Journal Article Annotations
2024, 3rd Quarter

Sickle cell

Annotations by Lauren Fields, MD and Elizabeth Prince, DO
October, 2024

Comorbid ADHD and Pediatric Sickle Cell Disease: Prevalence and Risk Factors.
Sleep Disruption Moderates the Daily Dynamics of Affect and Pain in Sickle Cell Disease.
Longitudinal neurocognitive effects of nonmyeloablative hematopoietic stem cell transplant among older adolescents and adults with sickle cell disease: A description and comparison with sibling donors.

PUBLICATION #1 — Sickle cell

Comorbid ADHD and Pediatric Sickle Cell Disease: Prevalence and Risk Factors.

Emily J Carlson, Nour Al Ghriwati, Pam Wolters, Mary Anne Tamula, John Tisdale, Courtney Fitzhugh, Matt Hsieh, Staci Martin.

Abstract: Neuropsychol Rehabil. 2024 Aug;34(7):899-918. doi: 10.1080/09602011.2023.2238948. Epub 2023 Aug 4.

Sickle cell disease (SCD) is a genetic blood condition that places youth at increased risk for deficits in complex attention suggestive of increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD). We used systematic screening to assess the prevalence of ADHD in a clinic-based sample of youth with SCD and explored factors related to ADHD. Caregivers of 107 children with SCD (ages 7-11 years) completed routine psychosocial screening which included inattentive symptoms of ADHD. Follow-up diagnostic procedures were completed for patients with elevated inattentive symptoms to assess for ADHD diagnoses. Biomedical and social-environmental variables were examined from the screening and medical records. Twenty-six percent of patients showed elevated inattentive symptoms with 13% meeting diagnostic criteria for ADHD diagnoses. Most children (75%) who met criteria for ADHD had not been previously diagnosed. Disease severity did not predict inattentive symptoms or ADHD diagnoses, though a measure of chronic inflammation was associated with ADHD. Family functioning was related to elevated inattentive symptoms but not ADHD diagnoses. Children with SCD show relatively high rates of ADHD with many cases not detected through routine care. Screening for ADHD as part of hematology care may be a feasible strategy to improve identification and access to intervention.

Annotation

The finding:
This observational, cross-sectional study screened a clinic-based sample of children with sickle cell disease (SCD) ages 7-11 and found that 26.2% of patients had elevated scores on screening for inattentive symptoms of ADHD. Subsequent diagnostic assessment of those participants who screened positive found an overall prevalence rate of 13.1% for ADHD inattentive- and combined-type (ADHD-I/C), or 15.9% including patients with a preexisting diagnosis based on chart review. Neither inattentive symptoms nor ADHD-I/C diagnoses were significantly associated with unmet social needs or common medical factors, however exploratory analysis identified a correlation with indices of chronic inflammation.

Strength and weaknesses:
Regarding the strengths of this study, rather than relying solely on screening and rating scales, the follow-up evaluations for participants in the study utilized more extensive diagnostic tools. Additional strengths include the consideration of socio-environmental and other medical factors that might be associated with neurodevelopmental outcomes. Limitations include that this was a single-site screening study, and therefore the findings may not be generalizable to other populations. Additionally, the use of inattentive symptoms for screening did not capture patients with only hyperactive symptoms of ADHD.

Relevance:
The prevalence of psychiatric diagnoses is not well characterized among individuals with SCD, and most studies rely primarily on screening tools. This study provides estimated prevalence rates of ADHD-I/C among children at a single site using more extensive diagnostic tools and provides a model for further evaluations of the prevalence of psychiatric conditions in individuals with SCD with the incorporation of socio-economic and other medical factors.

PUBLICATION #2 — Sickle cell

Sleep Disruption Moderates the Daily Dynamics of Affect and Pain in Sickle Cell Disease.

Ellis.

Abstract: J Pain Epub 2024 Jan 18.

Persons with sickle cell disease (SCD) often experience pain that can interfere with quality of life and daily activities. Pain can modulated by affect and sleep continuity; however, few studies have explored how these factors complementarily influence pain in adults with SCD. The study aims were to investigate 1) whether pain levels were heightened on days characterized by low positive affect and high negative affect, and 2) whether the relationship between affect and pain was intensified following nights of disrupted sleep. Adults with SCD (N = 25) completed ecological momentary assessments and daily sleep diaries. Mixed models were used to analyze the main and interactive effects of daily affect (positive affect and negative affect) and sleep disruption (wake after sleep onset and frequency of awakenings) on both daily average pain and daily maximum pain. Results suggested that daily average pain and maximum pain tended to be higher on days of low positive affect and high negative affect. Furthermore, the frequency of nocturnal awakenings moderated the relationship between positive affect and pain. On days where there were higher frequencies of nocturnal awakenings, low positive affect was associated with both average and maximum pain; however, this association was not observed with lower frequencies of nocturnal awakenings. The association between negative affect and maximum pain was also stronger at higher levels of awakenings. Results highlight the relevance of adjunctive interventions that target affect among populations with SCD and further suggest that sleep continuity may further facilitate these interventions, highlighting the importance of multimodal treatments. PERSPECTIVE: This study examined the effects of affect and sleep on pain among adults with sickle cell disease (SCD). Higher pain occurred on days of low positive affect and high negative affect, particularly following nights of more frequent awakenings. These findings emphasize the importance of addressing affect and sleep in SCD treatment.

Annotation

The finding:
Twenty-five adult participants were assessed using five daily ecological momentary assessments of affect, pain, and prescription opioid use as well as daily sleep diaries. Findings showed an inverse association between daily positive affect and same-day average and maximum pain and an association between higher daily negative affect and same-day average and maximum pain when controlling for quality of sleep. Days with increased nocturnal awakenings were associated with subsequent days of higher average pain. The frequency of nocturnal awakenings moderated the effect of positive affect on daily average pain, as well as the effect of both positive and negative affect on maximum daily pain.

Strength and weaknesses:
Strengths include a clear and replicable study design and the use of assessments via smartphone to facilitate the potential scalability of the study. Limitations include small sample size, reliance on participant self-report, and that individuals with more severe psychiatric illness and those with more severe sickle cell disease (SCD) were excluded from participation.

Relevance:
This study emphasizes the importance of understanding the multifactorial nature of pain phenomena in SCD. Assessing and targeting factors that are associated with worsened pain, such as sleep quality and affect, may help to improve the quality of life for patients with SCD.

PUBLICATION #3 — Sickle cell

Longitudinal neurocognitive effects of nonmyeloablative hematopoietic stem cell transplant among older adolescents and adults with sickle cell disease: A description and comparison with sibling donors.

Emily J Carlson, Nour Al Ghriwati, Pam Wolters, Mary Anne Tamula, John Tisdale, Courtney Fitzhugh, Matt Hsieh, Staci Martin.

Abstract: Neuropsychol Rehabil. 2024 Aug;34(7):899-918. doi: 10.1080/09602011.2023.2238948. Epub 2023 Aug 4.

Sickle cell disease (SCD) is associated with increased risk of neurocognitive deficits. However, whether functioning changes following nonmyeloablative hematopoietic stem cell transplant (HSCT) remains unclear. This study aimed to examine changes in neuropsychological functioning pre- to post-transplant among patients with SCD and compare patients and siblings. Adults with SCD (n = 47; M_age = 31.8 ± 8.9) and their sibling stem cell donors (n = 22; M_age = 30.5± 9.2) enrolled on a nonmyeloablative HCST protocol completed cognitive and patient-reported outcome assessments at baseline and 12 months post-transplant. Path analyses were used to assess associations between pre-transplant variables and sibling/patient group status and post-transplant function. Mean patient cognitive scores were average at both timepoints. Patient processing speed and somatic complaints improved from baseline to follow-up. Baseline performance predicted follow-up performance across cognitive variables; patient/sibling status predicted follow-up performance on some processing speed measures. Results suggest that patients with SCD demonstrate slower processing speed than siblings. Processing speed increased pre- to post-HSCT among patients and siblings, and on some measures patients demonstrated greater improvement. Thus, HSCT may improve processing speed in patients, although further confirmation is needed. Findings provide promising evidence that neurocognitive functioning remains stable without detrimental effects from pre- to 12-months post nonmyeloablative HSCT in individuals with SCD.

Annotation

The finding:
Twenty-two adults with sickle cell disease (SCD) and their sibling donors in a nonmyeloablative hematopoietic stem cell transplant (HSCT) protocol completed baseline and 12-month post-transplant cognitive testing. Patients with SCD had slower processing speed than siblings. Post-transplant, processing speeds improved more for patients than siblings.

Strength and weaknesses:
Matched testing with sibling donors is an elegant study design, but the sample size was small and may not be generalizable to all adults with SCD. There were likely practice effects that explain improvements in subsequent testing, limiting interpretations of observed improvements.

Relevance:
CL psychiatrists should be aware of the risk of cognitive deficits in adults with SCD as this may impact overall functioning, including engagement in the health care system. Furthermore, as more patients are exposed to transformative therapies, like HSCT and gene therapy, it is reassuring that HSCT does not appear to worsen cognitive functioning.