Preschool Pain Management Program for Young Children with Sickle Cell Disease: A Pre-Post Feasibility Study.

OBJECTIVE: Vaso-occlusive pain crises in sickle cell disease (SCD) often begin in early childhood. We developed an online pain management intervention to teach caregivers of preschool-aged children with SCD behavioral pain management strategies. The feasibility study goals were to examine response to recruitment, barriers to participation, engagement, acceptability and perceived usefulness of the intervention, and suitability of outcome measures. METHODS: Caregivers of children aged 2.0-5.9 years with access to text messaging and a device to access online videos were recruited from a Southeastern outpatient hematology clinic for a 12-week intervention consisting of pain management videos. Videos taught caregivers behavioral pain management strategies and adaptive responses to pain. Workbook activities helped tailor strategies to their child. Caregivers completed process measures as well as baseline and follow-up measures of pain catastrophizing (Pain Catastrophizing Scale-Parent Report) and responses to their child's pain (Adult Response to Children's Symptoms). RESULTS: Fifty percent (10 of 20) of eligible parents enrolled. Caregivers partially completed (N = 6), completed (N = 3), or did not engage (N = 1) in the intervention. Caregivers who engaged in the program reported implementing the pain management strategies. The intervention was rated as high quality, relevant, and useful. Measures of pain catastrophizing and responses to their child's pain appeared sensitive to change. CONCLUSIONS: The intervention to promote adaptive coping to pain was acceptable and feasible for caregivers though we found barriers to delivering the intervention to parents. Evaluation of a modified version of the program is indicated to assess implementation issues and effectiveness.

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.

Changes in the developmental status of preschoolers with sickle cell disease.

Developmental monitoring and screening are recommended strategies for identifying children with sickle cell disease at high risk for cerebrovascular complications. Studies examining developmental screenings have provided little data on change over time. We examined screenings longitudinally in 43 children screened as two-year-olds and four-year-olds using the Ages and Stages Questionnaire, 2nd edition. Only two-thirds of children had stable screening outcomes. A new onset of cerebrovascular complications predicted the emergence of developmental delay (P = 0.017). Multivariate analysis suggested a benefit from formal developmental interventions. Regular developmental screening during the preschool period is important to identify systematic changes in developmental status.

Sociodemographic and Biomedical Correlates of Developmental Delay in 2- and 4-Year-Olds with Sickle Cell Disease.

BACKGROUND: Developmental delay occurs frequently in sickle cell disease (SCD). Psychosocial and biomedical factors contribute to delays, but most studies have not examined the timing of risk factors and developmental delay. We examined sociodemographic and biomedical factors to evaluate whether risks of developmental delay differed across 2 developmental periods. METHODS: We examined Ages and Stages Questionnaire, second edition (ASQ-2), outcomes in 2-year-olds (n = 100) and 4-year-olds (n = 101) with SCD. ASQ-2 data were obtained from routine developmental screenings administered as part of health care between 2009 and 2016 at a single hematology clinic. Medical record reviews were used to identify sociodemographic and biomedical factors associated with positive screenings for developmental delay. RESULTS: Two-year-olds with positive ASQ-2 screenings (n = 32; 32%) were less likely to have private health insurance or to have been in formal daycare and more likely to have a severe SCD genotype. Four-year-olds with positive screenings (n = 40; 40%) were more likely to have a severe SCD genotype or an abnormal transcranial Doppler ultrasound (TCD) examination indicating high stroke risk. The strength of the association between positive screenings and insurance status, severe genotypes, and TCD examinations differed across the 2 age groups. Domain-level outcomes on the ASQ-2 also differed across the 2 age groups. CONCLUSION: The cross-sectional data indicate biomedical and psychosocial risks are related to developmental delay, but the association with specific risk factors differs across age.

Neurodevelopmental Outcomes in Preterm Children with Sickle Cell Disease.

OBJECTIVES: To explore the combined effect of pediatric sickle cell disease (SCD) and preterm birth on cognitive functioning. METHODS: Cognitive functioning was examined in children ages 6-8 with high risk SCD genotypes born preterm (n = 20) and full-term (n = 59) and lower risk SCD genotypes/no SCD born preterm (n = 11) and full-term (n = 99) using tests previously shown to be sensitive to SCD-related neurocognitive deficits. Factorial ANOVAs and log linear analyses were conducted to examine the relationship between SCD risk, preterm birth status, and cognitive outcomes. Continuous scores were examined for specific tests. Children were categorized as having an abnormal screening outcome if at least one cognitive score was ≥1.5 standard deviations below the population mean. RESULTS: Children with elevated risk due to high risk SCD and preterm birth performed worse than other groups on a test of expressive language but not on tests that emphasize processing speed and working memory. There was a three-way interaction between preterm status, SCD risk, and abnormal screening outcome, which was largely driven by the increased likelihood of abnormal cognitive scores for children with high risk SCD born preterm. CONCLUSIONS: The combination of SCD and preterm birth may confer increased risk for language deficits and elevated rates of abnormal cognitive screenings. This suggests that neurodevelopmental risk imparted by comorbid SCD and preterm birth may manifest as heterogenous, rather than specific, patterns of cognitive deficits. Future studies are needed to clarify the domains of cognitive functioning most susceptible to disease-related effects of comorbid SCD and preterm birth.

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.

[Formula: see text] Social-environmental moderators of neurodevelopmental outcomes in youth born preterm: A systematic review.

Objective: Preterm birth represents a significant medical event that places infants at a markedly greater risk for neurodevelopmental problems and delays. Although the impact of medical factors on neurodevelopment for those born preterm has been thoroughly explored, less is known about how social-environmental factors (e.g., socioeconomic status, family functioning) moderate outcomes. This review explores the quantity and methodological rigor of research on social-environmental factors as moderators of the relationship between preterm birth and neurodevelopmental outcomes.Methods: Articles published between January 1980 and December 2016 were identified from a comprehensive meta-analysis and systematic review on neurodevelopmental outcomes following preterm birth. A systematic review of MEDLINE was conducted to identify articles published from January 2017 through April 2019.Results: Eighty articles met the inclusion criteria. The majority of studies matched preterm and control groups on social-environmental factors (n = 49). The remaining studies included social-environmental factors as moderators (n = 13) or correlates (n = 11) of neurodevelopmental outcomes. Only seven studies did not include reports on social-environmental factors.Conclusions: This systematic review suggests that social-environmental factors are often considered to be ancillary risk factors to the larger medical risk imparted by prematurity. Studies typically focused on socioeconomic status rather than more modifiable parent/family factors that can be targeted through intervention (e.g., parental mental health) and evidenced mixed findings regarding the significance of social-environmental factors as moderators. Further research is needed to identify the relative influence of social-environmental factors to inform future psychosocial interventions.

Leveraging the Mammography Setting to Raise Awareness and Facilitate Referral to Lung Cancer Screening: A Qualitative Analysis.

PURPOSE: Despite compelling support for the benefits of low-dose CT (LDCT) screening for lung cancer among high-risk individuals, awareness of LDCT screening and uptake remain low. The aim of this project was to explore the perspectives of ACR mammography screening program directors (MPDs) regarding efforts to raise LDCT screening awareness and appropriate referrals by identifying high-risk individuals participating in routine mammography. METHODS: MPDs were recruited from ACR-accredited mammography facilities to participate in semistructured interviews after the completion of an online survey. Interviews were conducted over the telephone, recorded, transcribed, and subsequently reviewed for accuracy. Twenty MPDs were interviewed, and 18 interviews were transcribed and included in the thematic analysis. A theme codebook was developed, and all interviews were coded using NVivo by two trained reviewers. RESULTS: Key themes were organized into four broad domains: (1) general attitudes toward the integration of LDCT screening, (2) identifying mammography patients at high risk for lung cancer, (3) counseling about LDCT screening, and (4) strategies to identify high-risk women and increase awareness and knowledge of LDCT screening. Overall, MPDs recognized the benefits of integrating mammography and LDCT screening and were receptive to educating and referring women for LDCT screening. However, training and workflow changes are needed to ensure successful implementation. CONCLUSIONS: Qualitative data suggest that MPDs are amenable to leveraging the mammography setting to engage women about LDCT screening; however, additional tools, training, and/or staffing may be necessary to leverage the full potential of reaching women at high risk for lung cancer within the context of mammographic screening.

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.

Does Obstructive Sleep Apnea Increase Cognitive Deficits in Pediatric Sickle Cell Disease?

OBJECTIVES: Although pediatric obstructive sleep apnea (OSA) is estimated to affect 2-3% of the general population, its prevalence in sickle cell disease (SCD) is much higher, with research suggesting a prevalence rate of upwards of 40%. Despite the similar underlying pathophysiological mechanisms of neurocognitive effects in pediatric OSA and SCD, there is a scarcity of information on how these two conditions interact. The aim of this study was to better understand the contribution of sleep apnea to neurocognitive deficits in children diagnosed with SCD. METHOD: This study assessed cognitive function in 26 children with comorbid SCD and OSA, 39 matched comparisons with SCD only, and 59 matched comparisons in children without a chronic health condition. RESULTS: There were significant differences on measures of processing speed and reading decoding, with children without a chronic health condition scoring better than both chronic health condition groups. Additionally, the no chronic health condition group performed better on a test of quantitative knowledge and reasoning and a test of visual-spatial construction than the SCD-only group. Contrary to our hypotheses, there were no between-group differences suggesting an additive impact of OSA on cognition. Exploratory analyses revealed associations within the group that had OSA showing that more severe OSA correlated with lower performance on measures of processing speed and quantitative knowledge/reasoning. CONCLUSIONS: Children with comorbid OSA and SCD do not present with greater deficits in cognitive functioning than children with SCD alone. However, severe OSA may confer additional risk for neurocognitive impairments.

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.

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.

Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

RATIONALE: Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. OBJECTIVES: The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. METHODS: Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. RESULTS: Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. CONCLUSIONS: These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

The effects of a shared history of drug exposure on social choice.

Selection theories of drug use propose that individuals choose or self-select into peer groups on the basis of perceived similarities with other group members with regard to their beliefs, attitudes, and histories of drug use. The purpose of the present study was to determine whether a shared history of drug exposure would influence choice of a social partner. Adolescent male rats were treated with either cocaine (3.0 mg/kg, intraperitoneally) or saline and their preference for a cocaine-treated rat or a saline-treated rat was measured in a partner preference test. Next, a series of conditioning trials were conducted in which rats were paired with a cocaine-treated and a saline-treated partner on alternating days for 10 days. Finally, a second partner preference test was conducted, in which preference for cocaine-treated and saline-treated partners was reassessed. Relative to baseline, rats showed an increase in the amount of time they spent with their similarly treated partner, and this effect was driven by cocaine-treated rats increasing the amount of time spent in proximity to their cocaine-treated partner after conditioning. These findings support a selection model of drug use by showing that a shared history of drug exposure is sufficient to establish a social preference for one individual over another.

Coping and posttraumatic growth in women with limb amputations.

While ample research has examined the psychological experiences of men with limb amputations, minimal research has examined the psychological experiences of women with limb amputations. The present study utilizes a qualitative design to examine coping and posttraumatic growth in women with limb amputations. Thirty women completed the posttraumatic growth inventory (PTGI) and provided open-ended responses about coping, social support, discrimination, support groups, and acceptance. Interpretative phenomenological analysis was used to discern emergent and superordinate themes in qualitative responses. Superordinate themes included social support (friendships/family and community), self-beliefs, resources, physical complications, spirituality, specific strategies, and acceptance. Concerns related specifically to participants' gender identity included appearance and motherhood. Overall, women reported moderate-to-high PTGI scores. The current findings address a void in the literature by illuminating the unique perspective of women with amputations. Future research should use quantitative methodology to expand on our research findings, as well as assess interventions to assist women adjusting to limb loss.