Feasibility and preliminary efficacy of the Balance Program to reduce pain-related disability in pediatric sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) pain is associated with functional impairment, and treatment is often limited to pharmacological approaches with unwanted side effects. Although behavioral interventions exist for non-SCD pain populations, interventions designed to address pain-related impairment in SCD are lacking. METHODS: Twenty youth (9-17 years) with SCD completed a four-week telemedicine pain intervention (NCT04388241). Participants and caregivers completed baseline and post-intervention PROMIS pain measures and the Treatment Evaluation Inventory-Short Form (TEI-SF). Descriptive analyses assessed feasibility and acceptability. Reliable Change Index analyses assessed for significant post-intervention changes in pain functioning. Paired t test analyses compared baseline and post-intervention opioid prescription fills. RESULTS: All participants completed at least one treatment session. Eighteen (90%) youth completed all sessions. Youth (100%) and caregivers (94%) rated the intervention as moderately or highly acceptable on the TEI-SF. Forty-seven percent of caregivers and 44% of youth reported reliably significant improvements in pain interference after the intervention (median T-score differences: 24.8 and 23.5, respectively). Sixty-five percent of caregivers (T-score improvement difference: 19.3) and 31% of youth (T-score improvement difference: 32) reported improvements in pain behaviors. There was no significant difference in opioid prescription fills pre- and post-intervention (P > 0.05). CONCLUSIONS: The Balance Program is feasible, highly acceptable, and can be delivered remotely to reduce barriers to care. Approximately half of youth and caregivers reported significant declines in pain interference following the intervention, with substantial improvements in functioning for treatment responders. Behavioral pain interventions are important adjunctive treatments to uniquely address functional impairment associated with acute and chronic pain in SCD.

Neurocognitive and emotional factors predict pain-related healthcare utilization in children with sickle cell disease.

BACKGROUND: Youth with sickle cell disease (SCD) experience increased rates of neurocognitive and emotional difficulties. Cross-sectional studies suggest neurocognitive and emotional functioning are associated with health outcomes in SCD. We investigated whether neurocognitive and emotional factors predicted future pain-related healthcare utilization in children with SCD. PROCEDURE: Total 112 youth with SCD between ages 7 and 16 years reported sociodemographics and completed measures of neurocognitive functioning and emotional well-being. The number of emergency department (ED) visits and hospitalizations for pain 1 and 3 years after enrollment were determined by chart review. RESULTS: The mean age of participants was 10.61 years (standard deviation = 2.91), with most being female (n = 65; 58%). Eighty-three (74%) participants had either HbSS or HbSß0 thalassemia. Regression analyses showed that attention significantly predicted ED visits and hospitalizations for pain at 1 and 3 years after enrollment (all p-values ≤ .017), such that poorer attention was associated with higher healthcare utilization. Lower emotional quality of life also predicted more ED visits for pain at 3 years (b = -.009, p = .013) and hospitalizations for pain at 3 years (b = -.008, p = .020). CONCLUSIONS: Neurocognitive and emotional factors are associated with subsequent healthcare use in youth with SCD. Poor attentional control might limit implementation of strategies to distract from pain or could make disease self-management behaviors more challenging. Results also highlight the potential impact of stress on pain onset, perception, and management. Clinicians should consider neurocognitive and emotional factors when developing strategies to optimize pain-related outcomes in SCD.

Sluggish Cognitive Tempo in Pediatric Sickle Cell Disease.

Background: Sickle cell disease (SCD) imparts risk for a range of neurodevelopmental and neurocognitive disorders. Sluggish cognitive tempo (SCT) is a distinct syndrome that often co-occurs with attention-deficit/hyperactivity disorder (ADHD) but has not been described in SCD. We investigated the reliability and validity of a SCT measure in SCD and examined associations with biopsychosocial risk factors and functional outcomes. Materials and Methods: Caregivers (n = 85) of children with SCD ages 7-16 reported on socio-demographics and the Kiddie-Sluggish Cognitive Tempo (K-SCT) measure, Behavior Rating Inventory of Executive Function, and Conners 3. Disease-related characteristics were extracted from health records. Results: The K-SCT demonstrated excellent internal consistency (α = 0.92) and test-retest reliability (r = 0.82, p < 0.001). K-SCT scores were correlated with ADHD-Inattention (r = 0.64, p < 0.001) and ADHD-Hyperactive/Impulsive (r = 0.46, p < 0.001) scores, as well as functional outcomes, including learning problems (r = 0.69, p < 0.001). In multivariate analyses controlling for ADHD symptoms, SCT accounted for unique variance in learning (b = 9.67, p < 0.01) and executive functioning (b = 5.93, p < 0.01). Nearly all participants (93%) with elevated levels of co-occurring SCT and ADHD-Inattention symptoms had significant learning problems. Conclusion: The K-SCT is a reliable and valid measure of SCT in SCD. SCT symptoms are associated with learning difficulties even after controlling for ADHD symptoms. Further research is needed to understand the biopsychosocial factors that lead to SCT symptoms in SCD and examine long-term implications of SCT.

Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease.

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r = -0.656, P = 0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r = -0.551, P = 0.001), subgenual ACC (r = -0.540, P = 0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P = 0.047; right: P = 0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.

Acupuncture as an Adjunctive Treatment for Pain in Hospitalized Children With Sickle Cell Disease.

CONTEXT: Acute episodes of pain associated with sickle cell disease (SCD) account for over 100,000 hospitalizations and expenses of nearly one billion dollars annually in the U.S. New treatment approaches are needed as the current opioid based therapy is often inadequate in controlling pain, resulting in prolonged inpatient stays, and high rates of readmission. OBJECTIVES: To evaluate acceptability of acupuncture as an adjunctive therapy and explore the impact of acupuncture on pain related outcomes in a population of youth with SCD hospitalized for management of acute pain. METHODS: This IRB approved single center study recruited youth with SCD (9-20 years) who were hospitalized for management of acute pain into either the acupuncture group or controls. Both groups also received standard pain management therapies. RESULTS: Participants in the acupuncture (n = 19) and control (n = 10) group were comparable in clinical characteristics. Acupuncture had an acceptability rate of over 66% and was tolerated well without any side effects. Acupuncture was associated with reduction in pain scores (6.84-5.51; P < 0.0001). Acupuncture group demonstrated a trend toward lower length of stay and readmission rates, but these were not statistically significant. Opioid use was not different between the groups. Treatment Evaluation Inventory survey showed high rates of satisfaction with acupuncture. CONCLUSION: Acupuncture was broadly accepted and well-tolerated in our study population. Acupuncture treatment was associated with a statistically significant and clinically meaningful reduction in pain scores immediately following the treatments, and a trend towards a reduction in length of stay and readmission for pain.

A Randomized Controlled Trial of Working Memory Training in Pediatric Sickle Cell Disease.

OBJECTIVE: Youth with sickle cell disease (SCD) are at risk for neurocognitive deficits including problems with working memory (WM), but few interventions to improve functioning exist. This study sought to determine the feasibility and efficacy of home-based, digital WM training on short-term memory and WM, behavioral outcomes, and academic fluency using a parallel group randomized controlled trial design. METHODS: 47 children (7-16 years) with SCD and short-term memory or WM difficulties were randomized to Cogmed Working Memory Training at home on a tablet device (N = 24) or to a standard care Waitlist group (N = 23) that used Cogmed after the waiting period. Primary outcomes assessed in clinic included performance on verbal and nonverbal short-term memory and WM tasks. Secondary outcomes included parent-rated executive functioning and tests of math and reading fluency. RESULTS: In the evaluable sample, the Cogmed group (N = 21) showed greater improvement in visual WM compared with the Waitlist group (N = 22; p = .03, d = 0.70 [CI95 = 0.08, 1.31]). When examining a combined sample of participants, those who completed ≥10 training sessions exhibited significant improvements in verbal short-term memory, visual WM, and math fluency. Adherence to Cogmed was lower than expected (M = 9.07 sessions, SD = 7.77), with 19 participants (41%) completing at least 10 sessions. Conclusions: Visual WM, an ability commonly affected by SCD, is modifiable with cognitive training. Benefits extended to verbal short-term memory and math fluency when patients completed a sufficient training dose. Additional research is needed to identify ideal candidates for training and determine whether training gains are sustainable and generalize to real-world outcomes.

Cognitive Functioning and Educational Support Plans in Youth With Sickle Cell Disease.

Children with sickle cell disease (SCD) face academic challenges because of direct and indirect disease-related events. This study examined the proportion of youth with SCD with educational plans and whether cognitive functioning is associated with educational support. Ninety-one youth (7 to 16 y) with SCD completed the WISC-V; caregivers reported educational support (504 Plan/Individualized Education Program) and completed the Behavior Rating Inventory of Executive Function. χ2 square and t test analyses explored whether overall intelligence (full-scale intelligence quotient [FSIQ]), relative weaknesses in processing speed and working memory (> 1SD below FSIQ), and parent-reported executive functioning were associated with educational plans. Participants with a FSIQ<90 were more likely to have support (74%) compared with youth with a FSIQ≥90 (47%; P=0.012). Those with FSIQ≥90 and FSIQ=80 to 89 were less likely to have support (47%, 58%, respectively) compared with those with FSIQ≤79 (89%; P=0.004). Relative weaknesses in processing speed were associated with educational support (83% vs. 52%, P=0.018) as well as behavioral aspects of executive functioning (Ps<0.05). Despite universal eligibility for a 504 Plan, 42% of youth with SCD in our sample did not have educational support. Significant deficits in intellectual functioning, processing speed, and parent-observed executive functioning are associated with having a plan, but children with subtle deficits seem less likely to be identified for educational support.

Integrative holistic approaches for children, adolescents, and young adults with sickle cell disease: A single center experience.

CONTEXT: Painful vaso-occlusive crises (VOCs) associated with sickle cell disease (SCD) are the most common cause of morbidity, hospitalizations, and poor quality of life. Additional symptoms such as sleep disturbances, fatigue, and stress are also common. Non-traditional approaches are often used by families, but concerns remain that patients may forgo standard of care effective therapies in favor of dangerous unproven alternatives. OBJECTIVES: To describe a single center experience related to a multidisciplinary integrative medicine clinic within the division of hematology dedicated to children and young adults with SCD. METHODS: The Sickle Cell Integrative Clinic at Children's National Hospital services patients with SCD. The main goal of this clinic is to provide access to non-pharmacologic interventions, and to manage patients' symptoms in a holistic manner along with standard of care management of SCD. This IRB approved study evaluated experiences of both patients and parents who attended this clinic. RESULTS: Thirty-seven unique patients attended this clinic over 2 years and 31 participated in the study. After attending the SCD integrative clinic, the majority of patients reported integrative therapies to be an acceptable way of treating pain and believed these to be effective. Overall, the vast majority (88 %) of patients reported having a positive experience with the therapies offered in the clinic. None of the patients experienced any adverse events related to integrative therapies provided in the clinic. CONCLUSION: Our experience suggests that encouraging conversations and offering safe and potentially effective integrative therapies alongside conventional SCD therapies under medical guidance allows patients to have an open discussion about their beliefs and treatment goals, improves patient satisfaction and can improve outcomes.

Acupuncture for pain management in children with sickle cell disease.

Pain associated with sickle cell disease (SCD) is frequently treated with opioids which have many side effects. There is a need for adjuvant non-opioid therapies that can improve pain control. Acupuncture, an integrative approach, has been shown to be useful in non-SCD pain conditions but has been used to a very limited extent in SCD. In this report we present a single academic pediatric center experience showing acceptability, feasibility and improved pain experience with adjuvant acupuncture therapy in children with SCD and suggest that acupuncture should be explored as a treatment option for managing pain in SCD.

Social-environmental factors and cognitive and behavioral functioning in pediatric sickle cell disease.

Sickle cell disease (SCD), an inherited blood disorder that primarily affects individuals of African descent, is associated with serious medical complications as well as numerous social-environmental risk factors. These social-environmental factors are linked to long-standing social inequities, such as financial hardship and racial discrimination, both of which impact cognitive and behavioral functioning in youth. Previous research on the relationship between social-environmental risk and psychological functioning has primarily relied on non-modifiable, unidimensional measures of socioeconomic status (SES), such as income and parental education, as a proxy for social-environmental risk. The current study aimed to address the limitations associated with typical SES-type measures by comparing the unique and shared association of SES and more targeted and modifiable social-environmental factors (e.g., parent and family functioning) with specific areas of cognitive and behavioral adjustment in pediatric SCD. Seventy children ages 4-8 years old and their parents completed measures of social-environmental risk and psychological adjustment. Exploratory factor analysis indicated parent and family functioning measures were largely independent of SES. Parent and family functioning predicted phonological processing and ADHD symptoms above and beyond SES alone. In addition, the predictive ability of social-environmental risk factors appears to vary by genotype severity for measures of social functioning and math problem-solving ability. Future studies are needed to explore more specific and well-supported models of modifiable social-environmental risk and the relative impact of social-environmental risk on cognitive and behavioral functioning.

Neurocognitive and psychological effects of persistent pain in pediatric sickle cell disease.

BACKGROUND: Pain is a major complication of sickle cell disease (SCD), spanning vaso-occlusive crises and persistent pain. Although it is known that persistent pain is associated with considerable impairment in youth without SCD, little is known about the functional effects of persistent pain in SCD. The current study aimed to (a) characterize persistent pain in youth with SCD and (b) determine the extent to which youth with SCD and persistent pain differ in disease morbidity, functional impairment, and neurocognitive and psychological functioning. PROCEDURE: Eighty-nine participants (ages 7-16) and caregivers completed questionnaires (BRIEF [Behavior Rating Inventory of Executive Function], Conners-3 [Conners-third edition], and PedsQL™-SCD Module, where PedsQL is Pediatric Quality of Life Inventory). Participants completed neurocognitive tests WISC-V [Wechsler Intelligence Scale for Children-fifth edition], WJ-III [Woodcock Johnson Tests of Achievement-third edition], and WIAT-III [Wechsler Individual Achievement Test-third edition]). Youth were classified as having persistent pain if they reported daily pain for 7 days. Chi-square and independent sample t-test analyses were used to assess group differences (those with vs without persistent pain). RESULTS: Patients with persistent pain (n = 18) reported lower health-related quality of life (P = .000). Caregivers were more likely to rate youth with persistent pain as having lower planning/organization abilities (P = .011) and clinically elevated symptoms of defiance/aggression and oppositional defiance (Ps = .00; .01). Patients with persistent pain demonstrated poorer working memory (P = .023) and processing speed (P = .027), and fewer demonstrating reading fluency abilities in the average or above range (P = .026). CONCLUSIONS: Youth with SCD and persistent pain are at risk for psychosocial and neurocognitive impairments, suggesting that persistent pain may be an important indicator of disease burden. Furthermore, disease management may be enhanced by assessing cognitive and psychosocial functioning and incorporating interdisciplinary treatments addressing impairment associated with persistent pain.

Views of parents of children with sickle cell disease on pre-implantation genetic diagnosis.

Pre-implantation genetic diagnosis (PGD) is an option for parents who have a child with sickle cell disease (SCD) to have another child without SCD. We conducted a survey of 19 parents with at least one child with SCD to investigate views on PGD. Before education, 44% of parents were aware of PGD. All parents rated PGD education as important. All parents considering another child also reported interest in using PGD if insurance covered its costs. Parents who have a child with SCD appear to be interested in PGD and educational tools informing this group about PGD should be developed.

Cognitive Abilities Moderate the Effect of Disease Severity on Health-Related Quality of Life in Pediatric Sickle Cell Disease.

Objective: Complications that can arise from sickle cell disease (SCD) have the potential to negatively affect health-related quality of life (HRQL). SCD manifests in varying degrees of severity, but effects on HRQL are not uniform. Cognitive abilities influence HRQL in other pediatric groups, potentially through variability in treatment adherence and psychological coping. This study examined the effect of SCD severity on HRQL and explored cognitive abilities as a moderator of this relationship. Methods: A total of 86 children and adolescents with SCD (ages 7-16 years) completed a cognitive assessment (Wechsler Scale of Intelligence for Children, Fifth Edition), and primary caregivers rated their child's SCD severity and HRQL (PedsQL Sickle Cell Disease Module). A hierarchical linear regression was conducted to evaluate the interactive effect of SCD severity and cognitive functioning on HRQL. Results: Caregiver-rated SCD severity predicted HRQL and cognitive abilities interacted with disease severity to influence HRQL. Youth with milder SCD and cognitive abilities in the average range or higher demonstrated significantly better HRQL compared with youth with mild SCD but below average cognitive abilities. Youth with more severe disease appeared to exhibit similarly low levels of HRQL, with only a minimal influence of cognitive abilities. Conclusions: Cognitive factors modify the effect of SCD severity on HRQL, particularly among youth with milder forms of SCD. Future studies are warranted to clarify the role of cognitive abilities in determining HRQL. Clinicians should monitor youth with milder forms of SCD and limited cognitive abilities for worsening HRQL and opportunities to provide support around disease self-management.

Feasibility of Home-Based Computerized Working Memory Training With Children and Adolescents With Sickle Cell Disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for neurocognitive deficits, yet the literature describing interventions to ameliorate these problems and promote academic achievement is limited. We evaluated the feasibility and preliminary efficacy of a home-based computerized working memory (WM) training intervention (Cogmed) in children with SCD. PROCEDURE: Youth with SCD between the age of 7 and 16 years completed an initial neuropsychological assessment; those with WM deficits were loaned an iPad on which they accessed Cogmed at home. Participants were instructed to work on Cogmed 5 days each week for 5 weeks (25 training sessions). We examined Cogmed usage characteristics and change on WM assessment scores following the intervention. RESULTS: Of the 21 participants (M age = 11.38, SD = 2.78; Mdn age = 10.00, interquartile range [IQR] = 5.00; 52% female) screened, 60% exhibited WM deficits (n = 12) and received the intervention and 50% (n = 6) completed Cogmed. The mean number of sessions completed was 15.83 (SD = 7.73; Mdn = 17.00, IQR = 16.00); females were more likely to complete Cogmed, χ(2) (1) = 6.00, P = 0.01. Participants who reported lower SCD-related pain impact completed more sessions (r = 0.71, P = 0.01). Children who completed Cogmed exhibited improvements in verbal WM, visuospatial short-term memory, and visuospatial WM. CONCLUSIONS: Initial findings suggest Cogmed is associated with WM improvement in youth with SCD; however, adherence was lower than expected. Home-based WM interventions may ameliorate SCD-related WM deficits but strategies are needed to address barriers to program completion.

Posttraumatic growth in children and youth: clinical implications of an emerging research literature.

Posttraumatic growth (PTG), positive change resulting from the struggle with trauma, has garnered significant attention in the literature on adults. Recently, the research base has begun to extend downward, and this literature indicates that youth also evidence PTG-like changes. Researchers have sought to assess the construct, examine its correlates, and understand the factors that contribute to PTG in youth. Drawing from this work, this article considers clinical implications for youth. After briefly describing the PTG construct, its hypothesized process, and its distinction from resilience, the article focuses on key themes in the literature and, with those findings as backdrop, ways in which professionals can facilitate growth in youth who have experienced trauma. This discussion situates PTG within the broader trauma literature and includes specific applications used to date as well as the role of cultural factors. Future directions--salient to practitioners and researchers alike--are considered.