Sleep disturbance, depression and pain in adults with sickle cell disease

Background Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease. Methods Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index and Beck Depression Inventory II screening measures as a cross-sectional survey. Scores greater than 5 (Pittsburgh Sleep Quality Index) and 16 (Beck Depression Inventory II) defined sleep disturbance and depression, respectively. Clinical and laboratory parameters were also assessed. Results The mean Pittsburgh Sleep Quality Index score was 8.4 (SD ± 4.2) indicating a 71.2% prevalence of sleep disturbance. The mean Beck Depression Inventory II score was 8.0 (SD ± 8.9). Sixty five (20.6%) participants had a score indicating depression, and half of these (10.0%) had thoughts of suicide. Both Pittsburgh Sleep Quality Index and Beck Depression Inventory II scores were significantly correlated (p \u3c .001). The number of days with mild/moderate pain (p = .001) and a history of headaches (p = .005) were independently associated with depression by multivariate regression analysis. Patients with sleep disturbance were older (p = .002), had higher body mass index (p = .011), had more days of pain (p = .003) and more frequent severe acute painful events (emergency room visits and hospitalizations) during the previous 12 months (p \u3c .001). Conclusions More than 70 percent of adults with sickle cell disease had sleep disturbance, while 21 percent showed evidence of clinical depression. Sleep disturbance and depression were correlated, and were most common among those with more frequent pain. Providers caring for adults with sickle cell disease and frequent pain should consider screening for these common co-morbidities. Additional study is needed to confirm these findings and to determine if treatments for pain, depression or sleep disturbances will improve quality of life measures in this patient population

Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

BackgroundAdults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea.ObjectivesWe retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.MethodsAn electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.ResultsThree hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, pConclusionsOur data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings

Central Sensitization Associated with Low Fetal Hemoglobin Levels in Adults with Sickle Cell Anemia.

Background and aims Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain. Methods We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls. Results Static thermal testing using cold stimuli showed lower pain thresholds (p = 0.04) and tolerance (p = 0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (p \u3c 0.0001) and change in scores with temporal summation at the heat pain threshold (p = 0.002). Similarly, with the use of pressure pain stimuli, sickle cell subjects reported higher pain ratings (p = 0.04), but not higher pressure pain tolerance/thresholds or allodynia to light tactile stimuli. Temporal summation pain score changes using 2 pinprick probes (256 and 512 mN) were significantly greater (p = 0.004 and p = 0.008) with sickle cell, and delayed recovery was associated with lower fetal hemoglobin (p = 0.002 and 0.003). Conclusions Exaggerated temporal summation responses provide evidence of central sensitization in SCA. Implications The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization

Characteristics at Enrollment and Survival Status Based On Hydroxyurea Status and Fetal Hemoglobin Quartiles in Patients with HbSS.

<p>^at-test</p><p>^bChi-square test</p><p>^cCox regression with age as the time-scale</p><p>^dWilcoxon rank-sum test</p><p>^N/ANot applicable</p><p>^eHydroxyurea doses >35 mg/kg/d are not FDA-approved for the general management of patients with sickle cell anemia and were usually used in patients in preparation for hematopoietic stem cell transplantation.</p><p>^fMean maximum HbF and MCV are defined as the mean calculation of the highest values observed for each subject.</p><p>*p<0.001 when comparing HbF Lower 25% to HbF Upper 25% groups</p><p>**p<0.0001 when comparing HbF Lower 25% to HbF Upper 25% groups</p><p>^#p<0.001 when comparing No Hydroxyurea to Any Hydroxyurea groups</p><p>^##p<0.0001 when comparing No Hydroxyurea to Any Hydroxyurea groups</p><p>Characteristics at Enrollment and Survival Status Based On Hydroxyurea Status and Fetal Hemoglobin Quartiles in Patients with HbSS.</p

Comparison of Hematologic and Organ Function Parameters at Enrollment and Last visits in Patients with HbSS Based on Hydroxyurea Status and Fetal Hemoglobin Quartile.

<p>Abbreviations: HU, hydroxyurea; Low HbF, maximum fetal hemoglobin within the lowest quartile; High HbF, maximum fetal hemoglobin within the highest quartile; ANC, absolute neutrophil count; MCV, mean corpuscular volume; ARC, absolute reticulocyte count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TRV, tricuspid regurgitant velocity; NT-ProBNP, brain natriuretic peptide</p><p>^aConversion factor from U/L to μkat/L is 0.017; conversion factor from mg/dL to μmoL/L is 17.1</p><p>^bWilcoxon rank-sum test, other p-values are from t-tests if not otherwise specified</p><p>^cEjection fraction and TRV were reported in 345 subjects at first visit and 261 subjects at last visit</p><p>^dNT-ProBNP levels are only reported in patients with a creatinine <1.0mg/dL, (N = 65 No HU, 165 any HU, 21 low HbF, 12 high HbF)</p><p>^#p<0.05 when comparing No Hydroxyurea to Any Hydroxyurea groups</p><p>^##p<0.001 when comparing No Hydroxyurea to Any Hydroxyurea groups</p><p>^###p<0.0001 when comparing No Hydroxyurea to Any Hydroxyurea groups</p><p>*p<0.05 when comparing HbF Lower 25% to HbF Upper 25% groups</p><p>**p<0.001 when comparing HbF Lower 25% to HbF Upper 25% groups</p><p>***p<0.0001 when comparing HbF Lower 25% to HbF Upper 25% groups</p><p>Comparison of Hematologic and Organ Function Parameters at Enrollment and Last visits in Patients with HbSS Based on Hydroxyurea Status and Fetal Hemoglobin Quartile.</p

Causes of Death in Patients with Homozygous Sickle Cell Disease.

<p>^aMore than one cause of death was assigned to 4 patients</p><p>^bOther: multi-organ failure (1); trauma (1); subglottic stenosis (1); acute myelogenous leukemia (1); hemolytic transfusion reaction (1); cocaine toxicity (1)</p><p>Causes of Death in Patients with Homozygous Sickle Cell Disease.</p

Cox Regression Analysis of Variables Associated with Survival for Subjects with HbSS.

<p>^aInput variables: age, hydroxyurea exposure, hydroxyurea dose, dose group, maximum fetal hemoglobin, hemoglobin, white blood cell count, alkaline phosphatase, total bilirubin, albumin, creatinine, ejection fraction, and tricuspid regurgitant velocity. The input variables were selected based on univariate analysis results if they were associated either with mortality or hydroxyurea use. The final model is shown in the table and is obtained through backward stepwise model selection and includes variables associated with hydroxyurea use if they were significant at the 0.10 level. The hazard ratio units represent increase per one unit change of the factor. Hydroxyurea dose groups are compared to no hydroxyurea.</p><p>Cox Regression Analysis of Variables Associated with Survival for Subjects with HbSS.</p