Search

Summary: Sickle cell anaemia (SCA) patients display elevated levels of circulating pro‐inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro‐inflammatory state in SCA remains unclear. This study aimed to characterize the whole‐blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty‐three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2‐min bouts of cycle ergometry interspersed with 1‐min rest intervals. Whole‐blood transcriptome profile (RNA‐seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up‐regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up‐ and 59 down‐regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL‐17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence‐based exercise prescription guidelines for this patient population. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) state level surveillance data are limited. We performed a retrospective review of emergency department (ED) visits and hospitalizations from individuals with SCD in Illinois (2016–2020) using the Illinois Health and Hospital Association's Comparative Health Care and Hospital Data Reporting Services. There were 48,094 outpatient ED visits and 31,686 hospitalizations. Most visits (67%) occurred in Cook County, were covered by public insurance (77%) and were from individuals with medium high (40.3%) or high (36.1%) poverty levels. SCD healthcare utilization remains high and surveillance data may inform SCD program development and resource allocation at the state level. Abbreviations CDC Centers for Disease Control and Prevention ED Emergency Department FDA Food & Drug Administration ICD International Classification of Diseases IL Illinois SCD Sickle cell disease [ABSTRACT FROM AUTHOR]

To determine the proportion of children with sickle cell disease (SCD) followed in a subspecialty clinic with access to a primary care provider (PCP) exhibiting practice-level qualities of a patient-centered medical home (PCMH). We surveyed 200 parents/guardians of children with SCD using a 44-item tool addressing PCP access, caregiver attitudes toward PCPs, barriers to healthcare utilization, perceived disease severity, and satisfaction with care received in the PCP versus SCD clinic settings. Individual PCMH criteria measured were a personal provider relationship and medical care characterized as accessible, comprehensive and coordinated. Although 94 % of respondents reported a PCP for their child, there was greater variation in the proportion of PCPs who met other individual PCMH criteria. A higher proportion of PCPs met criteria for coordinated care when compared to accessible or comprehensive care. In multivariate models, transportation availability, lower ER visit frequency and greater PCP visit frequency were associated favorably with having a PCP meeting criteria for accessible and coordinated care. Child and respondent demographics and disease severity had no impact on PCMH designation. Average respondent satisfaction scores for the SCD clinic was higher, when compared to satisfaction scores for the PCP. For children with SCD, access to a PCP is not synonymous with access to a medical home. While specific factors associated with PCMH access may be identified in children with SCD, their cause and effect relationships need further study. Keywords Sickle cell disease * Healthcare access * Primary care provider * Medical home, Introduction Recent national efforts have focused on increasing the proportion of children with access to a patient-centered medical home (PCMH), an ideal health delivery model that promotes continuous primary care [...]

Defects of the ankyrin-1 gene are the most common cause in humans of hereditary spherocytosis, an inherited anemia that affects patients of all ethnic groups. In some kindreds, linked-108/-153 nucleotide substitutions have been found in the upstream region of the ankyrin gene promoter that is active in erythroid cells. In vivo, the ankyrin erythroid promoter and its upstream region direct position-independent, uniform expression, a property of barrier insulators. Using human erythroid cell lines and primary cells and transgenic mice, here we have demonstrated that a region upstream of the erythroid promoter is a barrier insulator in vivo in erythroid cells. The region exhibited both functional and structural characteristics of a barrier, including prevention of gene silencing in an in vivo functional assay, appropriate chromatin configuration, and occupancy by barrier-associated proteins. Fragments with the -108/-153 spherocytosis-associated mutations failed to function as barrier insulators in vivo and demonstrated perturbations in barrier-associated chromatin configuration. In transgenic mice, flanking a mutant -108/-153 ankyrin gene promoter with the well-characterized chicken HS4 barrier insulator restored position-independent, uniform expression at levels comparable to wild-type. These data indicate that an upstream region of the ankyrin-1 erythroid promoter acts as a barrier insulator and identify disruption of the barrier element as a potential pathogenetic mechanism of human disease., Introduction The hereditary spherocytosis syndromes are a heterogeneous group of disorders characterized by anemia, intermittent jaundice, splenomegaly, and sphere-shaped (spherocytic) erythrocytes on peripheral blood smear (1). Hereditary spherocytosis affects patients [...]

Objective: We evaluated the safety of maximal cardiopulmonary exercise testing (CPET) in individuals with sickle cell disease (SCD). Maximal CPET using gas exchange analysis is the gold standard for measuring cardiopulmonary fitness in the laboratory, yet its safety in the SCD population is unclear.Design: Systematic review.Data Sources: Systematic search of Medline (PubMed), EMBASE, Cochrane, ClinicalTrials.gov and professional society websites for all published studies and abstracts through December 2020.Eligibility Criteria For Selecting Studies: Two reviewers independently extracted data of interest from studies that assessed safety outcomes of maximal CPET in children and adults with SCD. A modified version of the Newcastle-Ottawa Scale was used to assess for risk of bias in studies included.Results: In total, 24 studies met inclusion/exclusion criteria. Adverse events were reported separately or as part of study results in 36 (3.8%) of 939 participants with SCD undergoing maximal CPET in studies included. Most adverse events were related to transient ischaemic changes on ECG monitoring or oxygen desaturation during testing, which did not result in arrhythmias or other complications. Only 4 (0.43%) of 939 participants experienced pain events due to maximal CPET.Conclusion: Maximal CPET appears to be a safe testing modality in children and adults with SCD and can be used to better understand the physiological basis of reduced exercise capacity and guide exercise prescription in this population. Some studies did not focus on reporting adverse events related to exercise testing or failed to mention safety monitoring, which contributed to risk of bias. [ABSTRACT FROM AUTHOR]

Purpose: Sickle cell disease (SCD) significantly affects physical functioning. We examined physical activity (PA) patterns in children with SCD versus a national sample and factors associated with PA and participation in physical education and organized sports. Method: One hundred children with SCD completed a 58-item survey with questions from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) Physical Activity Questionnaire and others on physical education and sports, disease impact, and physical functioning. Results: Compared with NHANES participants, more children with SCD (67 vs 42%, p < .01) reported doing at least 10 min of moderate-to-vigorous intensity PA (MVPA)/week. Children with SCD also reported spending more days in MVPA (2.3 vs. 1.4 days/week, p < .01). However, fewer reported spending 60 min/day in either vigorous PA (VPA) (24 vs. 43%, p = .01) or MVPA (17 vs 23%, p < .01). In addition, 90% and 48% of children with SCD participated in physical education and sports, respectively. Greater disease impact on PA and physical functioning were associated with lower participation. Conclusion: Children with SCD are active at moderate to vigorous intensity for shorter durations. Negative personal beliefs about disease impact and poor physical functioning represent barriers to PA in SCD. [ABSTRACT FROM AUTHOR]

Summary: We examined heart rate variability (HRV) during exercise testing in 20 children with sickle cell anaemia (SCA) and 12 controls. Subjects achieved lower median HRV at peak exercise [standard deviation of R‐wave to R‐wave intervals (SDNN), 2·3 vs 2·9 ms, P = 0·027; logarithmic transformation of high frequency power (lnHF), 0·9 vs 1·3 ln(ms2), P = 0·047] and had lower post‐exercise HRV across minute‐by‐minute analysis of recovery. After adjustment for haemoglobin, fitness and SCA status, subjects had lower HRV at the end of recovery with differences increasing as baseline HRV increased. Further investigation of HRV and exercise safety in SCA is warranted. [ABSTRACT FROM AUTHOR]

Summary: We used near‐infrared spectroscopy to examine tissue oxygenation (StO2) during exercise in 17 children and young adults with sickle cell anaemia (SCA) and 13 controls. Patients had lower cerebral StO2 at all exercise stages and demonstrated significantly greater decreases in cerebral StO2 later during exercise. Quadriceps StO2 increased similarly in patients and controls during early exercise, but decreases from baseline were greater in patients during later exercise. At similar workloads, patients demonstrated lower cerebral StO2 (69·2 ± 6·6 vs. 79·5 ± 5·3%, P < 0·001) and trended towards lower quadriceps StO2 (67·7 ± 9·0 vs. 73·2 ± 7·9%, P = 0·09). Further studies of tissue oxygenation during exercise in SCA are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To determine the factors associated with exercise capacity in adults with sickle cell disease (SCD) and its relationship to hospitalizations and mortality. Methods: A total of 223 participants in the Cooperative Study of Sickle Cell Disease (CSSCD) (64% female, 70% hemoglobin SS/Sβ0 thalassemia, mean age 43.3 ± 7.5 years) underwent maximal exercise testing using a treadmill protocol with a mean duration of 11.6 ± 5.2 minutes. Results: Female sex (β = −3.34, 95% CI [−1.80, −4.88], P < 0.001), older age (β = −0.14, 95% CI [−0.24, −0.04], P = 0.005), higher body mass index (β = −0.23, 95% CI [−0.37, −0.10]; P = 0.001), and lower hemoglobin (β = 0.56, 95% CI [0.08, 1.04], P = 0.02) were independently associated with lower fitness, while there was a trend with abnormal pulmonary function testing (β = −1.42, 95% CI [−2.92, 0.07]; P = 0.06). Lower percent‐predicted forced expiratory volume in 1 second (FEV1) was independently associated with lower fitness (β = 0.08, 95% CI [0.03, 0.13], P = 0.001). Genotype and hospitalization rates for pain and acute chest syndrome (ACS) prior to testing were not associated with exercise capacity. Baseline exercise capacity predicted neither future pain or ACS nor survival in our cohort. Adults with SCD tolerated maximal exercise testing. Conclusions: Prospective studies are needed to further evaluate the impact of regular exercise and improved fitness on clinical outcomes and mortality in SCD. [ABSTRACT FROM AUTHOR]

Introduction: A growing population of adults living with severe, chronic childhood-onset health conditions has created a need for specialized health care delivered by providers who have expertise both in adult medicine and in those conditions. Optimal care of these patients requires systematic approaches to healthcare transition (HCT). Guidelines for HCT exist, but gaps in care occur, and there are limited data on outcomes of HCT processes. Methods: The Single Disease Workgroup of the Lifespan Domain Task Force of the National Center for Advancing Translational Sciences Clinical and Translational Science Award programs convened a group to review the current state of HCT and to identify gaps in research and practice. Using cystic fibrosis and sickle cell disease as models, key themes were developed. A literature search identified general and disease-specific articles. We summarized key findings. Results: We identified literature characterizing patient, parent and healthcare provider perspectives, recommendations for transition care, and barriers to effective transition. Conclusions: With increased survival of patients with severe childhood onset diseases, ongoing study of effective transition practices is essential as survival increases for severe childhood onset diseases. We propose pragmatic methods to enhance transition research to improve health and key outcomes. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) complications lead to poor health-related quality of life (HRQOL) and increased healthcare utilization in this population, which could be mitigated with hydroxyurea therapy; however, adherence is suboptimal. We assessed the relationship of healthcare utilization to hydroxyurea adherence and HRQOL amongst youth with SCD. Methods: Thirty-four patients with SCD (median age 14 years, IQR 12-18) on hydroxyurea participated in this cross-sectional study and completed Morisky Adherence Scale 8-items and Patient Reported Outcomes Measurement Information System (PROMIS®) HRQOL measures. A medical chart review was conducted to assess healthcare utilization. Results: Participants with more frequent hospitalizations and emergency room (ER) visits and longer length of stay (LOS) had significantly lower fetal hemoglobin (rs=-0.44; rs=-0.45; rs=-0.46, p < 0.05) and mean corpuscular volume (rs=-0.47; rs=-0.42; rs=-0.48, p < 0.05), respectively. More frequent hospitalizations and ER visits and longer LOS correlated significantly with worse fatigue (rs=0.51; rs=0.41; rs=0.53, p < 0.05), pain (rs=0.41; rs=0.38; rs=0.47, p < 0.05), physical function mobility (rs=-0.67; rs=-0.59; rs=-0.67, p < 0.05), depression (rs=0.38; rs=0.31; rs=0.42, p < 0.05), and social isolation (rs=0.76; rs=0.76; rs=-0.84, p < 0.05), respectively. Conclusions: We conclude that increased healthcare utilization in youth with SCD is associated with low adherence to hydroxyurea and worse HRQOL domain scores. It is important emphasize the clinical benefits of high adherence to hydroxyurea, particularly among youth with SCD. Future longitudinal studies are warranted to assess the directionality of these relationships, and may reveal modifiable behavioral factors associated with early changes in hydroxyurea adherence levels. [ABSTRACT FROM AUTHOR]