Chronic pain is one of several debilitating complications that arises in patients suffering from sickle cell disease with many patients reporting concurrent sleep disturbance. It is widely recognized that pain disrupts sleep, however little is known about how sleep affects pain in this population. The current analyses examined SCD patients’ calculated Insomnia Severity Index (ISI) scores and its prospective relationship to self-reported clinical pain over a 90 day electronic diary period, 3 months of weekly telephone calls, and one year of monthly telephone calls. Seventy-two African American SCD patients rated their average daily clinical pain (x=26.60/100, SD=20.84) and 64 of them remained in the study and completed the weekly and monthly calls (average clinical pain x=2.5/10, SD=1.7 and x=3.5/10, SD=1.9, respectively). Multivariate models predicting clinical pain at each time period controlled for education, sex, age, central sensitization (CS), depression, and chronic opioid therapy (COT). ISI independently predicted 7.5 % of the variance in clinical pain during the diary period. The overall model accounted for 76% of the total variance, with COT, CS, and ISI significant covariates in the model. ISI independently predicted 7.6% of the variance in clinical pain over the 3 months of weekly calls. Both COT and ISI were significant in this model, for which 65% of the total variance was accounted. Lastly, in the twelve month period of monthly calls, ISI independently predicted 9.2% of the variance in clinical pain during the final 12 months of observation, accounting for 66% of the variance. COT, ISI, and depression were significant for this final model. These data suggest that sleep has a significant and long-lasting influence on SCD pain and deserves further, in-depth investigation. Abstract source

Stigma research is limited among youth with sickle cell disease (SCD). There is support for health-related stigma among adults with SCD. Part of the challenge of stigma research in youth with SCD is the limited availability of assessment tools to evaluate this construct. The purpose of the current study is to evaluate face validity among youth with SCD of the Sickle Cell Disease Health Related Stigma Scale (SCD-HRSS), which has been validated among young adults with SCD. Feedback from adolescents and young adults with SCD will inform modifications to the SCD-HRSS for youth. The SCD-HRSS is a 30-item questionnaire evaluating perception of stigma among the three existing domains: general public, physicians and family members. An additional 10 items were included to develop a nurse domain. 12 youth with SCD (M = 18.77, SD = 2.27) were recruited from both inpatient and outpatient settings. The participants were asked to rate each of the 40 SCD-HRSS items on a 5-point Likert scale regarding level of importance to their illness experience. Our findings suggest that 90.05% of items demonstrate consistent face validity, with four items identified as having inconsistent importance across two subscales: family (N =3) and nurses (N = 1). Of note, there were no problematic items identified within the general public and physician subscales. Overall, SCD-HRSS demonstrates face validity for a majority of items. The ability to understand the role of stigma for youth with SCD is dependent on the ability to reliably and accurately measure stigma. Face validity is the first step in the validation process. Future research implications include the further establishment of psychometric properties for the SCD-HRSS. Abstract source

Chronic opioid therapy is a common treatment regimen for patients with sickle cell disease (SCD), a chronically painful recessive hemoglobinopathy. The collective risk profile of chronic opioid therapy necessitates an understanding of which pain-related factors, such as affect and pain catastrophizing, are associated with the ebbs and flows of opioid use in daily life, a topic that has received very little attention among patients with any type of chronically painful condition, including SCD. We therefore investigated the variability of day-to-day patterns of short and long-acting opioid use and their associations with pain and pain-related cognitive and affective processes in daily life among patients with SCD using a nightly electronic diary (N = 45). Opioid use was self-reported and converted into oral morphine equivalents for analysis, which was conducted with mixed effects modeling. Results indicated that greater pain and pain catastrophizing were associated with greater use of short- acting opioids, and negative affect was associated with greater use of long-acting opioids. Additionally, the association of pain and short-acting opioid use was moderated by pain catastrophizing, showing that opioid use was elevated when patients catastrophized about their pain, even if they reported low levels of pain. These findings suggest that monitoring pain-related cognitive and affective variables may be a useful approach to understanding risk for problematic opioid use in patients with daily pain. Abstract source Full text

IMPORTANCE: Acute chest syndrome (ACS) is a common, serious complication of sickle cell disease (SCD) and a leading cause of hospitalization and death in both children and adults with SCD. Little is known about the effectiveness of guideline-recommended antibiotic regimens for the care of children hospitalized with ACS. OBJECTIVES: To use a large, national database to describe patterns of antibiotic use for children with SCD hospitalized for ACS and to determine whether receipt of guideline-adherent antibiotics was associated with lower readmission rates. RESULTS: Of the 14 480 hospitalizations, 6562 (45.3%) were in girls; median (interquartile range) age was 9 (4-14) years. Guideline-adherent antibiotics were provided in 10 654 of 14 480 hospitalizations for ACS (73.6%). Hospitalizations were most likely to include guideline-adherent antibiotics for children aged 5 to 9 years (3230 of 4047 [79.8%]) and declined to the lowest level for children 19 to 22 years (697 of 1088 [64.1%]). Between-hospital variation in antibiotic regimens was wide, with use of guideline-adherent antibiotics ranging from 24% to 90%. Children treated with guideline-adherent antibiotics had lower 30-day ACS-related (odds ratio [OR], 0.71; 95% CI, 0.50-1.00) and all-cause (OR, 0.50; 95% CI, 0.39-0.64) readmission rates vs children who received other regimens (cephalosporin and macrolide vs neither drug class). Abstract source Full text

PURPOSE: Opioid analgesics are commonly used to treat vaso-occlusive pain episodes in sickle cell disease (SCD), but comprehensive evidence characterizing opioid use in this patient population is limited. Our objective was to characterize opioid use patterns among SCD patients using a large nationwide database. METHODS: A large, US medical claims database was utilized to identify a cohort of 3882 SCD patients, and characteristics of opioid use were analyzed. Clinical variables including age, gender, medication use, health care utilization, and medical history were evaluated for correlations with opioid use. RESULTS: Forty percent of patients took opioid medications during a 12-month span, and the prevalence of any opioid use was highest for 20 to 29-year-old patients (58%). The median daily opioid dose was 1.85 mg (interquartile range: 0.62-10.68 mg) oral morphine equivalents (OME). While most opioid users took between 0 and 5 mg OME daily, 3% of pediatric patients and 23% of adult patients used more than 30-mg OME daily. High-dose opioid use was associated with older age, hydroxyurea therapy, nonsteroidal anti-inflammatory drug (NSAID) use, and frequent inpatient hospitalizations. In multivariable-adjusted analyses, patients with vaso-occlusive complications such as pain crisis (OR = 3.8, 95% CI 2.7-5.3) and avascular necrosis (AVN) (OR = 3.7, 95% CI 2.7-5.1) were associated with high-dose opioid use. CONCLUSIONS: Our study showed that only 40% SCD patients were on opioid analgesics during a 12-month span. However, a non-trivial number of patients used a much higher dose of opioids despite a relatively low average daily opioid dose among SCD patients, particularly with vaso-occlusive complications. Abstract source Full text

After nearly 20 years without new treatments for sickle cell disease, the FDA has approved L-glutamine oral powder to reduce severe complications of the blood disorder in patients aged 5 years or older. It also is the first sickle cell disease treatment approved for pediatric patients. Marketed as Endari, L-glutamine is an amino acid that can help prevent sickle red blood cells from sticking to the endothelial cells of blood vessels, which causes vaso-occlusion that results in severe pain and organ damage. Previously, the antimetabolite hydroxyurea had been the only FDA-approved drug for sickle cell disease. Abstract source Full text

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence but all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome. No significant effect of any of the treatments was seen compared to placebo. Immediate side effects were not found to be significantly different from placebo in the two trials where this information was reported. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers. Abstract source Full text

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients. Abstract source Full text

BACKGROUND: Persons with sickle cell disease (SCD) experience multiple medical and physical complications; the disease also has numerous effects on their social and emotional well-being. We hypothesized that adults with SCD in Jamaica experience moderate levels of stigma and illness uncertainty and that these experiences may be associated with socio-demographic factors, such as gender, educational status and economic status. METHODS: We surveyed 101 adults with SCD (54.5% female; mean age 31.6 ± 10.4 years; 72.2% homozygous SCD) using the Stigma in Sickle Cell Disease Scale (Adult), Mishel Uncertainty in Illness Scale (Adult) and a Socio-Demographic questionnaire. RESULTS: The mean stigma score was 33.6 ± 21.6 (range: 2-91) with no significant difference between males and females (32.3 ± 21.3 vs. 34.7 ± 21.9; p-value = 0.58). Illness uncertainty was greater in females than in males, though not statistically significant, (88.7 ± 13.5 vs. 82.6 ± 19.2; p-value: 0.07). Stigma and uncertainty had a significant positive correlation (r: 0.31; p-value: 0.01). In an age and sex controlled model, stigma scores were lower with higher numbers of household items (coef: -2.26; p-value: 0.001) and higher in those living in greater crowding (coef: 7.89; p-value: 0.002). Illness uncertainty was higher in females (coef: 6.94; p-value: 0.02) and lower with tertiary as compared with primary education (coef: -16.68; p-value: 0.03). CONCLUSION: The study highlights socioeconomic factors to be significant to the stigma and illness uncertainty experiences in SCD. Efforts by healthcare workers to reduce patient illness uncertainty may have additional impact, reducing their stigma. Abstract source Full text

Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider. While previous research has focused on the patient perspective of treatment-related decision making, there is a paucity of research investigating the physician perspective of treatment-related decision making. We conducted a qualitative study with physicians who were experts in the field of SCD. Interviews focused on physician perceptions of patient decisional needs as well as physicians' approach to decision making regarding disease-modifying therapies in SCD. Thirty-six physician interviews were analyzed, with a focus on their perspectives regarding available treatment options and on how they approach decision making with patients. We identified two narrative approaches. The Collaborative approach (CA) was characterized by emphasizing the need to discuss all possible treatment options to ensure that the patient and/or family was equipped to make an informed decision. The Proponent approach (PA) was characterized by strongly advocating a pre-determined treatment plan and providing patients/families with information, with the objective of convincing them to accept the treatment. An interplay of patient-related and disease-related factors, decision type and physician-related factors, as well as institutional frameworks, influenced physician perspectives on treatment options and decision making regarding these therapies. These findings point to the potential value of developing systems to foster patient engagement as a way of facilitating shared decision making. Abstract source Full text Full text (PMC)