Abstract Animations for the Communication and Assessment of Pain in Adults: Cross-Sectional Feasibility Study.

BACKGROUND: Pain is the most common physical symptom requiring medical care, yet the current methods for assessing pain are sorely inadequate. Pain assessment tools can be either too simplistic or take too long to complete to be useful for point-of-care diagnosis and treatment. OBJECTIVE: The aim was to develop and test Painimation, a novel tool that uses graphic visualizations and animations instead of words or numeric scales to assess pain quality, intensity, and course. This study examines the utility of abstract animations as a measure of pain. METHODS: Painimation was evaluated in a chronic pain medicine clinic. Eligible patients were receiving treatment for pain and reported pain more days than not for at least 3 months. Using a tablet computer, participating patients completed the Painimation instrument, the McGill Pain Questionnaire (MPQ), and the PainDETECT questionnaire for neuropathic symptoms. RESULTS: Participants (N=170) completed Painimation and indicated it was useful for describing their pain (mean 4.1, SE 0.1 out of 5 on a usefulness scale), and 130 of 162 participants (80.2%) agreed or strongly agreed that they would use Painimation to communicate with their providers. Animations selected corresponded with pain adjectives endorsed on the MPQ. Further, selection of the electrifying animation was associated with self-reported neuropathic pain (r=.16, P=.03), similar to the association between neuropathic pain and PainDETECT (r=.17, P=.03). Painimation was associated with PainDETECT (r=.35, P<.001). CONCLUSIONS: Using animations may be a faster and more patient-centered method for assessing pain and is not limited by age, literacy level, or language; however, more data are needed to assess the validity of this approach. To establish the validity of using abstract animations ("painimations") for communicating and assessing pain, apps and other digital tools using painimations will need to be tested longitudinally across a larger pain population and also within specific, more homogenous pain conditions.

Factors associated with survival in a contemporary adult sickle cell disease cohort.

In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand the major contributors to early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who were enrolled since 2002 at three university hospitals in the southeast United States. Subjects were followed up for a median of 9.3 years. At enrollment, clinical parameters were collected, including hemoglobin (Hb) genotype, baseline laboratory values, comorbidities, and medication usage. Levels of soluble adhesion molecules were measured for a subset of 87 subjects. The relationship of clinical characteristics to survival was determined using regression analysis. Median age at enrollment was 32 years. Median survival was 61 years for all subjects. Median survival for Hb SS and Sß(0) was 58 years and for Hb SC and Sß(+) was 66 years. Elevated white blood count, lower estimated glomerular filtration rate, proteinuria, frequency of pain crises, pulmonary hypertension, cerebrovascular events, seizures, stroke, sVCAM-1, and short-acting narcotics use were significantly associated with decreased survival. Forty-two percent of subjects were on hydroxyurea therapy, which was not associated with survival. SCD continues to reduce life expectancy for affected individuals, particularly those with Hb Sß(0) and SS. Not only were comorbidities individually associated with decreased survival but also an additive effect was observed, thus, those with a greater number of negative endpoints had worse survival (P < 0.0001). The association of higher sVCAM-1 levels with decreased survival suggests that targeted therapies to reduce endothelial damage and inflammation may also be beneficial.

MYH9 and APOL1 are both associated with sickle cell disease nephropathy.

Renal failure occurs in 5-18% of sickle cell disease (SCD) patients and is associated with early mortality. At-risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The myosin, heavy chain 9, non-muscle (MYH9) and apolipoprotein L1 (APOL1) genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans. We genotyped 26 single nucleotide polymorphisms (SNPs) in MYH9 and 2 SNPs in APOL1 (representing the G1 and G2 tags) in 521 unrelated adult (18-83 years) SCD patients screened for proteinuria. Using logistic regression, SNPs were evaluated for association with proteinuria. Seven SNPs in MYH9 and one in APOL1 remained significantly associated with proteinuria after multiple testing correction (P < 0·0025). An MYH9 risk haplotype (P = 0·001) and the APOL1 G1/G2 recessive model (P < 0·0001) were strongly associated with proteinuria, even when accounting for the other. Glomerular filtration rate was negatively correlated with proteinuria (P < 0·0001), and was significantly predicted by an interaction between MYH9 and APOL1 in age-adjusted analyses. Our data provide insight into the pathobiology of renal dysfunction in SCD, suggesting that MYH9 and APOL1 are both associated with risk.

Living with sickle cell disease: traversing 'race' and identity.

OBJECTIVES: Sickle cell disease (SCD) has a distinctive social history that continues to influence research and clinical practice related to the disease. Despite the historical link between SCD and concepts of 'race', there is limited empirical information on the relationships among SCD patients' 'race'/ancestry/ethnicity/nationality, their beliefs and attitudes associated with these identities, and their SCD experiences and outcomes. We conducted a preliminary study to explore some of these relationships. DESIGN: This US-based study comprised 46 adults with SCD, 20 males and 26 females, with an average age of 32.04 (18-59) years. Using US Census 'race' categories, 42 participants identified themselves as 'Black or African American', two as 'Hispanic/Latino', and two as 'Other'. All participants completed a computer-based questionnaire that included measures of sociodemographics and 'racial' identity. Indicators of disease severity and frequency of hospitalizations were obtained from their medical records. Two open-ended questions explored the impact of SCD and 'race' on participants' experiences and another probed their understanding of the term 'race'. RESULTS: Overall, participants had positive regard for their 'race' and endorsed assimilation and humanist ideologies. 'Racial' identity was not related to disease severity or hospitalizations. Participants with non-US-born parents had higher levels of minority ideology than those with US-born parents (p<.01). Public regard beliefs were negatively associated with participants' perspective that SCD influenced how others perceived and treated them (r=-.35; p=.02). Centrality of 'race' and a nationalist ideology were positively associated with participants' belief that their 'race' influenced their experience with SCD (r=.31; p=.04 and r=.45; p=.001, respectively). The open-ended responses reveal that SCD and 'race' had varied effects on participants' experiences. CONCLUSION: This study illustrates the complexity of the interplay between 'racial' identity beliefs and patients' experiences with SCD, as well as the role of 'race' in these experiences. Implications of the findings are discussed.

Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease.

Sickle cell disease (SCD) is associated with early mortality. We sought to determine the incidence, cause, and risk factors for death in an adult population of patients with SCD. All patients aged >/=18 years seen at the Adult Sickle Cell Center at Duke University Medical Center between January 2000 and April 2005 were enrolled. Forty-three patients (21 males and 22 females) died during the study period. The median age of survival was 39 years for females (95% CI: 34-56), 40 years for males (95% CI: 34-48), and 40 years overall (95% CI: 35-48). Cardiac causes of death accounted for 25.6% (11/43 patients); pulmonary, 14.0% (six patients); other SCD related, 32.6% (14 patients); unknown, 14.0% (six patients); and others, 14.0% (six patients). Pulseless electrical activity arrest, pulmonary emboli, multiorgan failure, and stroke were the most frequent causes of death. Among the deceased patients, the most common premorbid conditions were cardiopulmonary: acute chest syndrome/pneumonia (58.1%), Pulmonary hypertension (pHTN; 41.9%), systemic HTN (25.6%), congestive heart failure (25.6%), myocardial infarction (20.9%), and arrhythmias (14.0%). Tricuspid regurgitant jet velocity was significantly higher (3.1 m/sec vs. 2.6 m/sec, P < 0.001) and hemoglobin significantly lower (8.3 g/dL vs. 9.2 g/dL, P < 0.05) in deceased patients when compared with patients who lived, respectively. With improved preventive and therapeutic advances, including hydroxyurea therapy, acute complications such as infection are no longer the leading cause of death; instead, causes of death and premorbid conditions are shifting to chronic cardiopulmonary complications. Further, arrhythmia leading to premature death is under-recognized in SCD and warrants further investigation.

Clinical and sociodemographic factors predict coping styles among adults with sickle cell disease.

UNLABELLED: Sickle cell disease (SCD) presents a significant physical and psychological burden for persons with this chronic disease; however, little is known about how individuals with SCD--adult patients in particular--cope with disease-related stressors. The aim of this study was to identify and characterize factors that may influence the styles of coping among adults with SCD. METHODS: The study sample included 46 adult patients with SCD-20 men and 26 women--with an average age of 32.04 years (range, 18-59). Patients completed a computer-based questionnaire that included measures of sociodemographics and the COPE, a measure of coping styles. End organ damage disease severity scores and frequency of hospitalizations were obtained from patients' medical records. RESULTS: Education was negatively associated with use of denial (r = -0.35; p = .017) and positively associated with use of planning (r = .29, p = .045). However, age, type of SCD, end organ damage, and frequency of hospitalizations were not associated with patient coping. There were significant gender differences in coping, with women reporting greater use of venting, positive reframing, and religion as coping strategies than men (all p < .05). Women also tended to use more planning, emotional support, and acceptance than men (all p < .10). These associations were not moderated by age, type of SCD, disease severity, or hospitalizations. Further, these gender differences were not better explained by differences in SCD experience. DISCUSSION: These findings suggest that in patients reporting similar experiences with SCD, coping differs by education and gender. Moreover, these differences in coping cannot be explained by clinical factors such as end organ damage and health care utilization. Sickle cell disease (SCD) presents a significant physical and psychological burden for persons with this chronic disease; however, little is known about how individuals with SCD--adult patients in particular--cope with disease-related stressors. The aim of this study was to identify and characterize factors that may influence the styles of coping among adults with SCD.

Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease.

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-derived 2)-like 2), an oxidative stress regulator. We found that activation of NRF2 with sulforaphane (SFN) in erythroid progenitors significantly increased the expression of NRF2 targets HMOX1, NQO1, and HBG1 (subunit of fetal hemoglobin) in a dose-dependent manner. Therefore, we hypothesized that NRF2 activation with SFN may offer therapeutic benefits for SCD patients by restoring oxidative capacity and increasing fetal hemoglobin concentration. To test this hypothesis, we performed a Phase 1, open-label, dose-escalation study of SFN, contained in a broccoli sprout homogenate (BSH) that naturally contains SFN, in adults with SCD. The primary and secondary study endpoints were safety and physiological response to NRF2 activation, respectively. We found that BSH was well tolerated, and the few adverse events that occurred during the trial were not likely related to BSH consumption. We observed an increase in the mean relative whole blood mRNA levels for the NRF2 target HMOX1 (p = 0.02) on the last day of BSH treatment, compared to pre-treatment. We also observed a trend toward increased mean relative mRNA levels of the NRF2 target HBG1 (p = 0.10) from baseline to end of treatment, but without significant changes in HbF protein. We conclude that BSH, in the provided doses, is safe in stable SCD patients and may induce changes in gene expression levels. We therefore propose investigation of more potent NRF2 inducers, which may elicit more robust physiological changes and offer clinical benefits to SCD patients. Trial registration: ClinicalTrials.gov NCT01715480.

Moderate chronic pain, weight and dietary intake in African-American adult patients with sickle cell disease.

In this exploratory study, we evaluated weight status and dietary intake patterns during painful episodes in adult patients with SCD. Specifically, we explored the relation between pain severity and body mass index (BMI), and we tested the hypothesis that dietary intake would be reduced and dietary content altered during periods of increased pain. We conducted an analysis of survey data from 62 patients involved in a longitudinal evaluation of the relationship of medical and psychosocial factors to pain. Nearly half of patients with SCD were overweight, and 20% were obese. BMI was positively related to interference associated with pain. Although BMI was not statistically associated with reported pain severity, >40% of patients reported that they perceived their pain to be affected by their weight. Less than 20% of patients reported that they perceived that their weight affected their pain. Regarding dietary patterns, the majority of patients reported eating less during episodes of pain and significantly decreasing their intake of fats and proteins. We conclude that there is a need to better understand the relation among weight, dietary patterns and pain in patients with SCD in order to provide patients with accurate education and effective treatment recommendations for managing their disease and reducing current and future risks of lifestyle and disease-related morbidities.

Effect of propranolol as antiadhesive therapy in sickle cell disease.

Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a ß-adrenergic receptor and protein kinase A-dependent manner. Studies in vitro as well as in vivo have suggested that adrenergic stimuli like epinephrine may contribute to vaso-occlusion associated with physiologic stress. We conducted both animal studies and a Phase I dose-escalation study in sickle cell disease (SCD) patients to investigate whether systemically administered propranolol inhibits SSRBC adhesion and to document the safety of propranolol in SCD. Systemically administered propranolol prevented SSRBC adhesion and associated vaso-occlusion in a mouse model. In patients receiving a single oral dose of 10, 20, or 40 mg propranolol, SSRBC adhesion to ECs was studied before and after propranolol, with and without stimulation with epinephrine. Propranolol administration significantly reduced epinephrine-stimulated SSRBC adhesion in a dose dependent manner (p = 0.03), with maximum inhibition achieved at 40 mg. Adverse events were not severe, did not show dose dependence, and were likely unrelated to drug. No significant heart rate changes occurred. These results imply that ß-blockers may have a role as antiadhesive therapy for SCD.

Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes.

Screening for pulmonary hypertension (pHTN) has not yet become routine in sickle cell disease (SCD), despite clinical evidence of its high prevalence and associated mortality. Our objectives are to identify clinical conditions and laboratory findings predictive of/or associated with pHTN. One hundred twenty-five adult outpatients with Hb SS, SC, SOArab, Sbeta(0), or Sbeta(+) thalassemia, who underwent echocardiography and/or right heart catheterization due to cardiorespiratory symptoms, were studied. pHTN was identified in 36% (28/77) of SS/Sbeta(0) and in 25% (12/48) of SC/SOArab/Sbeta(+) patients studied. In SS/Sbeta(0) patients, pHTN was associated with low hemoglobin, low GFR, increasing age, no history of treatment with hydroxyurea and a history of leg ulcers, with trends for associations with higher total bilirubin, LDH levels, systolic systemic blood pressure, history of avascular necrosis, seizures, and cerebrovascular events. Twelve (40%) of the SS/Sbeta(0) patients with pHTN had >or= 1+ proteinuria. (P<0.039). The presence of proteinuria correlated with lower GFR and had a high positive predictive value (0.60) for pHTN in subjects with SS/Sbeta(0). The data also provided evidence that pHTN in this population is associated with right heart failure, with echocardiographic evidence of right ventricle enlargement and pericardial effusion. This study confirmed that even relatively mild elevations in pulmonary pressure are associated with high prospective mortality (hazard ratio: 15.9). We concluded that pHTN has a high prevalence in all Hb S related syndromes and is associated with increased mortality in SS/Sbeta(0). Kidney dysfunction, as indicated by proteinuria or decreased GFR, also represents sufficient reason to screen for pHTN.