Sickle cell disease (SCD) is the single most important genetic cause of childhood mortality globally. Tanzania has one of the highest annual births of SCD individuals in the world, estimated to reach 11 000 births a year. Without intervention, 50-90% of children will die in childhood. However, cost-effective interventions have the potential to reduce childhood mortality by up to 70%. The effects of SCD are multi-dimensional, ranging from causing high morbidity and mortality, and reducing the quality of life, to imposing a high socio-economic burden on individuals, families and health systems. In the past 12 years, the SCD programme in Tanzania has developed, with local and global partnerships, a systematic framework for comprehensive research that is integrated into providing healthcare, training and advocacy in SCD. This report outlines the approach and achievements of collective initiatives for management and control of SCD in Tanzania. Abstract source Full text

OBJECTIVES: Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. METHODS: A convenience sample (N = 25, 18 women, mean age 38.5 ± 12.5 [20-58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. RESULTS: We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n = 15), peripheral sensitization (n = 1), a mix of central and peripheral sensitization (n = 8), or no sensitization (n = 1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. DISCUSSION: The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults. Abstract source Full text Full text (PMC)

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ(+)-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16-18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. Abstract source Full text Full text (PMC)

CONTEXT: Sickle cell disease (SCD) is a life-threatening condition that affects more than seven million people worldwide. The most common complication experienced by persons living with SCD is pain. Evidence supports the use of nonpharmacologic therapies in managing psychological and social complications of pain in persons with SCD, but there is little consensus if these approaches can also be applied for the treatment of pain in SCD. OBJECTIVES: To describe and synthesize the use of nonpharmacological therapies for reducing pain of any type and origin in persons with SCD. METHODS: A literature search was conducted using PsycINFO, PsycARTICLES, PubMed, CINAHL, and Embase. Databases were searched using the following terms: sickle cell, pain, and nonpharmacological therapies. Interventions were graded for methodological quality and categorized as 1) peer-support group therapies, 2) educational/psychological therapies, and 3) skill-based therapies. RESULTS: Twenty-eight nonpharmacological interventions for persons with SCD were examined. Of these studies, a wide variety of nonpharmacological interventions were tested. Twelve studies yielded significant improvements in pain, three studies reported no positive effect or differences between experimental and control conditions on pain or a pain-related outcome, and one study reported a negative or detrimental intervention effect. CONCLUSION: Approximately half of the studies reviewed demonstrated success in alleviating pain, suggesting that patients are able to use nonpharmacological interventions to reduce pain with some degree of success. Questions still remain regarding the efficacy and generalizability of these interventions for persons with SCD. Abstract source Full text Full text (PMC)

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation. Abstract source Full text

Interventions to assist reproductive health decision-making in populations affected by sickle cell disease (SCD) or trait (SCT) lack proven efficacy over time. Our aim was to compare effects of CHOICES, a Web-based multimedia education program on implementing informed reproductive plans, and usual care education (e-Book) on reproductive knowledge, intention, and behavior over 24 months. We randomized 234 participants with SCD (n = 138) or SCT (n = 96) (age 18-35 years, 35 % male, 94 % African American) to CHOICES and e-Book groups. Participants completed a sickle cell-specific reproductive measure before and four times after the intervention (6, 12, 18 and 24 months). Compared to the e-Book group the CHOICES group had significantly more improvement in knowledge over time (p = .004) but not intention (p = .18) or behavior (p = .69). At baseline, 114 (48.7 %) participants reported having partners who would not put the couple at risk for their children inheriting SCD. Of the 116 (49.6 %) at-risk participants, a higher poroportion of those who were in the CHOICES group chose partners that reduced their risk by the last visit than the e-Book group (p = .04). Study findings provide important insights for designing a national trial of the CHOICES intervention focusing on subjects whose partner status puts them at risk for having a child with SCD. Abstract source Full text Full text (PMC)

Documented deficiencies in adult sickle cell disease (SCD) care include poor access to knowledgeable providers and inadequate treatment in emergency departments (EDs).The aim of this study was to create patient-reported outcome measures of the quality of ambulatory and ED care for adults with SCD.We developed and pilot tested SCD quality of care questions consistent with Consumer Assessments of Healthcare Providers and Systems surveys. We applied psychometric methods to develop scores and evaluate reliability and validity.The participants of this study were adults with SCD (n = 556)-63% aged 18 to 34 years; 64% female; 64% SCD-SS-at 7 US sites.The measure used was Adult Sickle Cell Quality of Life Measurement information system Quality of Care survey.Most participants (90%) reported at least 1 severe pain episode (pain intensity 7.8 ± 2.3, 0-10 scale) in the past year. Most (81%) chose to manage pain at home rather than the ED, citing negative ED experiences (83%). Using factor analysis, we identified Access, Provider Interaction, and ED Care composites with reliable scores (Cronbach α 0.70-0.83) and construct validity (r = 0.32-0.83 correlations with global care ratings). Compared to general adult Consumer Assessments of Healthcare Providers and Systems scores, adults with SCD had worse care, adjusted for age, education, and general health.Results were consistent with other research reflecting deficiencies in ED care for adults with SCD. The Adult Sickle Cell Quality of Life Measurement Quality of Care measure is a useful self-report measure for documenting and tracking disparities in quality of SCD care. Abstract source Full text Full text (PMC)

Physiologic contributors to reduced exercise capacity in individuals with sickle cell anemia (SCA) are not well understood. The objective of this study was to characterize the cardiopulmonary response to maximal cardiopulmonary exercise testing (CPET) and determine factors associated with reduced exercise capacity among children and young adults with SCA. A cross-sectional cohort of 60 children and young adults (mean 15.1 ± 3.4 years) with hemoglobin SS or S/β(0) thalassemia and 30 matched controls (mean 14.6 ± 3.5 years) without SCA or sickle cell trait underwent maximal CPET by a graded, symptom-limited cycle ergometry protocol with breath-by-breath, gas exchange analysis. Compared to controls without SCA, subjects with SCA demonstrated significantly lower peak VO2 (26.9 ± 6.9 vs. 37.0 ± 9.2 mL/kg/min, P < 0.001). Subjects demonstrated slower oxygen uptake (ΔVO2/ΔWR, 9 ± 2 vs. 12 ± 2 mL/min/watt, P < 0.001) and lower oxygen pulse (ΔVO2/ΔHR, 12 ± 4 vs. 20 ± 7 mL/beat, P < 0.001) as well as reduced oxygen uptake efficiency (ΔVE/ΔVO2, 42 ± 8 vs. 32 ± 5, P < 0.001) and ventilation efficiency (ΔVE/ΔVCO2, 30.3 ± 3.7 vs. 27.3 ± 2.5, P < 0.001) during CPET. Peak VO2 remained significantly lower in subjects with SCA after adjusting for age, sex, body mass index (BMI), and hemoglobin, which were independent predictors of peak VO2 for subjects with SCA. In the largest study to date using maximal CPET in SCA, we demonstrate that children and young adults with SCA have reduced exercise capacity attributable to factors independent of anemia. Complex derangements in gas exchange and oxygen uptake during maximal exercise are common in this population. Abstract source Full text Full text (PMC)

Although recent studies show an improved survival of children with sickle cell disease in the US and Europe, for adult patients mortality remains high. This study was conducted to evaluate the factors associated with mortality in adult patients following the approval of hydroxyurea. We first evaluated the association between selected variables and mortality at an academic center (University of North Carolina). Data sources were then searched for publications from 1998 to June 2016, with meta-analysis of eligible studies conducted in North America and Europe to evaluate the associations of selected variables with mortality in adult patients. Nine studies, combined with the UNC cohort (total n=3257 patients) met the eligibility criteria. Mortality was significantly associated with age (per 10-year increase in age) [7 studies, 2306 participants; hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.10-1.50], tricuspid regurgitant jet velocity 2.5 m/s or more (5 studies, 1577 participants; HR: 3.03; 95%CI: 2.0-4.60), reticulocyte count (3 studies, 1050 participants; HR: 1.05; 95%CI: 1.01-1.10), log(N-terminal-pro-brain natriuretic peptide) (3 studies, 800 participants; HR: 1.68; 95%CI: 1.48-1.90), and fetal hemoglobin (7 studies, 2477 participants; HR: 0.97; 95%CI: 0.94-1.0). This study identifies variables associated with mortality in adult patients with sickle cell disease in the hydroxyurea era. Abstract source Full text Full text (PMC)

Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between WMHs and markers of endothelial dysfunction and CBF by quantifying WMH volume on 3.0 Tesla MRI. We included 40 children with HbSS or HbSβ(0) thalassaemia, with a mean age of 12.1 ± 2.6 years. Boys demonstrated an increased risk for WMHs (odds ratio 4.5, 95% confidence interval 1.2-17.4), unrelated to glucose-6-phosphate dehydrogenase deficiency. In patients with WMHs, lower fetal haemoglobin (HbF) was associated with a larger WMH volume (regression coefficient = -0.62, R2 = 0.5, P = 0.04). Lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower CBF in the white matter (regression coefficient = 0.07, R2 = 0.15, P = 0.03), suggesting that endothelial dysfunction could potentially hamper CBF. The findings of our explorative study suggest that a high level of HbF may be protective for WMHs and that endothelial dysfunction may contribute to the development of WMHs by reducing CBF. Abstract source Full text