Time to pain relief: A randomized controlled trial in the emergency department during vaso-occlusive episodes in sickle cell disease.

OBJECTIVE: Compare time to pain relief (minimum of a 13 mm and 30% reduction) during an Emergency Department (ED) visit among patients with sickle cell disease (SCD) experiencing severe pain associated with a vaso-occlusive episode who were randomized to receive either an individualized or weight-based pain protocol. METHODS: A randomized controlled trial in two EDs. Adults with sickle cell disease. Research staff recorded pain scores every 30 min during an ED visit (up to 6 h in the ED) using a 0-100 mm visual analogue scale. Analysis included 122 visits, representing 49 patients (individualized: 61 visits, 25 patients; standard: 61 visits, 24 patients). RESULTS: Pain reduction across 6-h was greater for the individualized compared to the standard protocol (protocol-by-time: p = .02; 6-h adjusted pain score comparison: Individualized: M = 29.2, SD = 38.8, standard: M = 45.3, SD = 35.6; p = .03, Cohen d = 0.43). Hazards models indicated a greater probability of 13 mm (HR = 1.54, 95% CI = 1.05, 2.27, p = .03) and 30% (HR = 1.71, 95% CI = 1.11, 2.63, p = .01) reduction in the individualized relative to the standard protocol. CONCLUSIONS: Patients who received treatment with an individualized protocol experienced a more rapid reduction in pain, including a 13 mm and 30% reduction in pain scores when compared to those that received weight-based dosing.

Myeloid neoplasms in the setting of sickle cell disease: an intrinsic association with the underlying condition rather than a coincidence; report of 4 cases and review of the literature.

Myeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age at time of diagnosis ranged from 27 to 59 years with a median of 35.5 years. Two patients were treated with hydroxyurea and the other two with supportive care alone, with one out of the four patients receiving additional treatment with hematopoietic stem cell transplant. Three patients presented with leukocytosis, and the remaining patient presented with pancytopenia. Two patients were diagnosed with myelodysplastic syndrome/myeloproliferative neoplasm, one with myelodysplastic syndrome, and the other with acute myeloid leukemia. All four cases demonstrated certain degrees of myelodysplasia and complex cytogenetic abnormalities with - 7/7q- and/or - 5/5q- or with 11q23 (KMT2A) rearrangement. This cytogenetic profile resembles that seen in therapy-related myeloid neoplasm, suggesting that myeloid neoplasm in the setting of sickle cell disease may represent a subcategory of the disease distinct from de novo myeloid neoplasm in general. Extensive literature review further demonstrates this similarity in cytogenetic profile, as well as in other associated pathologic features. Potential etiology includes therapy for sickle cell disease, disease-related immunomodulation, or disease-related chronic inflammation. We hypothesize that constant hematopoietic hyperplasia, stimulated by a hemolysis-induced cytokine storm, may increase the chance of somatic mutations/cytogenetic aberrations, resulting in transformation of myeloid precursors. This group of myeloid neoplasms seems to herald a dismal clinical outcome, with median survival <1 year, although the exact pathogenesis and biology of the disease remain to be investigated by large cohorts in future studies.

Adults with sickle cell disease may perform cognitive tests as well as controls when processing speed is taken into account: a preliminary case-control study.

AIMS: This study aimed to: (1) evaluate cognitive function among adults with sickle cell disease using a computer-administered neuropsychological test; and (2) replicate previously identified differences in processing speed between patients with sickle cell disease and controls. BACKGROUND: Previous evidence suggests that, compared with controls, adult patients with sickle cell disease have poorer cognitive functioning across most domains but the most significant deficits appear to be in the area of processing speed. DESIGN: Cross-sectional case-control study conducted from June 2008-June 2010. METHODS: Cognitive functioning was measured using computerized, self-administered, neuropsychological tests among 31 patients with sickle cell disease and 17 controls matched for age, gender and race. The assessment averaged 30 minutes and scores were recorded for seven computerized tests: verbal and visual memory, finger tapping, symbol digit coding, Stroop test, shifting attention and continuous performance. RESULTS: Patients with sickle cell disease scored 10·76 points lower on the CNS Vital Signs processing speed domain than controls. Although non-significant, patients scored 5·73 points lower on the full index than controls but after adjusting for processing speed, mean scores for patients were 3 points greater compared with controls. Differences in executive functioning and attention were not significant and memory did not differ between groups. CONCLUSION: Using a brief, computer-administered 30-minute neuropsychological test, we were able to replicate previous findings showing a greater than 10-point deficit in processing speed among patients with sickle cell disease. When differences in processing speed are taken into account, patients perform equally well or better than controls on cognitive tasks.

Kikuchi-Fugimoto's disease in sickle cell disease: report of 2 cases.

Kikuchi-Fugimoto's Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is most frequently seen in young women and has been associated with autoimmune disorders such as polymyositis and systemic lupus erythematosus. It is generally a self-limiting disease with recovery time ranging from weeks to months. A typical presentation of KFD includes painful cervical lymphadenopathy, usually consisting of unilateral involvement of the posterior cervical chain. To date, this condition has not been described in patients with sickle cell disease. We present 2 cases of KFD, 1 in a patient with sickle beta(o)-thalassemia (Sbeta(o)thal) and 1 in a patient with sickle cell anemia with hereditary persistence of fetal hemoglobin (HbS-HPFH). Both patients were young-adult African American females who presented with fever and unilateral tender cervical lymphadenopathy. Extensive infectious disease testing, including cultures and viral serologies, were all negative. Imaging was negative for abscesses. The first patient had a preceding history of benign carcinoid tumor and idiopathic thrombocytopenic purpura. The second patient had no history of autoimmune syndromes but was on hydroxyurea therapy at the time of her presentation; the first had never taken hydroxyurea. Treatment strategies included prednisone therapy in the first case and watchful monitoring in the second. Recovery time was approximately 2 months for each patient. Both developed thyroid disease subsequent to their episode of KFD. Currently, both patients are asymptomatic with no recurrence of KFD or active autoimmune disease.

Opioid management and dependency among adult patients with sickle cell disease.

While pain is one of the most debilitating symptoms of sickle cell disease, narcotics remain an effective although controversial widely practiced intervention. Vaso-occlusive crises are the most common cause for seeking pharmacological treatment. The influence of stigmatization and pseudo addiction in emergency departments and outpatient clinics was reviewed. We analyzed patterns of narcotic utilization in a sample of 63 adult patients with sickle cell disease to determine if their psychological functioning and reports of pain differed as a function of the primary narcotics they were taking for oral pain management. Fifty-one percent of patients reported treatment of Oxycodone, 35% OxyContin, 24% methadone and 11% morphine. Patients who were treated with Oxycodone reported greater sensory reactions to pain (p = 0.001), visual analog scale (VAS) (p = 0.02), and averaged weekly pain intensity ratings than patients who did not use this medication. There were no differences in pain or affective response in patients treated with OxyContin, methadone or morphine. We suggest there are clear differences between the reports of pain in patients with sickle cell disease taking short-acting narcotics for pain management as compared to those who are not, a pattern that does not distinguish patients who are managed with long-acting preparations. We discuss the relevance of addressing narcotic management in the context of the perception of health care providers and patients with sickle cell disease.

Neurocognitive testing and functioning in adults sickle cell disease.

The impact of cerebrovascular events (CVE) on cognitive functioning in adults with sickle cell disease is not well understood. Sequelae of CVEs can adversely impact their quality of life. We reviewed neurocognitive presentation and testing in adults with sickle cell disease. We evaluated the frequency of complaints of memory disturbance using survey methodology in a sample of 109 adult patients with sickle cell disease (48 males, 61 females). A subsample of 24 patients also received a memory questionnaire where specific cognitive functions were assessed. Overall, we found that males and females did not differ in the frequency of experienced memory disturbance during painful crises. However, the frequency of men reporting that their ability to remember where they place common objects such as keys (p = 0.017) and remembering the item they intended to buy in a grocery store or pharmacy (p = 0.048) was worse now compared to when they were in high school and was greater when compared to women. The frequency of men who reported their memory was worse now than when they were in high school (p = 0.051) was also greater than in women. We concluded that memory dysfunction predicts global monthly presentation of pain. We suggest incorporating cost-effective neurocognitive screening measures as a standard of practice in sickle cell disease.

Adherence to Iron Chelation Therapy with Deferasirox Formulations among Patients with Sickle Cell Disease and ß-thalassemia.

BACKGROUND: Individuals with hemoglobinopathies experience complications that often require management with multiple transfusions. These chronic transfusions can lead to iron overload, which places them at increased risk of organ damage, malignancy, and even death. Deferasirox is the most common iron chelator used to treat iron overload due to its safety, efficacy, and oral administration. The first formulation of deferasirox, a dispersible tablet for oral suspension (DT) called Exjade®, was associated with adherence challenges due to complaints from poor taste and side effects such as abdominal discomfort. A new film-coated tablet formulation (FCT) called Jadenu® was subsequently developed to overcome these challenges. OBJECTIVE: The objective of this study was to compare adherence rates between formulations of deferasirox (DT versus FCT) and describe associations between adherence to chelation therapy and changes in hematological parameters among patients with SCD and ß-thalassemia. METHODS: In this retrospective study of 20 children and adults with sickle cell disease (SCD) and ß-thalassemia with iron overload, we compared adherence rates for deferasirox DT versus deferasirox FCT. We reviewed data from the electronic medical record and pharmacy expense reports between 2014 and 2018. We calculated the mean medication possession ratio (MPR) and analyzed the mean paired difference in MPR and ferritin levels using paired sample t-test. RESULTS: The overall mean MPR was 0.15 (0.25) for deferasirox DT and 0.44 (0.32) for deferasirox FCT. The mean paired difference in MPR when transitioning from deferasirox DT to deferasirox FCT was +0.29, p-value < 0.01 (95% CI: 0.19, 0.39). The mean paired difference in ferritin while on deferasirox DT compared to ferritin 6 months after transitioning to deferasirox FCT was -306 ng/mL p-value = 0.14 (95% CI: 719, 113). CONCLUSION: There was significant improvement in adherence to iron chelation therapy when patients transitioned from deferasirox DT to deferasirox FCT.

Exploring Emergency Department Provider Experiences With and Perceptions of Weight-Based Versus Individualized Vaso-Occlusive Treatment Protocols in Sickle Cell Disease.

Treatment of vaso-occlusive episodes (VOEs) is the most common reason for emergency department (ED) treatment of sickle cell disease (SCD). We (1) compared perceptions of the usability and ability to manage VOE pain between ED nurses and other ED provider types, ED sites, and VOE protocols (individualized vs. weight-based), and (2) identified ED nurse and other provider protocol suggestions. A secondary analysis of provider survey data collected immediately after caring for a patient enrolled in a randomized controlled trial comparing weight-based versus individualized opioid dosing for VOE. Research staff asked the ED nurses and other ED providers (nurse practitioners [NPs], physician assistants [PAs], residents, and attending physicians) 5 questions related to the protocol's ease of use and ability to manage pain. There were 236 surveys completed. Attending physicians (n = 15), residents (n = 88), PAs (n = 21), and NPs (n = l) were more satisfied than nurses (n = 111) with the clarity of the analgesic ordering (97.6% vs. 0%, p = 0.0001) and ability to manage the patient's VOE pain (91% vs. 0%, p = 0.0001). When comparing both protocols with the usual ED strategy in their ED to manage VOE, more nurses than other ED providers perceived the study patients' pain management protocol as better (100% vs. 35.2%, p = 0.0001). Other ED providers perceived the individualized versus weight-based protocol as better at managing pain than their usual ED strategy (70.3% vs. 59.5%, p = 0.04). The individualized protocol was perceived as better in managing VOE than the weight-based ED strategy. While physicians were satisfied with the clarity of the protocols, nurses were not. Improved protocol usability is required for widespread ED implementation.

A 19-year-old man with sickle cell disease presenting with spinal infarction: a case report.

INTRODUCTION: Vasculopathy of the large vessels commonly occurs in sickle cell disease, and as a result cerebral infarction is a well characterized complication of this condition. However, spinal infarction appears to be rare. Spinal infarct is infrequent in the non-sickle cell population as well, and accounts for only about 1 percent of all central nervous system infarcts. CASE PRESENTATION: In the present work, we report the case of a 19-year-old African-American man with sickle cell disease who experienced an anterior spinal infarct and subsequent quadriplegia. He was incidentally noted to be a heterozygote for factor V Leiden. We also reviewed the literature and found two previous cases of spinal cord infarction and sickle hemoglobin. Our literature search did not demonstrate that heterozygocity for factor V Leiden plays an important role in spinal cord infarction. CONCLUSIONS: The paucity of cases associated with sickle hemoglobin does not allow us to postulate any particular risk factors with sickle cell disease that might predispose patients to spinal cord infarction. Our patient's case raises the question as to whether spinal cord infarction is being missed in individuals with sickle cell disease and neurologic symptoms.