuticals: Honoraria, Research Funding; Forma Pharmaceuticals: Consultancy; Perkin Elmer: Honoraria. Crosby: Forma Therapeutics: Honoraria; PCORI: Research Funding; HRSA: Research Funding; Global Blood Therapeutics Panel: Honoraria; Children's Hospital of Philadelphia: Honoraria; Professional Resource Exchange: Patents & Royalties: $30-$60 every other year; SCDAA: Honoraria; NHLBI: Other: Payment for review of LRP Proposals, Research Funding. OffLabel Disclosure: Hydroxyurea has been FDA approved for the treatment of sickle cell disease for patients ages 2 years and above but NHLBI and ASH Guidelines recommend it be offered to children as young as age 9 months.

Background: Sickle cell anemia (SCA) is associated with cognitive challenges that often worsen as children age. Previous work has established relationships between hematological markers of disease severity (i.e., hemoglobin concentration) and various neurological outcomes, including cognitive impairment. However, most studies have related static, often isolated hemoglobin concentration (Hb) values obtained from a single time-point closest to data collection. Studies of pediatric patients with phenylketonuria and Type I diabetes have demonstrated that longitudinal change and variability in phenylalanine and glucose, respectively, are better indicators of neurological and cognitive outcomes than a single value alone. Our study aimed to be the first study of pediatric patients with SCA to examine the extent to which indices of Hb control (e.g., lifetime average and variability), collected routinely in this patient group, may provide additional prognostic information. Methods: Data were collected from pediatric patients (aged 4-18 years at enrolment) with and without SCA enrolled on the Sleep Asthma Cohort-III (SAC-III) follow-up study. SAC is a mixed retrospective-prospective study assessing the impact of nocturnal oxygen desaturation on SCA complications. The present investigation assessed participants (see Figure 1 for complete participant demographics) who underwent cognitive evaluation using Wechsler scales measuring domains of IQ, processing speed (i.e., processing speed index [PSI] and Cancellation subtest), and executive function (working memory index [WMI]). Participant demographics and appropriate medical data and history (i.e., hydroxyurea therapy, silent infarction) were obtained via questionnaires and analysis of medical records. Hb (d/L) measures assessed included average lifetime values (i.e., mean and median), variability over the lifetime (i.e., standard deviation), and the single value obtained closest to data collection. Results: Correlation analyses indicated a strong positive relationship between the mean and median Hb values along with large positive associations between the average and contemporaneous values. Small non-significant correlations were demonstrated between variability and average Hb values (see Figure 1). Initial hierarchical linear regression analyses demonstrated that neither hydroxyurea use nor silent infarct (SCI) status were predictors of any cognitive outcomes or Hb values, so they were not included in any further analyses. Separate regression analyses for each cognitive outcome found that mean lifetime Hb values was the only significant predictor of IQ (p = .04, η 2 = .13) and the Cancellation subtest (p = .005, η 2 = .22). Mean lifetime Hb values approached significance for PSI (p = .09, η 2 = .08), but was not a predictor for WMI (p = .33, η 2 = .03). Conclusion: Our study demonstrated that despite strong correlations between Hb obtained closest to testing and average lifetime values (i.e., rs = .64 and .69), only lifetime Hb predicted cognitive outcomes, particularly processing speed scores from the Cancellation subtest. Variability was not strongly related to other indices of Hb control and did not predict any cognitive outcomes. These results mirror those obtained from other pediatric populations indicating that static, one time values may not best represent clinical manifestations of chronic illness, and the choice of Hb value can differentially influence research study results and clinical prognosis. Future longitudinal work in larger samples is needed, but Hb obtained over the lifetime appears to provide a more precise picture of patients' cognitive developmental trajectory than a single contemporaneous Hb value alone. Figure 1 Figure 1. Disclosures Kirkham: Bluebird Bio: Honoraria; Novartis: Honoraria; Global Blood Therapeutics: Consultancy. Howard: Imara: Consultancy, Honoraria; Global Blood Therapeutics: Consultancy; Novartis: Consultancy, Honoraria; Resonance Health: Honoraria; Novo Nordisk: Consultancy; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Consultancy; Bluebird Bio: Research Funding.

Background: Sickle cell disease (SCD) is associated with medical challenges that often worsen for adolescents and young adults (AYA) when caregivers begin to transfer responsibility for care. Living with SCD requires self-management and self-efficacy and is a critical concern for AYA as they navigate complex medical systems. However, previous research indicates that AYA with SCD often lack the ability, confidence, and skills to manage their disease effectively. As most AYA with SCD are now "technology natives," mobile health (mHealth) holds considerable promise for assessing and changing behaviors to improve health outcomes. In a previous feasibility and acceptability study, AYA with SCD provided qualitative feedback that they would use mHealth (a co-designed mobile app) and that it was beneficial for tracking health behaviors. Thus, we integrated the mHealth app into a group intervention (SCThrive) and hypothesized that more engagement with the mHealth app would result in increased self-management and self-efficacy for AYA with SCD. Methods: Our analysis from a single-site, randomized control trial (NCT02851615) assessed data from only AYA in the treatment arm (N = 26) who received the SCThrive intervention and used the mHealth app. The sample included AYA with SCD aged 13 to 21 years (Mage = 16.7 years; 54% female; 46% HbSS genotype; all African American/Black) who received six-weekly group sessions (3 in-person, 3 online). All SCThrive participants were provided with the mobile app (iManage) on an iPad. The Transition Readiness Assessment Questionnaire (TRAQ-5) assessed self-management skills and the Patient Activation Measure (PAM-13) assessed self-efficacy at baseline and posttreatment. We also assessed engagement (logins), confidence and completion of self-management goals (e.g., exercising, take medications), pain diary entries, and mood symptoms recorded on the iManage app (see Figure 1). Results: Preliminary analyses indicated that most AYA with SCD logged on to the iManage app (Mlogins = 7.8, SD = 9.1, range = 1 - 45) and viewed their pain diary (Mviews = 5.7, SD = 9.1, range = 1 - 45) at least once a week. Eighty-eight percent of AYA saved a pain diary entry and the most commonly used strategies for managing pain episodes were resting (22%), drinking water (19%), and using distraction (8%). AYA viewed their self-management goals about once every 11 days (Mdays = 11.24, SD = 13, range = 0 - 57). All AYA created (Mgoals = 5.7, SD = .72, range = 4 - 7), but only 54% of AYA completed at least one self-management goal. Of the 149 self-management goals created by the entire sample, only 37 (25%) were recorded as completed. AYA with a confidence level of 7 or lower were least likely to complete their self-management goals (14%) (see Figure 2). Correlation analyses demonstrated that logging on to the iManage app more frequently was associated with completing more self-management goals (r = .38), documenting pain symptoms more frequently (r = .54), and lower mood ratings (r = .54). Primary analyses demonstrated that after controlling for scores at baseline, the number of logins to the iManage app (p = .08, η2 = .13) predicted self-efficacy (PAM-13) and (p = .05, η2 = .17) self-management skills (TRAQ-5). Completing more self-management goals on the iManage app did not predict scores on the PAM-13, but, surprisingly, predicted lower scores (less self-management) on the TRAQ-5 (p = .08, η2 = .14). Conclusion: Lessons learned from our study indicate that it can be challenging to maintain engagement in mHealth for AYA with SCD, but for those who do engage there are significant benefits related to self-management goals, documenting pain symptoms, and mood. Supporting hypotheses, engaging more with the iManage app was related to higher-reported self-efficacy and self-management skills. Some AYA engaged with the app infrequently and did not create or complete self-management goals; others were "super users" and logged into the app daily. Increasing the frequency of reminder messages, encouraging more interactions with peers, and tailoring the opportunity to earn incentives are potential modifications for future interventions. However, our findings indicate that a mHealth app can be effectively integrated into a clinical trial and is related to positive outcomes. Although there are challenges to address, mHealth has the potential to bring about changes in behavior and improve health in the SCD population. Disclosures No relevant conflicts of interest to declare.

Background: Sickle cell disease (SCD) is a genetic disorder that causes significant medical and neurologic morbidity in children. Hydroxyurea (HU) is the primary medication used to prevent these complications. National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend offering HU to children as young as 9 months of age with SCD (HbSS or HbSB0 thalassemia) using a shared decision-making approach. Although HU has proven efficacious it remains underutilized and caregivers report that they are not always actively involved in the decision to initiate this therapy. Reasons for limited HU uptake likely include lack of clinician knowledge and training and negative caregiver perceptions. Thus, we developed the Engage-HU trial as a novel approach to address HU utilization barriers. A critical consideration for this trial was that SCD primarily affects individuals of African and Hispanic/Latino descent. In these minority populations, intervention trials are sometimes terminated early because of recruitment difficulties related to mistrust of research, caregiver burden, and transportation issues. As such, the Engage-HU trial design included best-practice strategies for recruiting people of color in research. This study describes these strategies, the initial recruitment plan, preliminary recruitment outcomes and strategies, and our procedural adaptations. Study Design and Methods: Engage-HU is a randomized control trial (NCT03442114) to assess how clinicians can engage caregivers in a shared discussion that considers their values and preferences and includes evidence that supports HU. Engage-HU compares two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD: 1) the American Society of Hematology Pocket Guide, and 2) the HU Shared-Decision Making (H-SDM) Toolkit. The study aims to recruit 174 caregivers and evaluate the effectiveness of the dissemination methods on patient-centered outcomes (caregiver confidence in decision-making and perceptions of experiencing shared decision-making) as well as HU uptake and child health outcomes. Eligible children are aged 0 to 5 years, candidates for HU, and their caregiver has not made a decision about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a stepped-wedge design. Data will be analyzed based on the intent-to-treat principle. All participants will remain in the arm of the study to which they were randomized, regardless of whether or not they receive the assigned dissemination method. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using a linear mixed effects regression model with a robust variance estimator and maximum likelihood estimation with observations clustered within site. The Engage-HU trial includes adaptations to increase recruitment such as tailored messaging, a relational recruitment approach, streamlined data collection, and a Stakeholder Advisory Committee. However, even with these adaptations, the first 6-months of the trial yielded lower than anticipated recruitment. Rather than terminate the trial or accept low enrollment, the research team implemented a series of recruitment strategies to address barriers including helping to improve research coordinator knowledge of the study purpose and adjusting no-show and follow-up procedures (e.g., calls to families after missed appointments and reminder calls before appointments). Site clinicians and clinic staff were provided with additional training so they could give more context about Engage-HU to caregivers and the study principal investigator led monthly "all coordinator" calls to provide support by sharing updates and experiences about successful recruitment. Implementation of these strategies resulted in triple the number of enrollments over the next 7-months compared to the previous 6-months (Table 1). Our goal in sharing this information is to provide lessons learned that can be implemented in future trials with the systematically underserved SCD population. It is also anticipated that methods described here may also inform clinical approaches to better engage caregivers of young children around critical clinical conversations, such as initiating medications like HU. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; RiverVest: Consultancy; Novimmune: Research Funding; Celgene: Consultancy; Tioma Therapuetics: Consultancy; Amphivena Therapeutics: Research Funding; WUGEN: Current equity holder in private company; Cell Works: Consultancy; Incyte: Consultancy. Smith-Whitley:Prime: Other: Education material; Celgene: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Neumayr:Emmaus: Consultancy; Bayer: Consultancy; CTD Holdings: Consultancy; Pfizer: Consultancy; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Micelle: Other: Site principal investigator; GBT: Other: Site principal investigator; PCORI: Other: site principal investigator; Novartis: Other: co-investigator; Bluebird Bio: Other: co-investigator; Sangamo Therapeutics: Other; Silarus: Other; Celgene: Other; La Jolla Pharmaceuticals: Other; Forma: Other; Imara: Other; National Heart, Lung, and Blood Institute: Other; Health Resources and Services Administration: Other; Centers for Disease Control and Prevention: Other; Seattle Children's Research: Other. Yates:Novartis: Research Funding. Thompson:Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; BMS: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding.

Children with sickle cell disease (SCD) experience disproportionately high rates of psychological problems. Our goal was to examine the clinical utility of psychological screening measures to identify children with such problems in medical settings. Caregivers completed screening measures assessing social-emotional problems, ADHD symptoms, executive dysfunction, and health-related quality of life (HRQOL) for children with SCD (receiving either chronic blood transfusion or hydroxyurea) and their siblings. Our findings demonstrated that screening measures identified clinically elevated symptoms in children with SCD that had not been previously reported. Scores for siblings were for the most part in the normal range. The number of days hospitalized (but not cerebral infarct status) predicted higher scores, emphasizing the challenges associated with SCD complications. Overall, our findings support the notion that screening measures reduce the need for reliance on medical provider judgment for psychological referrals and increase equitability in access to services. Early identification resulting in early intervention has contributed substantially to improved psychological functioning in many contexts, and it is thus likely that such improvements would also be achieved in this uniquely vulnerable population.

OBJECTIVES: Sickle cell disease (SCD) is the most prevalent inherited hematological disorder and affects 100,000 individuals in the United States. Pain is the most common cause of emergency department (ED) visits in the SCD population, which profoundly affects quality of life. Vitamin D supplementation is a potential target for reducing pain. Thus, the goal of the present study was to identify the prevalence of vitamin D deficiency and explore the relationship between vitamin D supplementation and ED visits in pediatric patients with SCD. DESIGN: We conducted a retrospective chart review of 110 patients with SCD aged 8 to 16 years who had at least one ED visit for SCD pain during the 6-year study period. Patients were categorized into three vitamin D supplementation groups: patients who did not receive supplementation, patients supplemented with 25-hydroxyvitamin D levels (< 30 ng/mL), and patients supplemented with at least one sufficient 25-hydroxyvitamin D level (≥ 30 ng/mL). RESULTS: Overall, 45% of patients were vitamin D deficient. Only 20% of patients had sufficient vitamin D levels. This number increased to 55% when examining only patients who did not receive vitamin D supplementation. For patients supplemented with vitamin D, the number of ED visits was significantly lower after they reached the sufficient range (≥ 30 ng/mL), p = .03. CONCLUSIONS: Our findings indicate that reductions in the number of pain-related ED visits may be achieved by normalizing 25-hydroxyvitamin D levels with supplementation. In addition, findings highlight the need for screening and vitamin D supplementation being incorporated into routine care for pediatric patients with SCD.

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non-SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3-7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, χ2 (1) = 17.8, P < .0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD.

Phenylketonuria (PKU) is a recessive disorder characterized by disruption in the metabolism of the amino acid phenylalanine (Phe). Prior research indicates that individuals with PKU have substantial white matter (WM) compromise. Much less is known about gray matter (GM) in PKU, but a small body of research suggests volumetric differences compared to controls. To date, developmental trajectories of GM structure in individuals with PKU have not been examined, nor have trajectories of WM and GM been examined within a single study. To address this gap in the literature, we compared longitudinal brain development over a three-year period in individuals with PKU (n = 35; 18 male) and typically-developing controls (n = 71; 35 male) aged 7–21 years. Using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI), we observed whole-brain and regional WM differences between individuals with PKU and controls, which were often exacerbated with increasing age. In marked contrast with trajectories of WM development, trajectories of GM development did not differ between individuals with PKU and controls, indicating that neuropathology in PKU is more prominent in WM than GM. Within individuals with PKU, mediation analyses revealed that whole-brain mean diffusivity (MD) and regional MD in the corpus callosum and centrum semiovale mediated the relationship between dietary treatment compliance (i.e., Phe control) and executive abilities, suggesting a plausible neurobiological mechanism by which Phe control may influence cognitive outcomes. Our findings clarify the specificity, timing, and cognitive consequences of whole-brain and regional WM pathology, with implications for treatment and research in PKU., Highlights • Individuals with PKU exhibited widespread, age-related white matter compromise. • Developmental trajectories of gray matter were comparable for PKU and controls. • Within PKU, white matter compromise influenced cognitive outcomes.

This case study presents an overview of the major challenges and successes encountered assessing whether working memory performance was impaired in healthy individuals with high levels of anxiety when their cortisol levels increased after acute stress. The study presented used an experimental design and quantitative data analysis using a moderated mediation model. In the case study that follows, we describe anxiety disorders, stress and the resulting physiological responses, and how anxiety and stress can impair working memory performance. In addition, we reflect on the use of healthy college students in research that has clinical implications, how to design a study that uses an experiment stressor, and the potential pitfalls of salivary cortisol collection and analysis. We also discuss the changes we would implement if we were to conduct similar research in the future. This case study highlights the use of an experimental design and statistical modeling to answer interesting questions about human behavior.

Anxiety is an aversive emotional state characterized by perceived uncontrollability and hypervigilance to threat that can frequently cause disruptions in higher-order cognitive processes like working memory. The attentional control theory (ACT) predicts that anxiety negatively affects the working memory system.This study tested the association between anxiety and working memory after the addition of stress and measured the glucocorticoid, cortisol. To better understand this relationship, we utilized a moderated mediation model.Undergraduate students from a public university (N = 103) self-reported their anxiety levels. Participants first completed a short-term memory test. During and after a forehead cold pressor task (stress vs. control procedure) participants completed a working memory test. Salivary cortisol was taken at baseline and after the last working memory test.Overall, acute stress had no effect on working memory. However, we found that anxiety levels mediated the influence of condition (stressed vs. control) on working memory, but only among those individuals who had high cortisol levels after exposure to acute stress, supporting a moderated mediation model.These results imply that activation of the hypothalamic-pituitary-adrenal axis was necessary for working memory impairment in anxious individuals. These results provide support for the ACT.

Background: Although hydroxyurea (HU) is an effective disease modifying treatment for sickle cell disease (SCD), uptake remains low in pediatric populations in part due to parental concerns such as side-effects and safety. NHLBI Guidelines recommend shared decision making for HU initiation to elicit family preferences and values; however, clinicians lack specific training. A HU shared decision-making (H-SDM) toolkit was developed to facilitate such discussions (NCT03442114). It includes: 1) decision aids to support parents (brochure, booklet, video narratives, and an in-visit issue card [featuring issues parents reported as key to decision-making about HU]); 2) quality improvement tools to monitor shared decision-making performance; and 3) a curriculum to train clinicians in advanced communication skills to engage parents in shared decision-making. This abstract describes the development and preliminary evaluation of the virtual reality (VR) component of the clinician curriculum. Objectives: The goals are to: 1) describe the development of a VR simulation for training clinicians in advanced communication skills, and 2) present preliminary data about its tolerability, acceptability, and impact. Methods: Immersive VR simulations administered via a VR headset were created. The VR environment was designed to replicate a patient room, and graphical character representatives (avatars) of parents and patients were designed based on common demographics of patients with SCD (Figure 1). During simulations, the provider verbally counseled the avatars around HU initiation with avatars' verbal and non-verbal responses matched appropriately. The H-SDM in-visit issue card was incorporated into the virtual environment to reinforce practice with this tool. The VR curriculum was piloted for initial acceptability with parents of a child with SCD and clinicians at a children's hospital. Evaluation: Hematology providers participated in the workshop training that included information on facilitating shared decision-making with subsequent deliberate practice of skills through VR simulations. Each provider completed at least one VR simulation. The view through the VR headset was displayed on to a projector screen so others could view the virtual interaction. Debriefing occurred regarding use of communication skills and utilization of the issue card. To assess tolerability, providers reported side effects related to participation. To assess acceptability, providers completed a modified version of the Spatial Presence Questionnaire and described their experience. Impact was assessed by self-report on a retrospective pre-post survey of confidence in specific communication skills using a 5-point scale (from not confident at all to very confident). Differences in confidence were assessed using Wilcoxon Signed-ranks tests. Results: Nine providers (5 pediatric hematologists and 4 nurse practitioners at 3 children's hospitals) participated. Tolerability: The VR experience was well tolerated with most providers reporting no side effects (Table 1). Acceptability: All providers agreed or strongly agreed that the VR experience captured their senses and that they felt physically present in the VR environment. Providers described the experience as "enjoyable", "immersive", and "fun". One provider noted, "It (the VR simulation) put me in clinic to experience what it felt like to discuss HU and use the tool." Impact: Providers' self-reported confidence significantly improved after VR simulations on 4 of 5 communication skills: confirming understanding, Z =1.98, p = .05, r = .44, eliciting parent concerns/values, Z = 2.22, p = .03, r = .50, using an elicit-provide-elicit approach, Z =1.8, p = .02, r = .50, minimizing medical jargon, Z = 1.8, p = .07, r = .40, and using open-ended questions, Z =1.98, p = .05, r = .44. Median scores changed by one-point for all responses and effects were medium to large (see Figure 2). Discussion: The VR curriculum was rated as immersive, realistic, and well-tolerated. Providers endorsed it as a desirable training method. Self-report of confidence in shared decision making-related communication skills improved following completion of VR simulation. Thus, initial data support that VR may be an effective method for educating providers to engage parents in shared decision making for HU. Disclosures Quinn: Amgen: Other: Research Support; Celgene: Membership on an entity's Board of Directors or advisory committees.

Background: The FDA approved hydroxyurea (HU) for the treatment of sickle cell disease (SCD) in children because it was deemed a safe and efficacious treatment. HU modifies the course of the disease, reduces complications, improves survival, and has few long-term side effects. Despite these benefits, HU uptake remains low for young children. Over 75% of patients who could benefit from HU do not receive the treatment. NHLBI clinical practice guidelines recommend use of shared decision making for HU initiation but currently, there is no "gold standard" for hematology providers to follow when beginning their discussion about HU. Thus, there is likely a gap between care guidelines and clinical practice. A first step in closing this gap is to better understand the current practice utilized by hematology providers when discussing HU as a therapeutic option. Objectives: The goal of the present study is to describe current practice used by hematology providers when discussing HU with parents of young children with SCD (0 - 5 years of age), Our primary aims are: 1) Map the process of offering HU to identify common themes, overlaps, and variations, 2) Examine the impact of a brief video presentation about the NHLBI HU guidelines on provider knowledge and comfort levels. Methods: The dissemination of methods to increase adherence to NHLBI HU guidelines are being evaluated as part of a clinical trial (NCT03442114). Hematology providers at 6 children's hospitals serving young patients with SCD completed process maps that described their current practice for discussing HU initiation with parents. Twenty five hematology providers at 10 institutions across the United States viewed a video didactic presentation on the NHLBI HU guidelines for SCD. Knowledge and comfort regarding discussing HU was assessed using a 10-point scale before and after the video. We also collected data on provider demographics, years practicing, and percentage of patients seen with SCD each week in their practice. Results: Preliminary analyses identified common themes (see Table 1 for provider characteristics). All 6 sites reported that labs and vitals were taken prior to the visit so they could be reviewed with the family. A medical doctor, nurse practitioner, or licensed practical nurse (LPN) led the HU initiation discussion. The majority of sites give their families HU-related materials to take home after the discussion and followed-up regarding the family's decision at the next clinic visit (i.e. planned for a two-visit HU initiation process). Variations identified included providing HU-related materials to the family prior to the visit, when the discussion would occur, and whether NHLBI HU guidelines framed the discussion (Figure 1). Paired samples t-tests assessed for change in medical provider reported HU knowledge and comfort before and after the SCD didactic presentation. Data revealed that there were no differences in provider comfort,t(21) = .77, p = .45, d = .03. In contrast, there was a trend towards a significant increase in medical provider knowledge from before (M = 8.4, SD = 2.3) to after (M = 8.7, SD = 2.1) the presentation, t(21) = 1.8, p = .08, d = .11, small effect. Correlation analyses determined that higher baseline provider knowledge and comfort with HU were significantly correlated with seeing more SCD patients on a weekly basis (Figure 2). Discussion: This study identified common elements of clinical practice for HU initiation in young children with SCD, but variations were also revealed. All institutions in the study obtained lab work prior to the discussion with the family; however the provider initiating the discussion varied by site (e.g., 1 site used an LPN). Most institutions plan for a two-visit discussion as families may not be ready to make a decision during the first visit but feel more supported over time. It is critical that patients and families make their decision based on SCD-specific HU information. Study data indicated that a brief didactic presentation elicited a small improvement provider HU knowledge. Moreover, exposure to the SCD population was strongly related to knowledge and comfort with HU, suggesting that hematology providers with more experience working with patients with SCD may be in the best position to initiate discussions about HU. The incorporation of decision support tools might help to support hematology providers and reduce the variation across institutions observed in our study. Disclosures King: Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; RiverVest: Consultancy; Novimmune: Research Funding; WUGEN: Equity Ownership; Celgene: Consultancy; Cell Works: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Amphivena Therapeutics: Research Funding; Bioline: Consultancy; Incyte: Consultancy. Piccone:Hemex Health, Inc.: Patents & Royalties. Neumayr:Terumo: Research Funding; Apopharma: Consultancy; PCORI: Research Funding; NHLBI: Research Funding; Bluebird Bio: Research Funding; Sancillo: Research Funding; Seattle Children's Research Grants: Research Funding; Doris Duke Foundation: Research Funding; Novartis: Research Funding; Bayer: Consultancy; Celgene: Research Funding; Imara: Research Funding; Sangamo: Research Funding; Silarus: Research Funding; Pfizer: Consultancy, Research Funding; Emmaus: Consultancy; CTD Holdings: Consultancy; GBT: Research Funding; La Jolla Pharmaceuticals: Research Funding; HRSA: Research Funding; CDC: Research Funding. Meier:CVS Caremark: Consultancy.

The effects of pain on memory are complex, and little is known about the vulnerability of working memory (WM) performance when individuals complete a WM test while concurrently experiencing pain. Here, we subjected 78 healthy nonsmoking participants to either acute pain or a control condition while we administered a WM test. In this context, we also tested WM 20 minutes after pain in order to determine if timing of pain affected WM performance, and assessed objective and subjective measures of pain. We hypothesized that pain would impair WM performance during pain. Further, women's WM performance would be impaired more than men. Importantly, there was an interaction between gender and condition, with women exposed to pain experiencing impairments during but not after the cold pressor task. Our data imply that timing and gender are critically important in whether acute pain is costly to WM performance. Our findings have interesting clinical, professional, and educational implications, and understanding the influence of pain could help to improve the interpretation of WM tests in these diverse settings. Perspective Results of this study support the growing body of work that attests to the detrimental effect of pain on WM performance. Further, this study provides new evidence that concurrently experiencing cold pressor pain impairs WM in regularly menstruating women and women taking a contraceptive.

Numerous studies have established a link between distress tolerance and smoking cessation outcomes. The present study examined whether smoking status affected physical distress tolerance, and considered this question separately for men and women. The sample was comprised of healthy adults, 56 smokers (63% male) and 58 nonsmokers (62% female). The pain stimulus was a cold pressor task. Outcome variables were seconds immersed in cold water when pain was first reported (threshold), and total seconds immersed in cold water (tolerance). Participants verbally reported their pain rating on a 0-100 scale after the task, and then completed the McGill Pain Questionnaire-Short Form. Smokers displayed lower pain tolerance than nonsmokers (p = .045), and women displayed lower pain tolerance than men (p = .017). Female smokers had significantly lower pain tolerance than other groups (p = .001). There were no significant differences in pain threshold or pain perception by smoking status or gender (p > .05). Lower physical distress tolerance could place female smokers at risk for difficulty in quitting smoking. This population needs additional research to better understand their unique pain experience and how physical distress tolerance impacts their smoking cessation outcomes.

The present study examined the association between positive traits, pain catastrophizing, and pain perceptions. We hypothesized that pain catastrophizing would mediate the relationship between positive traits and pain. First, participants (n = 114) completed the Trait Hope Scale, the Life Orientation Test- Revised, and the Pain Catastrophizing Scale. Participants then completed the experimental pain stimulus, a cold pressor task, by submerging their hand in a circulating water bath (0º Celsius) for as long as tolerable. Immediately following the task, participants completed the Short-Form McGill Pain Questionnaire (MPQ-SF). Pearson correlation found associations between hope and pain catastrophizing (r = −.41, p < .01) and MPQ-SF scores (r = −.20, p < .05). Optimism was significantly associated with pain catastrophizing (r = −.44, p < .01) and MPQ-SF scores (r = −.19, p < .05). Bootstrapping, a non-parametric resampling procedure, tested for mediation and supported our hypothesis that pain catastrophizing mediated the relationship between positive traits and MPQ-SF pain report. To our knowledge, this investigation is the first to establish that the protective link between positive traits and experimental pain operates through lower pain catastrophizing.

We tested the hypothesis that brain white matter integrity mediates the relationship between phenylalanine (Phe) control and executive abilities in children with phenylketonuria (PKU; N = 36). To do so, we examined mean diffusivity (MD) from diffusion tensor imaging (DTI) in two white matter brain regions (posterior parietal–occipital, PPO; centrum semiovale, CSO) and lifetime phenylalanine (Phe) exposure; the executive abilities examined included verbal strategic processing, nonverbal strategic processing, and working memory. Mediation modeling showed that MD in the PPO and CSO mediated the relationship between Phe exposure and nonverbal strategic processing, MD in the CSO mediated the relationship between Phe exposure and verbal strategic processing, and MD in the PPO mediated the relationship between Phe exposure and working memory. These exploratory findings demonstrate the importance of using sophisticated modeling procedures to understand the interplay among metabolic control, neural factors, and functional outcomes in individuals with PKU.