17 research outputs found
Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease
Opioid Doses and Acute Care Utilization Outcomes for Adults with Sickle Cell Disease: Emergency Department versus Acute Care Unit
Background
Acute care units (ACUs) with focused sickle cell disease (SCD) care have been shown to effectively address pain and limit hospitalizations compared to emergency departments (ED), the reason for differences in admission rates is understudied. Our aim was compare effects of usual care for adult SCD pain in ACU and ED on opioid doses and discharge pain ratings, hospital admission rates and lengths of stay.
Methods
In a retrospective, comparative cohort, single academic tertiary center study, 148 adults with sickle cell pain received care in the ED, ACU or both. From the medical records we documented opioid doses, unit discharge pain ratings, hospital admission rates, and lengths of stay.
Findings
Pain on admission to the ED averaged 8.7 Ā± 1.5 and to the ACU averaged 8.0 Ā± 1.6. The average pain on discharge from the ED was 6.4 Ā± 3.0 and for the ACU was 4.5 Ā± 2.5. 70% of the 144 ED visits resulted in hospital admissions as compared to 37% of the 73 ACU visits. Admissions from the ED or ACU had similar inpatient lengths of stay. Significant differences between ED and ACU in first opioid dose and hourly opioid dose were noted.
Conclusions
Applying guidelines for higher dosing of opioids for acute painful episodes in adults with SCD in ACU was associated with improved pain outcomes and decreased hospitalizations, compared to ED. Adoption of this approach for SCD pain in ED may result in improved outcomes, including a decrease in hospital admissions
Improved health care utilization and costs in transplanted versus non-transplanted adults with sickle cell disease.
Patients with sickle cell disease (SCD) have access to fewer health care resources and therapies compared to other diseases, which contributes to increased morbidity and health care utilization. We compared health care utilization (inpatient hospital days, emergency care visits) and health care-related costs between SCD adults that underwent hematopoietic stem cell transplantation (HSCT) using a nonmyeloblative conditioning regimen versus those referred for HSCT but did not proceed due to lack of an HLA-matched sibling donor, denial by insurance, red blood cell antibodies to the potential donor, or declining further evaluation. Between 8/2011 and 4/2016, 83 SCD patients were referred for allogeneic HSCT and 16 underwent the procedure. The HSCT and non-HSCT groups were similar by age, sex, prior SCD-related therapy and complications. Compared to pre HSCT, significantly fewer inpatient hospital days (median of 1 versus 22 days, P = 0.003) and emergency care visits (median of 1 versus 4 visits, P = 0.04) were observed by the 2nd year post-HSCT. Similar results were observed in comparison to the standard-of-care group (median of 1 versus 12 hospital days, P = 0.002; median of 1 versus 3 emergency visits, P = 0.03). Lower health care costs were observed by the 2nd year post-HSCT (median of 64,634 pre-HSCT (P = 0.01) and versus 20,833/patient/year (IQR, -4,442/patient/year) in health care costs compared to pre-HSCT was observed in the 2nd year post-HSCT. In conclusion, allogeneic HSCT leads to improvements in health care utilization and costs compared to standard-of-care therapy in high-risk SCD adults
Non-Myeloablative Haploidentical Peripheral Blood Stem Cell Transplantation in Adult Patients with Sickle Cell Disease
Genetic polymorphism of APOB is associated with diabetes mellitus in sickle cell disease
Environmental variations have strong influences in the etiology of type 2 diabetes mellitus. In this study, we investigated the genetic basis of diabetes in patients with sickle cell disease (SCD), a Mendelian disorder accompanied by distinct physiological conditions of hypoxia and hyperactive erythropoiesis. Compared to the general African American population, the prevalence of diabetes as assessed in two SCD cohorts of 856 adults was low, but it markedly increased with older age and overweight. Meta-analyses of over 5 million single-nucleotide polymorphisms (SNPs) in the two SCD cohorts identified a SNP, rs59014890, the C allele of which associated with diabetes risk at P = 3.2 Ć 10ā8 and, surprisingly, associated with decreased APOB expression in peripheral blood mononuclear cells (PBMCs). The risk allele of the APOB polymorphism was associated with overweight in 181 SCD adolescents, with diabetes risk in 592 overweight, non-SCD African Americans ā„45 years of age, and with elevated plasma lipid concentrations in general populations. In addition, lower expression level of APOB in PBMCs was associated with higher values for percent hemoglobin A1C and serum total cholesterol and triglyceride concentrations in patients with Chuvash polycythemia, a congenital disease with elevated hypoxic responses and increased erythropoiesis at normoxia. Our study reveals a novel, environment-specific genetic polymorphism that may affect key metabolic pathways contributing to diabetes in SCD
Integration of neuropsychology services in a sickle cell clinic and subsequent healthcare use for pain crises
Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study
<div><p>Background</p><p>Sickle cell disease (SCD), a congenital hemolytic anemia that exacts terrible global morbidity and mortality, is driven by polymerization of mutated sickle hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) interferes with this polymerization, but HbF is epigenetically silenced from infancy onward by DNA methyltransferase 1 (DNMT1).</p><p>Methods and findings</p><p>To pharmacologically re-induce HbF by DNMT1 inhibition, this first-in-human clinical trial (NCT01685515) combined 2 small moleculesādecitabine to deplete DNMT1 and tetrahydrouridine (THU) to inhibit cytidine deaminase (CDA), the enzyme that otherwise rapidly deaminates/inactivates decitabine, severely limiting its half-life, tissue distribution, and oral bioavailability. Oral decitabine doses, administered after oral THU 10 mg/kg, were escalated from a very low starting level (0.01, 0.02, 0.04, 0.08, or 0.16 mg/kg) to identify minimal doses active in depleting DNMT1 without cytotoxicity. Patients were SCD adults at risk of early death despite standard-of-care, randomized 3:2 to THUādecitabine versus placebo in 5 cohorts of 5 patients treated 2X/week for 8 weeks, with 4 weeks of follow-up. The primary endpoint was ā„ grade 3 non-hematologic toxicity. This endpoint was not triggered, and adverse events (AEs) were not significantly different in THU-decitabineāversus placebo-treated patients. At the decitabine 0.16 mg/kg dose, plasma concentrations peaked at approximately 50 nM (C<sub>max</sub>) and remained elevated for several hours. This dose decreased DNMT1 protein in peripheral blood mononuclear cells by >75% and repetitive element CpG methylation by approximately 10%, and increased HbF by 4%ā9% (<i>P</i> < 0.001), doubling fetal hemoglobin-enriched red blood cells (F-cells) up to approximately 80% of total RBCs. Total hemoglobin increased by 1.2ā1.9 g/dL (<i>P</i> = 0.01) as reticulocytes simultaneously decreased; that is, better quality and efficiency of HbF-enriched erythropoiesis elevated hemoglobin using fewer reticulocytes. Also indicating better RBC quality, biomarkers of hemolysis, thrombophilia, and inflammation (LDH, bilirubin, D-dimer, C-reactive protein [CRP]) improved. As expected with non-cytotoxic DNMT1-depletion, platelets increased and neutrophils concurrently decreased, but not to an extent requiring treatment holds. As an early phase study, limitations include small patient numbers at each dose level and narrow capacity to evaluate clinical benefits.</p><p>Conclusion</p><p>Administration of oral THU-decitabine to patients with SCD was safe in this study and, by targeting DNMT1, upregulated HbF in RBCs. Further studies should investigate clinical benefits and potential harms not identified to date.</p><p>Trial registration</p><p>ClinicalTrials.gov, <a target="_blank">NCT01685515</a></p></div
Adverse events (AEs).
<p><b>(A)</b> AEs with possible relatedness to the study drug (AEs other than āunrelatedā) per judgement of the treating clinical teams. <b>(B)</b> All grade 3 AEs occurring in study drugāand placebo-treated patients. These grade 3 AEs were sickle cell complications judged to be unrelated to the study drug by the treating clinical teams. <b>(C)</b> Statistical comparison of grade 3 AEs between placebo and decitabine dose-level patients. R function poisson.test(), an exact test, was used. Abbreviation: ED/Hosp, emergency department/hospital.</p