Journal of sickle cell disease最新文献

Objectives: Although SCD has traditionally been associated with underweight status, body mass index (BMI) status is shifting globally. As disease-modifying therapies have become available, BMI status has increased. Our aim was to determine the prevalence and risk factors of underweight, overweight, and obese statuses in SCD patients in low-middle and high-income countries.

Methods: The CASiRe research consortium cross-sectionally analyzed the association of BMI status (underweight, normal weight, overweight, and obesity) to age, genotype, treatment status, and associated clinical outcomes of 532 SCD patients from Italy, United States, and Ghana.

Results: Overall, BMI status varied significantly between countries (underweight P < .001, obesity P < .001, overweight P = .038). Underweight (9.5%-17.2%) and overweight/obesity (14%-27.8%) statuses increased from pediatrics to adults. Hemoglobin (Hgb) SC represented the highest percentage of overweight/obese patients (Hgb SC 49% vs SS/SB0Thal 16%, P < .001). Hydroxyurea use (HgbSS/SB0Thal [-]Hydroxyurea 11% vs [+]Hydroxyurea 32% overweight/obese, P < .001), higher hemoglobin levels (Adults, R = 0.396 P < .001), and genotype (HgbSS/SB0Thal vs SC, P < .001) correlated with overweight/obesity status. Lower hemoglobin (OR 0.77, P < .001) and male sex (OR 0.41 P < .001) were predictors of underweight status while higher hemoglobin (OR 1.38, P < .001) and older age (OR 1.01, P = .031) were predictors of obesity. Underweight status was associated with Ghanian site, male gender, leg ulcers, and microalbuminuria showing that it remains a significant clinical issue.

Conclusions: As access to disease-modifying therapy improves for SCD, monitoring for overweight and obesity and their comorbid conditions may be necessary. Underweight SCD patients should be carefully evaluated for end-organ complications, especially in low-resource settings.

Objective: Recruitment to clinical trials involving sickle cell disease (SCD) patients can be challenging, leaving trialists uncertain about how to optimize recruitment approaches and strategies. Informed by the Theoretical Domains Framework (TDF), we identified a comprehensive set of barriers and enablers to participation in SCD trials, and suggest how this theory-informed survey approach can improve trial recruitment strategies.

Methods: In collaboration with Clinical Trials Ontario and Sickle Cell Awareness Group of Ontario (SCAGO), we conducted a mixed methods study involving interviews with and surveys of SCD patients and families. We iteratively adapted a template survey based on think-aloud interviews, before administering the adapted survey online to SCAGO membership.

Results: Fifteen interviews with SCAGO members led to 49 survey items across 13 of 14 TDF domains. Four new items specific to the SCD community were added. Administration challenges led to low survey response, with only 22 people completing the survey. Eighteen items from 8 domains were seen as barriers (eg invasive tests/procedures, travel to study site). Twenty-two items from 9 domains were seen as enablers (eg hope for a cure, helping others).

Conclusion: Our theory-guided approach identified a comprehensive set of factors related to SCD trial participation, information that can support recruitment strategy development prior to trial onset. Low survey response rates precluded strong conclusions about the relative priority of the individual barriers and enablers; more work will be needed among a broader sample of SCD patients and families. Identification of theory-guided behavioral domains offers targeted suggestions for trial recruitment.

Objectives: SCD is associated with morbidity, mortality, and severe pain that is well modeled in humanized Berkeley SCD (HbSS) mice. Here, we conducted a comprehensive study to evaluate the effects of age on the development of the HbSS hyper-nociceptive phenotype. We also examined the antinociceptive effects of oxycodone, a commonly used analgesics to manage SCD-related pain, in both genotypes.

Methods: Mixed sex, 2-, 5-, and 10-month HbSS and HbAA control mice were assessed in cadre of stimulus-evoked and non-evoked functional assays. The dose-response relationship of oxycodone was evaluated in 10-month mice from both genotypes in a subset of in vivo assays. Finally, qRT-PCR was used to quantify the relative mRNA levels of opioid receptors and ligand precursors, and pro-inflammatory cytokines, from spinal cord and dorsal root ganglia.

Results: HbSS mice displayed augmented responses in stimulus-evoked assays and deficits in non-evoked functional behaviors that overall worsened in severity over age, compared with controls. Oxycodone dose-dependently attenuated mechanical hypersensitivity and produced thermal antinociception but failed to normalize (or worsened) functional behavior. Finally, HbSS mice exhibited overall or age-dependent differences in mRNA amounts of mu and kappa opioid receptors, POMC, IL-1β, and IL-6.

Conclusions: This study offers a comprehensive approach to investigate candidate drugs to treat SCD pain and explores biomarkers associated with the HbSS SCD mouse model. Although oxycodone ameliorated the hyper-nociceptive phenotype of HbSS mice, it failed to restore functional behavior, underscoring the need to identify novel therapeutic strategies that effectively reduce pain and restore functional behavior.

Background: Adults with sickle cell disease (SCD) often experience cognitive deficits and chronic pain, but the cerebral mechanisms underlying these symptoms remain unclear. Elevated cerebral blood flow (CBF) is a compensatory response to anemia, yet its impact on brain function and perception is not well understood.

Objective: To examine alterations in cerebral perfusion and resting-state brain function in adults with SCD and their associations with cognition and pain sensitivity.

Methods: Seven adults with SCD and 3 healthy controls underwent arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI). Metrics included global/regional CBF, resting-state functional connectivity (rsFC), and amplitude of low-frequency fluctuations (ALFF). Participants completed NIH Toolbox fluid cognition tests and the Pain Sensitivity Questionnaire (PSQ).

Results: SCD patients exhibited significantly higher global CBF (72.1 vs. 47.2 mL/100g/min; P = .04), reduced cortical zALFF (P = .0013), and elevated white-matter zALFF (P = .0023). They also showed resting-state network hyperconnectivity, with diminished anti-correlations between the default mode and salience networks. SCD participants scored lower on processing speed (P = .02) and reported higher pain sensitivity (PSQ total, P = .0040). Higher CBF was associated with slower cognitive performance but not directly with pain sensitivity. Exploratory mediation models suggested that altered brain activity may partially mediate this relationship.

Conclusions: Adults with SCD demonstrate cerebral hyperperfusion, disrupted functional connectivity, and altered spontaneous brain activity, which may contribute to cognitive slowing and heightened pain sensitivity. These findings highlight the need for further research into brain-targeted therapies in SCD.

Objectives: Palliative care (PC) is rare for patients with sickle cell disease (SCD). This study evaluated clinician attitudes toward PC for SCD.

Methods: A cross-sectional survey was conducted between October 2022 and February 2023. Clinicians were recruited from institutions across the United States.

Results: Eighty-six participants completed the survey. Most were physicians (90%), female (72%), had >10 years of experience (63%), and lacked prior PC training (57%). Most participants agreed (83%) that patients with SCD would benefit from PC, disagreed (99%) that PC is only for dying patients, and expressed interest (91%) in learning about PC interventions. Clinicians with prior PC training were more likely to agree that patients with SCD would benefit from PC (p = 0.016). Most participants thought patients referred to PC would worry about discussions on dying (76%), might feel abandoned (63%), might feel greater control (59%), and would feel cared for by their SCD provider (65%). Survey responses indicated that 41% and 63% of participants had never worked with PC in a collaborative care inpatient or outpatient setting, respectively.

Conclusion: Clinicians caring for patients with SCD recognize the potential benefits of PC, although they are unsure about patient responses to PC referrals. Collaborative care teams of SCD and PC specialists are rare. Educating clinicians and patients with SCD about PC is urgently needed to encourage greater collaboration among care teams, particularly in outpatient settings. Strengthened collaborations between SCD and PC specialists could enhance holistic support and quality of life for patients with SCD.

Introduction/objective: Lack of a well-characterized phenotype of High-Impact Chronic pain (HICP), that is, chronic pain (CP) with substantial restriction of participation in work, social, or self-care activities remains a critical gap in identifying individuals with CP and SCD at-risk for poor pain outcomes.

Methods: Retrospective study using the Electronic Health Record (EHR) at a large academic children's hospital.

Results: We report the clinical phenotype of 46 children with SCD diagnosed with HICP at time of consultation for Hematopoietic Cell Transplant (HCT). The mean age was 14.5 years (SD 3.9), 50% (n = 23) were female, 84.8% (n = 39) had HbSS genotype or similar, 30.4% (n = 14) had avascular necrosis, 84.8% (n = 39) were prescribed at least one disease modifying medication, and 41.3% (n = 19) were prescribed adjuvant analgesics. The cohort experienced a median of 6 (IQR 2, 9) and 8.50 (IQR 4.25, 15) episodes of healthcare utilization (HCU) for pain in 12 months and 24 months prior to the HCT consult, respectively, but about one-third did not experience frequent HCU (three or more episodes/year) for pain. In the 10 years leading up to the HCT consult, the incidence of HCU for pain year-over-year increased on an average by 15%. Clinical correlates of HICP from the EHR like prescription of adjuvant analgesics, cumulative doses of prescribed opioids, and diagnosis codes for CP were more likely to identify those who experienced frequent HCU for pain.

Conclusion: HICP in SCD is associated with substantial morbidity. This study underscores the importance of screening for HICP in SCD.

Objectives: Consensus Measures for Phenotypes and eXposures (PhenX) Toolkit (https://www.phenxtoolkit.org/) is a web-based catalog of recommended measurement protocols and associated bioinformatics tools to assist with study design and facilitate cross-study data integration and analyses. Before February 2023 (v.44), protocols specific to sickle cell disease did not address key psychosocial factors or social determinants of health that impact care and outcomes. This paper describes the protocol selection process and final recommendations to address this limitation.

Methods: To identify protocols for the new collection, the PhenX Sickle Cell Disease Research and Scientific Panel provided a list of scope elements for consideration and assembled a panel with relevant expertise in psychology, behavioral science, hematology, and nursing to form a Psychosocial and Social Determinants of Health Working Group. A consensus process prioritized and identified the scope elements and protocols. The 19 scope elements and related protocols initially selected were shared with the scientific community for public comment, informing final selections.

Results: The final 15 recommended protocols assess transition readiness, self-management, impact of early aging, stigma, trust in medical care and research, resilience, spirituality, and stress responses. Another 8 protocols were selected as supplemental information. Sickle cell-relevant social determinants of health protocols were also cross-listed from other PhenX Toolkit Collections.

Conclusion: Recommended protocols enhance the existing Sickle Cell Disease Research Collections and the individual and structural Social Determinants of Health Collections in the PhenX Toolkit. Furthermore, the protocols will promote using validated measurement tools to investigate psychosocial factors and social determinants in sickle cell disease.

Objectives: More individuals with SCD are living beyond initial life expectancy. Despite a growing population of older adults with SCD, little is known about their unique experiences and needs. Understanding the perspectives of older adults with SCD (age ≥ 50 years) could provide insight on the most pressing concerns that healthcare providers should focus on and strategies to promote healthy aging. The purpose of this study was to describe the aging experiences of older adults with SCD.

Methods: In this qualitative descriptive study, we conducted semi-structured interviews with 19 older adults with SCD who received care at a single comprehensive sickle cell program in the Southeastern United States. Data were analyzed using conventional content analysis.

Results: A total of 3 themes were identified. Theme 1 was "challenges with aging" with 2 subthemes: (a) internal challenges and (b) external challenges. Theme 2 was "wisdom gained with age for prevention and management of complications" with 2 subthemes: (a) lifestyle modifications and preventing complications and (b) managing sickle cell pain. Theme 3 was "living beyond life expectancy" with 2 subthemes: (a) differences in expectations for life expectancy and (b) factors contributing to longevity.

Conclusion: These perspectives from older adults with SCD provide guidance for healthcare providers on areas that are most important to them as they age. This also provides practical strategies for prevention and self-management of SCD complications that our participants reported contributed to their quality of life and longevity.

SCD is a family of genetic blood disorders that affects over 20 million people worldwide. SCD complications include pain, anemia, and early death. The hallmark cause of medical visits for people with SCD is pain, initially in the form of acute, severe, vaso-occlusive crises stemming from obstructed blood vessels and a plethora of underlying disordered biological mechanisms. Vaso-occlusive crises are unpredictable and are often associated with acute disability and/or hospitalization. Both vaso-occlusive crises and longer-term, chronic sickle cell pain can contribute to multi-system organ damage and eventually early death. Many of the disordered biological mechanisms of SCD, and how they relate to painful outcomes, are not well understood. Mathematical modeling can be a useful tool to study and analyze such disordered SCD biological phenomena: biodynamics, vaso-occlusion, and responses to SCD drug and gene therapy. In this review, we summarize the variety of mathematical modeling methods used to study SCD and provide specific examples of how mathematical modeling contributes new understandings of SCD.