Sleep and fatigue among youth with sickle cell disease: A daily diary study.

Youth with sickle cell disease (SCD) experience disease effects including vaso-occlusive pain crises, poor sleep quality, and fatigue. The present study examines how sleep quality and pain medications impact fatigue in youth with SCD. Daily diaries assessing pain, fatigue, sleep quality, mood, and use of pain medications from 25 youth with SCD ages 11 to 18 years were collected for eight consecutive weeks. Poor sleep quality predicted increases in next-day fatigue levels while controlling for pain and mood. Sleep quality did not moderate the existing temporal relationship between pain and next-day fatigue established by Reinman et al. (2019) as predicted. Non-opioid medications affected ratings of next-day fatigue but opioid medications did not. Sleep quality appears to play an important role in predicting next-day fatigue levels and may be an important target for intervention. Pain medication use did not substantially contribute to prospective fatigue levels among youth, but requires further study.

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.

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.

Association between somatic growth trajectory and cognitive functioning in young children with sickle cell disease.

Children with sickle cell disease are at risk of cognitive deficits and somatic growth delays beginning in early childhood. We examined growth velocity from age 2 years (height and body mass index progression over time) and cognitive functioning in 46 children with sickle cell disease 4 to 8 years of age. Height-for-age velocity was not associated with cognitive outcomes. Higher body mass index velocity was associated with higher scores on global cognitive and visual-motor abilities but not processing resources or academic achievement. Body mass index progression over time may be a clinically useful indicator of neurocognitive risk in sickle cell disease, as it may reflect multiple sickle cell disease-related risk factors.

Modulation of pain in pediatric sickle cell disease: understanding the balance between endothelin mediated vasoconstriction and apelin mediated vasodilation.

Children with sickle cell disease (SCD) have painful vaso-occlusive episodes (VOEs), which often reoccur across the individual's lifespan. Vaso-constrictive and vaso-dilatory molecules have been hypothesized to play a role in VOEs. Endothelin-1 (ET-1) is a potent vasoconstrictor that is released during VOEs and is correlated with pain history. Apelin is a vaso-dilatory peptide that also has a modulatory role in pain processing. We hypothesize that the ratio between vaso-dilatory and vaso-constrictive tone in children with SCD may be a marker of pain sensitization and vaso-occlusion. Plasma endothelin and apelin levels were measured in 47 children with SCD. Procedural pain and baseline pain were assessed via child- and caregiver-reports and observational distress. Pain history was assessed using retrospective chart review. Plasma apelin was related to age, with decreased levels in older children. The ratio between apelin and ET-1 was negatively correlated to observational baseline pain. The ratio between apelin and Big ET was negatively correlated to caregiver ratings of baseline pain and positively correlated to history of VOEs, which is possibly due to hydroxyurea treatment. These results suggest that an imbalance in the apelin and endothelin systems may contribute to an increasing number of VOEs and baseline pain in children with SCD.

Sensitization to acute procedural pain in pediatric sickle cell disease: modulation by painful vaso-occlusive episodes, age, and endothelin-1.

UNLABELLED: The impact of pain early in life is a salient issue for sickle cell disease (SCD), a genetic condition characterized by painful vaso-occlusive episodes (VOEs) that can begin in the first year of life and persist into adulthood. This study examined the effects of age and pain history (age of onset and frequency of recent VOEs) on acute procedural pain in children with SCD. Endothelin-1, a vaso-active peptide released during VOEs and acute tissue injury, and its precursor, Big Endothelin, were explored as markers of pain sensitization and vaso-occlusion. Sixty-one children with SCD (ages 2 to 18) underwent venipuncture at routine health visits. Procedural pain was assessed via child and caregiver reports and observational distress. Pain history was assessed using retrospective chart review. Three primary results were found: 1) younger age was associated with greater procedural pain across pain outcomes; 2) higher frequency of VOEs was associated with greater procedural pain based on observational distress (regardless of age); and 3) age was found to moderate the relationship between VOEs and procedural pain for child-reported pain and observational distress for children 5 years of age and older. Associations between the endothelin variables and pain prior to venipuncture were also observed. PERSPECTIVE: For children with SCD, the child's age and recent pain history should be considered in procedural pain management. The endothelin system may be involved in preprocedure pain, but additional research is needed to understand the role of endothelins in pain sensitization.

Relationships between somatic growth and cognitive functioning in young children with sickle cell disease.

OBJECTIVE: Children with sickle cell disease (SCD) exhibit poor somatic growth due to nutritional and metabolic effects, but potential relationships between growth and other areas of development are unclear. We examined whether growth is related to cognition and whether growth might be one marker of neurocognitive risk. METHODS: Sixty-four children with SCD and eighty-one demographically similar controls, ages 4 to 8 years, completed cognitive and anthropometric measures. RESULTS: Height-for-age partially accounted for cognitive decrements related to SCD on all cognitive measures. Higher body-mass-index was a significant predictor of higher visual-motor and academic achievement scores in children with SCD, but not in controls. CONCLUSIONS: In some children with SCD, especially those with HbSS and Hb Sbeta(0), low height-for-age may help to explain neurocognitive risk. Higher body-mass-index may be related to better cognitive outcomes in children with SCD. Nutrition deficits in SCD could explain the association between somatic growth and cognitive deficits.

Criterion and convergent validity for 4 measures of pain in a pediatric sickle cell disease population.

OBJECTIVE: To evaluate the psychometric properties of 4 measures of acute pain in youth with sickle cell disease (SCD) during a medical procedure. METHODS: Heart rate, child self-report, parent proxy-report, and observable pain behaviors were examined in 48 youth with SCD ages 2 to 17 years. Criterion validity for acute pain was assessed by responsiveness to a standardized painful stimulus (venipuncture) in a prospective pre-post design. Convergent validity was evaluated through the correlation across measures in reactivity to the stimulus. RESULTS: Child self-reported pain, parent proxy-report, and behavioral distress scores increased in response to venipuncture (concurrent and convergent validity). In contrast, heart rate did not reliably change in response to venipuncture. Extent of change in response to venipuncture showed moderate intercorrelation across child and parent pain ratings, and behavioral distress. Preprocedure pain ratings correlated with pain experienced during the procedure. An item analysis of observable pain behaviors suggested differences in the presentation of pain in SCD compared with previous pediatric research. CONCLUSIONS: Criterion and convergent validity were demonstrated for child-report, parent-report, and observable pain behaviors. These measures seem to tap into distinct, yet overlapping aspects of the pain experience. Assessment of acute procedural pain responses in SCD requires evaluation of preprocedural pain due to the frequent presence of low-level, baseline pain.

Use of handheld wireless technology for a home-based sickle cell pain management protocol.

PURPOSE: To evaluate use of a handheld electronic wireless device to implement a pain management protocol for participants with sickle cell disease (SCD). METHODS: Participants were 19 patients with SCD aged 9-20 who experienced vaso-occlusive pain. A single-session training on the use of cognitive-behavioral coping skills was followed by instruction on how to practice these skills and monitor daily pain experience using the device. Daily pain experience and practice of coping skills were collected for the 8-week intervention period using wireless technology. RESULTS: High rates of participation, daily diary completion and consumer satisfaction support the use of handheld wireless devices to implement this protocol. A comparison of the rates of self and device-recorded skills practice provides important information about the use of electronic monitoring for behavioral interventions. CONCLUSION: Wireless data transfer technology has significant potential to become a practical method to improve symptom monitoring and communication between patients and providers.