Laura DeCastro

Religiosity/spirituality and pain in patients with sickle cell disease

Religion/spirituality has been identified by individuals with sickle cell disease (SCD) as an important factor in coping with stress and in determining quality of life. Research has demonstrated positive associations between religiosity/spirituality and better physical and mental health outcomes. However, few studies have examined the influence religiosity/spirituality has on the experience of pain in chronically ill patients. Our aim was to examine three domains of religiosity/spirituality (church attendance, prayer/Bible study, intrinsic religiosity) and evaluate their association with measures of pain. We studied a consecutive sample of 50 SCD outpatients and found that church attendance was significantly associated with measures of pain. Attending church once or more per week was associated with the lowest scores on pain measures. These findings were maintained after controlling for age, gender, and disease severity. Prayer/Bible study and intrinsic religiosity were not significantly related to pain in our study. Positive associations are consistent with recent literature, but our results expose new aspects of the relationship for African American patients. We conclude that religious involvement likely plays a significant role in modulating the pain experience of African American patients with SCD and may be an important factor for future study in other populations of chronically ill pain sufferers.

An Official American Thoracic Society Clinical Practice Guideline: Diagnosis, Risk Stratification, and Management of Pulmonary Hypertension of Sickle Cell Disease

BACKGROUND In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality. METHODS A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations. Target audiences include all clinicians who take care of patients with SCD. RESULTS Mortality risk stratification guides decision making. An increased risk for mortality is defined as a TRV equal to or greater than 2.5 m/second, an NT-pro-BNP level equal to or greater than 160 pg/ml, or RHC-confirmed PH. For patients identified as having increased mortality risk, we make a strong recommendation for hydroxyurea as first-line therapy and a weak recommendation for chronic transfusions as an alternative therapy. For all patients with SCD with elevated TRV alone or elevated NT-pro-BNP alone, and for patients with SCD with RHC-confirmed PH with elevated pulmonary artery wedge pressure and low pulmonary vascular resistance, we make a strong recommendation against PAH-specific therapy. However, for select patients with SCD with RHC-confirmed PH who have elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure, we make a weak recommendation for either prostacyclin agonist or endothelin receptor antagonist therapy and a strong recommendation against phosphodiesterase-5 inhibitor therapy. CONCLUSIONS Evidence-based recommendations for the management of patients with SCD with increased mortality risk are provided, but will require frequent reassessment and updating.

Exposure to Hydroxyurea and Pregnancy Outcomes in Patients With Sickle Cell Anemia

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) was a randomized double-blind placebo-controlled trial to test whether hydroxyurea could reduce the rate of painful crises in adults who had at least 3 painful crises per year. Because hydroxyurea is known to be carcinogenic, mutagenic, and teratogenic in animals, a major inclusion criterion in MSH was the use of contraceptives both by females and males in order to avoid exposure of the fetus to hydroxyurea. Despite this precautionary measure, some women became pregnant while taking hydroxyurea or their male partners were on hydroxyurea. We followed surviving patients who were enrolled in the original MSH trial for up to 17 years postrandomization. Our findings suggest that exposure of the fetus to hydroxyurea does not cause teratogenic changes in those pregnancies that terminate in live birth whether full-term or premature. This seems to be true whether the parent taking hydroxyurea was the mother or the father. The same argument seems to apply for exposure to opioids. However, it will take a much longer follow-up of many more hydroxyurea-exposed sickle cell disease subjects to establish the results conclusively.

Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia

Background Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease. Methods We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions. Results The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied. Conclusions GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing. Trial Registration ClinicalTrials.gov NCT00911495

Depression, Suicidal Ideation, and Attempts in Black Patients With Sickle Cell Disease

There is a strong relationship between suicidal ideation, suicide attempts, and depression. Rates of successful suicides are relatively high among the chronically ill compared to other populations but are reduced with treatment. Depression and suicide rates also often differ among blacks as compared to other populations. Using survey methods, we evaluated self-reported rates of depression, suicidal ideation, and suicide attempts in 30 male and 37 female black patients with sickle cell disease (SCD). SCD is a condition characterized by chronic, unpredictable pains and psychosocial distress. Thirty-six percent of the sample self-reported depression in the past 30 days, while 22 percent of the sample exhibited scores on the Beck Depression Inventory indicative of mild or greater depression (mean BDI, 8.31 +/- 7.79). Twenty-nine percent of patients indicated an episode of suicidal ideation and 8%, a suicidal attempt in their lifetime. Thirty-three percent reported treatment by a mental health professional. We conclude that there is a continuing need for mental health services in the management of depressed affect and risk for suicide among patients with SCD. Standards of clinical care must remain flexible to accommodate the mental health needs of this population of patients.

Disparity in the management of iron overload between patients with sickle cell disease and thalassemia who received transfusions.

BACKGROUND: Transfusion therapy is frequently used to prevent morbidity in sickle cell disease (SCD), and subsequent iron overload is common. The objective of this study was to evaluate the current standard of care in monitoring iron overload and related complications in patients with SCD compared to thalassemia (Thal).

Evaluation of a train-the-trainer workshop on sickle cell disease for ED providers.

OBJECTIVE (1) Determine the difference in pre-test and post-test knowledge scores for attendees of a train-the-trainer workshop and (2) determine the number of attendees who disseminated the content within 6 months of attending the workshop. METHODS A 1-day, train-the-trainer workshop focusing on sickle cell disease (SCD) was developed. ED nurses and physicians from the emergency departments with the highest number of patients with SCD were invited to participate at no cost. A panel consisting of 6 SCD and ED experts planned the workshop and developed 20 items for pre-test and post-test knowledge evaluation. The pre-test and post-test were administered at the beginning and end of the workshop, respectively. All attendees received a flash drive with all conference materials and were asked to disseminate workshop content to other ED colleagues. After 6 months, a brief survey was sent to the participants using Survey Monkey asking the number and type of providers trained. RESULTS Fifty-five participants attended the workshop. The mean (SD) pre-test score for the entire cohort was 13 (2) and the post-test score was 16 (2); mean difference (95% CI) 2.96 (2.36, 3.57). Items that scored low included questions dealing with pathophysiologic complications, addiction, or ED utilization. Eighteen participants completed the 6-month follow-up survey. Seven participants reported disseminating workshop content to a total of 99 providers. CONCLUSION A train-the-trainer workshop specifically designed for emergency physicians and nurses that discussed the broad spectrum of SCD was well attended, and 6 months later, 99 additional providers received training.

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.

The Association of Optimism and Perceived Discrimination With Health Care Utilization in Adults With Sickle Cell Disease

OBJECTIVE We evaluated the effect of perceived discrimination, optimism, and their interaction on health care utilization among African American adults with sickle cell disease (SCD). METHODS Measures of optimism and perceived discrimination were obtained in 49 African American SCD patients. Multiple regression analyses controlling for sex and age tested effects of optimism and perceived discrimination on the number of emergency department visits (ED) and number and duration of hospitalizations over the past year. RESULTS A perceived discrimination-optimism interaction was associated with number of emergency departments visits (b = .29, p = .052), number of hospitalizations (b = .36, p = .019), and duration of hospitalizations (b = .30, p = .045) such that those with high perceived discrimination/high optimism had the greatest health care utilization. CONCLUSIONS African American SCD patients with high perceived discrimination/high optimism had greater health care utilization than patients who reported either low perceived discrimination or low optimism. This study suggests that patient personality and coping styles should be considered when evaluating the effects of stress on SCD-related outcomes.