Objective: Hospital admissions are significant events in the care of individuals with sickle cell disease (SCD) due to associated costs and potential for quality of life compromise. Methods: This cross-sectional cohort study evaluated risk factors for admissions and readmissions between October 2014 and March 2016 in adults with SCD (n = 201) and caregivers of children with SCD (n = 330) at six centres across the U.S. Survey items assessed social determinants of health (e.g. educational attainment, difficulty paying bills), depressive symptoms, social support, health literacy, spirituality, missed clinic appointments, and outcomes hospital admissions and 30-day readmissions in the previous year. Results: A majority of adults (64%) and almost half of children (reported by caregivers: 43%) were admitted, and fewer readmitted (adults: 28%; children: 9%). The most common reason for hospitalization was uncontrolled pain (admission: adults: 84%, children: 69%; readmissions: adults: 83%, children: 69%). Children were less likely to have admissions/readmissions than adults (Admissions: OR: 0.35, 95% CI: [0.23,0.52]); Readmissions: 0.23 [0.13,0.41]). For all participants, missing appointments were associated with admissions (1.66 [1.07, 2.58]) and readmissions (2.68 [1.28, 6.29]), as were depressive symptoms (admissions: 1.36 [1.16,1.59]; readmissions: 1.24 [1.04, 1.49]). In adults, difficulty paying bills was associated with more admissions, (3.11 [1.47,6.62]) readmissions (3.7 [1.76,7.79]), and higher spirituality was associated with fewer readmissions (0.39 [0.18,0.81]). Discussion: Missing appointments was significantly associated with admissions and readmissions. Findings confirm that age, mental health, financial insecurity, spirituality, and clinic attendance are all modifiable factors that are associated with admissions and readmissions; addressing them could reduce hospitalizations. Abstract source

Sickle cell disease is a potentially debilitating hemoglobinopathy associated with early mortality. The only established curative therapy is hematopoietic cell transplantation (HCT) with a matched sibling donor. The National Institutes of Health nonmyeloablative regimen of alemtuzumab/300 cGy total body irradiation and prolonged sirolimus exposure for graft-versus-host disease (GVHD) prophylaxis was administered to 16 children and adolescents. Infused products were unmanipulated granulocyte colony stimulating factor mobilized peripheral blood stem cells. All patients achieved mixed donor-recipient engraftment with no cases of secondary graft failure to date. Two patients have donor myeloid chimerism in the range of 30% to 40%. No sickling crises post-HCT have been observed. Event-free and overall survival rates are 100% with median follow-up of 19.5 months. No cases of GVHD have been observed. Sirolimus weaning was possible in all but one eligible patient to date. Ongoing follow-up and a larger prospective clinical trial are required to determine the long-term safety and efficacy of this regimen in children. Abstract source

Introduction: Sickle cell disease (SCD) is an inherited disease with lifelong morbidity, whose complications include frequent acute painful vaso-occlusive episodes (VOEs) that often require hospitalization. The only pharmacotherapy currently in regular use for SCD management is hydroxyurea (hydroxycarbamide). Areas Covered: We review recent advances in pharmacotherapy for SCD and summarize promising synthetic agents that are in late-stage development (phase 3) for SCD. Expert Opinion: Emerging SCD therapies have been developed to target specific pathophysiological mechanisms of the disease, as either preventative or abortive approaches to VOEs. Continuous-use pharmacotherapeutics in late-phase development for VOE prevention include voxelotor (GBT440), which elevates hemoglobin oxygenation, and prasugrel, a platelet activation inhibitor. However, at least in the near future, it is probable that biological molecules will play a primary role in SCD preventative therapy; in combination with hydroxyurea, crizanlizumab, an anti-P-selectin monoclonal antibody, appears to reduce VOE frequency, while L-glutamine was the first substance licensed by the FDA for use in SCD in 20 years. Synthetic drugs, however, may represent key approaches for the management of individuals upon hospitalization for VOE, a major challenge for SCD. For example, rivipansel (GMI-1070), a pan-selectin inhibitor, has shown encouraging effects on hospitalization time and opioid use. Abstract source

The aim of this study was to evaluate the clinical, biological and genetic factors that could be associated with the use and dose of morphine during hospitalization for vaso-occlussive crisis (VOC) in adults with sickle cell disease. Ninety-nine hospitalizations for acute VOC (58 sickle cell disease patients aged 18 to 60 years, one to six hospitalizations each) were recorded; we investigated the associations between qualitative and quantitative opioid requirements and several biological, clinical, epidemiological and genetic parameters. Visual analog pain scale (VAS) was the only independent predictor of the qualitative need for morphine (mean value of 8.5 vs. 6.1 for the 77 hospitalizations that required morphine). A higher total administered morphine dose, which relates mainly to the overall crisis severity, was associated with a lower hemoglobin (Hb) level at entry. The mean daily morphine dose, which is more influenced by the individual sensitivity to morphine, was not influenced by the studied genetic parameters [sickle cell disease type, α-thalassemia (α-thal) status, UGT2B7 and ABCB1 genotypes] but a very slight negative association was found with the total bilirubin (BIL) level at entry. Our study demonstrated that physicians are often reluctant to prescribe morphine in sickle cell disease as a VAS of 6 corresponds to the usual threshold of administration in other instances. Total Hb at entry was also associated for the first time with higher total morphine consumption and could be used in a predictive VOC severity score. These results have to be confirmed and completed on larger cohorts. Abstract source

Conflicting evidence exists on the epidemiology of type 2 diabetes mellitus (T2DM) among patients with sickle cell disease (SCD). This study measured the prevalence, incidence and clinical outcomes associated with T2DM in a large US population of commercially-insured adults aged >=20 years with SCD between 2009 and 2014. Among 7070 patients with SCD, the mean age (median) was 39 (37) years and 60•8% were female. The standardized prevalence of T2DM among patients with SCD showed a modest increase, from 15•7% to 16•5% (P trend = 0•026), and was comparable to African-American respondents to the National Health and Nutrition Examination Survey (18•2%). Over 17 024 person-years, the crude incidence rate for T2DM was 25•4 per 1000 person-years. Incident T2DM was associated with comorbid hypertension (hazard ratio [HR] = 1•45, 95% confidence interval [CI] 1•14-1•83), and dyslipidaemia (HR = 1•43, 95%CI 1•04-1•96). Compared to SCD patients without T2DM, more SCD patients with T2DM had diagnoses of nephropathy (28•0% vs. 9•5%; P < 0•001), neuropathy (17•7% vs. 5•2%; P < 0•001) and stroke (24•1% vs. 9•2%; P < 0•001). Prevalence of T2DM in SCD patients is similar to the general African American population with an increasing trend in recent years. These trends support routine screening for T2DM in aging patients with SCD, especially those with comorbid hypertension and/or dyslipidaemia. Abstract source

Sickle cell disease (SCD) is associated with pain and decreased health-related quality of life (HRQOL). Coping strategies influence pain but have not been evaluated as mediating the relation between pain and HRQOL in pediatric SCD. The current study examined whether pain-related coping mediates the association between pain and HRQOL in children and adolescents with SCD. In total, 104 children and adolescents 8 to 18 years of age (Mage=12.93 y) with SCD attending outpatient clinics completed pain intensity, HRQOL, and pain-related coping measures. Multiple mediation analyses were used to examine whether pain-related coping mediated the pain and HRQOL relation and whether types of coping (ie, approach, emotion-focused avoidance, problem-focused avoidance) were independent mediators. Total indirect effects for models examining physical and psychosocial HRQOL were not significant. After controlling for covariates, emotion-focused avoidance significantly mediated the association between pain and physical HRQOL (effect: -0.023; bootstrapped SE: 0.018; 95% confidence interval: -0.0751, -0.0003) but not the pain and psychosocial HRQOL relation. Approach and problem-focused avoidance were not significant mediators. Coping with pain in pediatric SCD is an important avenue for clinical intervention and additional research. Among children with SCD reporting high pain intensity, interventions should emphasize negative impacts of emotion-focused avoidance coping and integrate other empirically supported coping strategies to improve HRQOL. Abstract source

Introduction: Sickle cell disease (SCD) is an inherited, multi-system, chronic disease with the highest prevalence affecting people of Sub-Saharan African descent. While major advances in SCD care have occurred over the last few decades in many African countries these advances are not readily available. Prior literature from Ghana and Kenya describe stigma, despair, and economic burden as well as hope when a child has SCD. When people migrate to North America with a child with SCD it is unknown whether their perception of the disease changes. We asked, "How do immigrant parents of children with SCD from Sub-Saharan Africa perceive, and manage the disease in the context of western medical care?" Methods: The research question was explored with qualitative methodology, specifically focused ethnography. Semi-structured interviews were conducted with parent(s). The interviews were audio recorded, transcribed, and open coded. Rigor was determined through methodological coherence, appropriate and sufficient sampling, and iterative data collection and analysis. Results: Twelve interviews were conducted. Identified themes are as follows: memories of SCD in Africa, the emotional journey towards acceptance, and parental approach to care for their child. Conclusions: Healthcare providers should be responsive to an immigrant families' needs and not expect linear progression of emotional acceptance to the diagnosis. Healthcare providers patience with the process helps establish trust, works to facilitate and encourage hope and acknowledges the strength of the families, and their dedication to their family member. Healthcare providers should acknowledge parents' sources of support (religion/family) and ensure parents are aware of medical advances. Abstract source

Background: With advances in disease-specific treatments and improved overall survival, obesity rates are rising among patients with sickle cell disease (SCD). The primary aim of this study was to evaluate the role of bariatric surgery on clinical outcomes among hospitalized obese patients with SCD. Methods: The United States Nationwide Inpatient Sample database was queried between 2004 and 2014 for discharges with co-diagnoses of morbid obesity and SCD. The primary outcome was in-hospital mortality. Secondary outcomes included vaso-occlusive crisis, acute chest syndrome, biliary-pancreatic complications, renal failure, urinary tract infection, malnutrition, sepsis, pneumonia, respiratory failure, thromboembolic events, strictures, wound infection, length of stay, and hospitalization costs. Using Poisson regression, adjusted incidence risk ratios (IRR) were derived for clinical outcomes in patients with prior-bariatric surgery compared to those without bariatric surgery. Results: Among 2549 patients with a discharge diagnosis of SCD and morbid obesity, only 42 patients (1.7%) had bariatric surgery. On multivariable analysis, bariatric surgery did not influence mortality (P = 0.98). Bariatric surgery was not associated with increased risk for acute chest syndrome, sepsis, multi-organ failure, biliary-pancreatic, or surgery-related complications (all P > 0.05). Interestingly, bariatric surgery decreased risk of vaso-occlusive crises (IRR 0.21; 95% CI, 0.07-0.69; P = 0.01) in these patients and was associated with a shorter length of stay (P < 0.001) but higher hospitalization costs (P < 0.001). Conclusions: Bariatric surgery may lower rates of vaso-occlusive crises in morbidly obese sickle cell patients without significantly affecting mortality and other adverse outcomes. In spite of this, these weight loss surgeries are underutilized in this select population. Abstract source

Pain is the leading cause of emergency department (ED) visits for individuals living with sickle cell disease (SCD). The care that is delivered in the ED is often cited by patients with SCD as the area of health care in greatest need of improvement. In 2014, the National Heart, Lung, and Blood Institute released guidelines for the care of SCD, including recommendations for the management of acute sickle cell pain in the ED. These guidelines provide a framework to understand the elements of ideal emergency sickle cell pain care; however, they do not provide guidance on barriers and facilitators to achieving these ideals in the complex system of the ED. Presented in this article are 4 tenets of implementing guideline-adherent emergency sickle cell care gleaned from the available literature and continuous quality improvement efforts at our institution. These include: (1) strategies to reduce negative provider attitudes toward patients with SCD; (2) strategies to reduce time-to-first-dose of analgesic medication; (3) strategies to improve ED pain care beyond the first dose of medication; and (4) strategies to improve ED patient safety. Application of the principles discussed within can improve patient and provider satisfaction, quality, and safety. Abstract source Full text

With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention. Abstract source Full text