RESUMEN
BACKGROUND: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. METHODS: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. RESULTS: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSß0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSß0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSß0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. DISCUSSION: In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSß0-thalassemia but is dependent on adherence level.
Asunto(s)
Anemia de Células Falciformes , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/epidemiología , Niño , Preescolar , Costos y Análisis de Costo , Servicio de Urgencia en Hospital , Hospitalización , Humanos , Hidroxiurea/uso terapéutico , Lactante , Recién Nacido , Persona de Mediana Edad , Adulto JovenRESUMEN
EXpanding Treatment for Existing Neurological Disease (EXTEND) investigated whether hydroxycarbamide lowers transcranial Doppler (TCD) velocities in Jamaican children with sickle cell anaemia (SCA) and elevated TCD velocity with or without previous stroke. Forty-three children (age 2-17 years) with baseline maximum time-averaged mean velocity (TAMV) ≥ 170 cm/s were stratified into three risk categories based on treatment status and stroke history: Group 1 (no history of stroke, on hydroxycarbamide, n = 12); and Groups 2 (no stroke, no hydroxycarbamide, n = 21) and 3 (previous stroke, no hydroxycarbamide, n = 10). Open-label hydroxycarbamide at 20 mg/kg/day was commenced, with escalation to maximum tolerated dose (MTD) based on mild marrow suppression (average dose 25·4 ± 4·5 mg/kg/day). TCD was performed every six months with brain magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) at baseline and after 18-months of hydroxycarbamide. The maximum TAMV decreased significantly compared to baseline (24 ± 30 cm/s, P < 0·0001), with similar declines in all groups. Clinical stroke occurred in five children, one in Group 1, none in Group 2, and four in Group 3, P = 0·0032, comparing group incidence rates. Brain MRI/MRA was stable in children without clinical stroke. EXTEND documents the feasibility and benefits of hydroxycarbamide at MTD to lower TCD velocities and reduce stroke risk in children with SCA and no history of primary stroke in low-resource settings without transfusion management.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Circulación Cerebrovascular , Trastornos Cerebrovasculares/etiología , Hidroxiurea/uso terapéutico , Ultrasonografía Doppler Transcraneal , Adolescente , Anemia de Células Falciformes/fisiopatología , Velocidad del Flujo Sanguíneo , Trastornos Cerebrovasculares/fisiopatología , Niño , Preescolar , Femenino , Humanos , Incidencia , Jamaica , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Estudios Prospectivos , Recurrencia , Método Simple Ciego , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & controlRESUMEN
Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested.
Asunto(s)
Anemia de Células Falciformes/sangre , Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Metabolómica , Ácidos/sangre , Síndrome Torácico Agudo/etiología , Adolescente , Aminoácidos/sangre , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/farmacología , Arteriopatías Oclusivas/etiología , Biomarcadores , Butiratos/sangre , Niño , Cromatografía Líquida de Alta Presión , Creatina/sangre , Creatinina/sangre , Femenino , Humanos , Hidroxiurea/farmacología , Lisofosfolípidos/sangre , Masculino , Espectrometría de Masas , Lípidos de la Membrana/sangre , Modelos Biológicos , Resonancia Magnética Nuclear Biomolecular , Esfingosina/análogos & derivados , Esfingosina/sangreRESUMEN
Hypoxia and hemoglobin S polymerization are two triggers responsible for initiating erythrocyte sickling and the consequent clinical sickle cell anemia (SCA) events. The objective of this study was to investigate the expression of hypoxia-responsive genes in SCA, testing for correlation with the clinical-laboratorial characteristics of the patient and hydroxyurea therapy. Our results showed, for the first time, a significantly increased expression of HIF-1α and VEGF genes in patients with SCA and an inverse dose-response relationship with hydroxyurea therapy. These results suggest that hypoxic stress may be involved in both the severity of SCA and its response to treatment.
Asunto(s)
Hidroxiurea/uso terapéutico , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Hipoxia/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/metabolismo , Anemia de Células Falciformes/patología , Antidrepanocíticos/uso terapéutico , Estudios de Casos y Controles , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Hipoxia/sangre , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto JovenRESUMEN
A 12-year-old Rottweiler dog was presented with a history of prostration, weight loss and hyporexia for six months. Based on complete blood tests (hematological and biochemical analyses), bone marrow examination and imaging analysis, a diagnosis of chronic myeloid leukemia was made. Treatment with hydroxyurea at a dosage of 18â¯mg/kg twice daily was not effective in controlling the high count of white blood cells. Furthermore, after 35 days of hydroxyurea treatment, the animal developed onycholysis, with sloughing of the claws of the left pelvic and left thoracic limbs and exposure of the distal phalanx. Interruption of the medication was implemented, with clinical healing of the ungual lesions observed three months after initiation of the drug. White blood cells returned to normal after using cyclophosphamide. Currently, the animal is in complete remission, having a disease-free interval of 575 days without chemotherapy. To the authors' knowledge, this is the first report of hydroxyurea-induced onycholysis within a short-term period in a dog diagnosed with chronic myeloid leukemia.