RESUMEN
BACKGROUND: Suboptimal medication adherence is common across youth with chronic health conditions and may contribute to health disparities and adverse health outcomes, especially in underserved communities. METHODS: Using pharmacy prescription records and guided by the World Health Organization Multidimensional Adherence Model, we examined patient-, treatment-, and health system-related factors that may affect hydroxyurea adherence in 72 youth with sickle cell disease (SCD), 10-18 years who had participated in the multisite "Hydroxyurea Adherence for Personal Best in SCD" (HABIT) feasibility (6 months) and efficacy (12 months) trials. Pharmacy data were collected from the year prior to study entry through the duration of each trial. We also examined hydroxyurea dose at baseline, prescribing patterns (hydroxyurea formulation and dose prescribed), quantity of hydroxyurea dispensed, and number of daily capsules/tablets prescribed. Data were analyzed using descriptive statistics. RESULTS: On average, youth were prescribed 1095 ± 402 mg hydroxyurea per day, requiring ingestion of 3 or more capsules for 39.4% of youth. Frequently identified potential barriers were complex medication regimens in which dose of hydroxyurea differed by day of week (47.2%); receipt of an inadequate (< 30 days) supply of hydroxyurea from the pharmacy ≥ 3 times during record collection period (29.2%); and prescription of hydroxyurea suspension suggesting problems swallowing capsules (22.2%). In this sample, most youth were exclusively prescribed 500 mg capsules (62.5%), which was associated with complex medication regimens (RR 3.0, 95% CI 1.4-6.7). Potential barriers were common, occurred at all levels and are potentially modifiable with targeted interventions at the treatment- and health system-related levels.
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Anemia de Células Falciformes , Antidrepanocíticos , Hidroxiurea , Cumplimiento de la Medicación , Humanos , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Anemia de Células Falciformes/tratamiento farmacológico , Adolescente , Masculino , Niño , Femenino , Cumplimiento de la Medicación/estadística & datos numéricos , Antidrepanocíticos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricosRESUMEN
Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at therapeutic dose in human medicine. A 2.5-year-old female spayed mixed breed dog was presented for acute signs of neurologic disease and diagnosed with severe erythrocytosis without an identified underlying cause, leading to suspicion of polycythemia vera. The dog was managed with phlebotomies, supportive care, and administration of hydroxyurea. Within 2 h of administration of hydroxyurea (37 mg/kg) administration, respiratory distress with cyanosis, and methemoglobinemia developed. Signs resolved within 24 h but recurred after a second administration of lower dosage of hydroxyurea (17 mg/kg) 20 days later. The dog remained asymptomatic except for mild cyanosis but was humanely euthanized for lack of relevant improvement of signs of neurologic disease. This case report documents the repeated occurrence of methemoglobinemia in a dog after administration of hydroxyurea at therapeutic doses.
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Enfermedades de los Perros , Hidroxiurea , Metahemoglobinemia , Perros , Animales , Hidroxiurea/efectos adversos , Hidroxiurea/administración & dosificación , Hidroxiurea/uso terapéutico , Metahemoglobinemia/veterinaria , Metahemoglobinemia/inducido químicamente , Femenino , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológicoRESUMEN
Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness. Video directly observed therapy (VDOT) has shown promise as an adherence-promoting intervention for hydroxyurea, yet previous VDOT trials were limited by high attrition from gaps in technology access, use of unvalidated adherence measures, and healthcare system limitations of delivering VDOT to patients. As such, we fostered a small business partnership to compare VDOT for hydroxyurea to attention control to address previous shortcomings, promote equitable trial participation, and maximize scalability. VDOT will be administered by Scene Health (formerly emocha Health) and adherence monitoring will be performed using a novel electronic adherence monitor developed to meet the unique needs of the target population. Adolescent and young adult patients as well as caregivers of younger patients (<11 years of age) will be recruited. In addition to visit incentives, all participants will be offered a smartphone with a data plan to ensure all participants have equal opportunity to complete study activities. The primary objectives of this pilot, multi-center, randomized controlled trial (RCT) are to assess retention and sustained engagement and to explore needs and preferences for longer-term adherence monitoring and interventions. This RCT is registered with the National Institutes of Health (NCT06264700). Findings will inform a future efficacy RCT applying VDOT to hydroxyurea to address adherence gaps and improve outcomes within this vulnerable population.
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Anemia de Células Falciformes , Hidroxiurea , Humanos , Anemia de Células Falciformes/tratamiento farmacológico , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Adolescente , Niño , Cumplimiento de la Medicación , Adulto Joven , Antidrepanocíticos/uso terapéutico , Masculino , Femenino , AdultoRESUMEN
Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.
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Interferón alfa-2 , Interferón-alfa , Policitemia Vera , Polietilenglicoles , Proteínas Recombinantes , Humanos , Policitemia Vera/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interferón-alfa/administración & dosificación , Polietilenglicoles/uso terapéutico , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Interferón alfa-2/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Femenino , Anciano , Selección de Paciente , Resultado del Tratamiento , Adulto , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificaciónRESUMEN
Nonmyeloablative, matched sibling donor hematopoietic stem cell transplantation with alemtuzumab/total body irradiation (TBI) conditioning is a curative therapy with low toxicity for adults with sickle cell disease (SCD). However, relatively low donor chimerism levels and graft rejection remain important challenges. We hypothesized that adding azathioprine/hydroxyurea preconditioning will improve donor chimerism levels and reduce graft failure rate. In this prospective cohort study, we enrolled consecutive adult patients with SCD undergoing matched sibling donor transplantation at the Amsterdam UMC. Patients received azathioprine 150 mg/day and hydroxyurea 25 mg/kg/day for 3 months prior to alemtuzumab 1 mg/kg and 300 cGy TBI conditioning. Twenty patients with SCD (median age 26 years [range 19-49], 13 females) were transplanted. Median follow-up was 46.0 months (IQR 21.8-57.9). One-year overall survival and event-free survival (graft failure or death) were both 95% (95% confidence interval 86-100). Mean donor myeloid and T-cell chimerism 1-year post-transplant were 95.2% (SD ±10.6) and 67.3% (±15.3), respectively. One patient (5%) experienced graft failure without autologous regeneration, resulting in infections and death. All other patients had a corrected SCD phenotype and were able to discontinue sirolimus. Three patients were successfully treated with alemtuzumab (1 mg/kg) after the transplant because of declining donor chimerism and cytopenias to revert impending graft rejection. Toxicity was mostly related to sirolimus and alemtuzumab. One patient developed steroid-responsive grade II intestinal acute graft-versus-host disease. Collectively, preconditioning with azathioprine/hydroxyurea prior to nonmyeloablative matched sibling donor transplantation resulted in excellent event-free survival and robust donor T-cell chimerism, enabling the successful withdrawal of sirolimus. ClinicalTrials.gov: NCT05249452.
Asunto(s)
Anemia de Células Falciformes , Azatioprina , Trasplante de Células Madre Hematopoyéticas , Hidroxiurea , Hermanos , Acondicionamiento Pretrasplante , Humanos , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Masculino , Acondicionamiento Pretrasplante/métodos , Estudios Prospectivos , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Persona de Mediana Edad , Anemia de Células Falciformes/terapia , Azatioprina/uso terapéutico , Azatioprina/administración & dosificación , Adulto Joven , Quimera por Trasplante , Alemtuzumab/uso terapéutico , Alemtuzumab/administración & dosificación , Rechazo de Injerto/prevención & control , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
BACKGROUND: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years. METHODS: In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sß zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing. FINDINGS: We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 109 cells per L to 3·6 [2·2] × 109 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths. INTERPRETATION: Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa. FUNDING: US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation.
Asunto(s)
Anemia de Células Falciformes , Antidrepanocíticos , Hidroxiurea , Humanos , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/sangre , Preescolar , Niño , Masculino , Femenino , África del Sur del Sahara , Estudios de Seguimiento , Lactante , Antidrepanocíticos/uso terapéutico , Antidrepanocíticos/efectos adversos , Antidrepanocíticos/administración & dosificación , Resultado del Tratamiento , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: Despite advances in therapeutics for adverse-risk acute myeloid leukaemia (AML), overall survival remains poor, especially in refractory disease. Comprehensive tumour profiling and pre-clinical drug testing can identify effective personalised therapies. CASE: We describe a case of ETV6-MECOM fusion-positive refractory AML, where molecular analysis and in vitro high throughput drug screening identified a tolerable, novel targeted therapy and provided rationale for avoiding what could have been a toxic treatment regimen. Ruxolitinib combined with hydroxyurea led to disease control and enhanced quality-of-life in a patient unsuitable for intensified chemotherapy or allogeneic stem cell transplantation. CONCLUSION: This case report demonstrates the feasibility and role of combination pre-clinical high throughput screening to aid decision making in high-risk leukaemia. It also demonstrates the role a JAK1/2 inhibitor can have in the palliative setting in select patients with AML.
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Toma de Decisiones Clínicas , Ensayos Analíticos de Alto Rendimiento , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Toma de Decisiones Clínicas/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Pirazoles/uso terapéutico , Nitrilos/uso terapéutico , Pirimidinas/uso terapéutico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genéticaRESUMEN
Consistent with studies showing a high prevalence of the Duffy null phenotype among healthy Black Americans, this retrospective study found that Duffy null was present in >75% of a young and contemporary cohort of children with sickle cell disease (SCD) in the United States. Despite the potential for this phenotype to impact absolute neutrophil counts, hydroxyurea (HU) dosing, and outcomes, it was not associated with being prescribed a lower HU dose or having increased acute SCD visits early in the HU treatment course. Future studies are needed to confirm these findings in older children with SCD.
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Anemia de Células Falciformes , Antidrepanocíticos , Sistema del Grupo Sanguíneo Duffy , Hidroxiurea , Humanos , Hidroxiurea/uso terapéutico , Hidroxiurea/administración & dosificación , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Estados Unidos/epidemiología , Niño , Sistema del Grupo Sanguíneo Duffy/genética , Prevalencia , Antidrepanocíticos/uso terapéutico , Lactante , Receptores de Superficie Celular/genética , AdolescenteRESUMEN
Sickle cell anemia or sickle cell disease is an autosomal recessive disease, caused by a mutation in the hemoglobin gene, where glutamic acid is substituted for valine at position 6 of the beta chain of hemoglobin, resulting in hemoglobin S The diagnosis is made with electrophoresis. The clinical manifestations are varied, the most frequent being the vaso-occlusive crisis, which can increase in pregnancy, during which sickle cell disease also increases the risk of maternal-fetal complications, caused by pre-eclampsia infections, intrauterine growth restriction, and premature delivery. and miscarriage. The usual treatment for the management of seizures is hydroxyurea, a drug that is teratogenic, so its use is contraindicated during pregnancy. Other treatment alternatives are red blood cell transfusion and red blood cell exchange. Next, the first case of red blood cell exchange or exchange transfusion in a pregnant patient with sickle cell anemia at the Hospital Regional de Talca is presented.
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Humanos , Masculino , Femenino , Embarazo , Recién Nacido , Adulto , Complicaciones Hematológicas del Embarazo/terapia , Recambio Total de Sangre , Transfusión de Eritrocitos/métodos , Anemia de Células Falciformes/terapia , Complicaciones Hematológicas del Embarazo/prevención & control , Resultado del Embarazo , Hidroxiurea/administración & dosificación , Anemia de Células Falciformes/prevención & controlRESUMEN
ABSTRACT Objective: To describe two cases of unusual variants of sickle cell disease. Case description: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. Comments: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.
RESUMO Objetivo: Descrever dois casos de variantes raras da hemoglobinopatia falciforme. Descrição do caso: Apresentamos aqui dois casos de hemoglobinopatias variantes das células falciformes, de famílias não relacionadas, no estado do Baluchistão (Paquistão), sendo um diagnosticado como doença da hemoglobina SD na eletroforese de hemoglobina, enquanto o outro com doença da hemoglobina SE. Ambos foram diagnosticados a partir da apresentação de osteomielite. Comentários: Hemoglobina SD (Hb SD) e hemoglobina SE (Hb SE) são hemoglobinopatias raras no mundo. A escassez de literatura disponível sugere que ambas são variantes da doença falciforme (DF) com natureza heterogênea. A prevalência de hemoglobinopatia falciforme com heterozigosidade composta foi encontrada com frequência variável na população do sudeste asiático. A frequência de osteomielite na DF é de 12 a 18%, mas sua ocorrência entre as hemoglobinopatias falciformes variantes é pouco relatada. Os dois casos reportados apresentaram osteomielite como característica de apresentação da doença.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Osteomielitis/diagnóstico , Electroforesis de las Proteínas Sanguíneas/métodos , Hemoglobinopatías/genética , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Osteomielitis/etiología , Osteomielitis/tratamiento farmacológico , Pakistán/etnología , Imagen por Resonancia Magnética/métodos , Radiografía/métodos , Tamizaje Masivo/normas , Tamizaje Masivo/ética , Prevalencia , Administración Oral , Resultado del Tratamiento , Administración Intravenosa , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/sangre , Heterocigoto , Hidroxiurea/administración & dosificación , Hidroxiurea/uso terapéutico , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antidrepanocíticos/administración & dosificación , Antidrepanocíticos/uso terapéuticoRESUMEN
Abstract Background: Sickle cell disease (SCD) is an autosomal recessive genetic disease in which a mutation occurs in the β-globin chain gene, resulting in abnormal hemoglobin levels. In an environment with reduced oxygen concentration, red blood cells change their conformation, resulting in chronic hemolysis and consequent anemia and vaso-occlusive crises with injuries to several organs, with a significant impairment of the osteoarticular system. This study aimed to verify the chronic osteoarticular alterations and their association with clinical and laboratory characteristics of patients with SCD with a more severe phenotype (SS and Sβ0), on a steady-state fasis. Methods: Fifty-five patients were referred to a medical consultation with a specialized assessment of the locomotor system, followed by laboratory tests and radiographic examinations. Results: In total, 74.5% patients had hemoglobinopathy SS; 67.3% were female; and 78.2% were non-whites. The mean patient age was 30.5 years. Most patients (61.8%) reported up to three crises per year, with a predominance of high-intensity pain (65.5%). Radiographic alterations were present in 80% patients. A total of 140 lesions were identified, most which were located in the spine, femur, and shoulders. Most lesions were osteonecrosis and osteoarthritis and were statistically associated with the non-use of hydroxyurea. Conclusions: There was a high prevalence of chronic osteoarticular alterations, which was statistically associated only with the non-regular use of hydroxyurea.(AU)
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Humanos , Osteoartritis/etiología , Osteonecrosis/etiología , Enfermedades Óseas Metabólicas/etiología , Hidroxiurea/administración & dosificación , Anemia de Células Falciformes/fisiopatología , Pronóstico , Estudios Transversales/instrumentación , Factores de Riesgo , Hidroxiurea/efectos adversosRESUMEN
OBJECTIVE: The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. METHODS: Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. RESULTS: Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). CONCLUSION: Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Anemia de Células Falciformes , Enfermedad de la Hemoglobina SC , Hidroxiurea/administración & dosificación , Estrés OxidativoRESUMEN
A anemia falciforme é uma doença genética caracterizada pelo alto índice de morbimortalidade, considerada como a mais grave entre as doenças falciformes. As opções terapêuticas mais eficazes atualmente disponíveis para tratamento desta hemoglobinopatia são transplante de medula óssea (TMO) e hidroxiuréia (HU). O TMO apesar de ser a medida curativa é considerado de alto risco por apresentar diversos graus de complicações e significativo nível de mortalidade. O uso de HU em crianças portadoras de anemia falciforme tem proporcionado redução de complicações clínicas e aumento significativo na expectativa de vida, por promover elevação dos níveis de hemoglobina fetal, da concentração de hemoglobina e do VCM, bem como redução da hemólise e de eventos vaso-oclusivos. Desse modo, a HU é considerada como melhor opção terapêutica atualmente disponível. Porém, por ser apontada como droga potencialmente carcinogênica, há questionamentos quanto aos benefícios e toxicidades quando utilizada por longo período. Este trabalho teve como proposta, avaliar por meio da revisão literária, os riscos, benefícios e efeitos adversos da hidroxiuréia em crianças.
Sickle cell anemia is a genetic disease characterized by a high morbimortality rate, it is considered as the most serious among all sickle cell diseases. The most effective therapeutic options available nowadays for the treatment of this hemoglobinopathy are bone morrow transplantation (BMT) and hydroxyurea (HU). BMT is considered a high risk procedure due to the different complications and significant mortality rates. The use of HU for children with sickle cell anemia has reduced the clinical complications and given a significant increase in life expectancy by augmenting the fetal hemoglobin levels and hemoglobin concentrations and reducing cytomegalovirus, as well as reducing hemolysis and vaso-occlusive events. Thus, HU is considered the best therapeutic option currently available. However, as HU has been identified as a potentially carcinogenic drug, there are questions related to the benefits and toxicities when it is used over long periods of time. This work aimed at evaluating, through a review of the literature, the risks, benefits and adverse effects of the use of hydroxyurea in children.
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Humanos , Anemia de Células Falciformes , Eficacia , Hidroxiurea/administración & dosificación , Hidroxiurea/toxicidad , Hidroxiurea/uso terapéuticoRESUMEN
O uso de hidroxiuréia promove a elevação dos níveis de hemoglobina fetal (Hb F) em pacientes portadores de síndromes falciformes (SF) e o medicamento vem sendo estudado em vários grupos de pacientes, incluindo adultos e crianças. O presente trabalho analisou a eficácia e tolerabilidade do uso de hidroxiuréia em crianças na faixa etária entre 5 e 17 anos de idade e em adultos jovens acima de 18 anos, portadores de hemoglobinopatia SS ou Sbeta0 que foram acompanhados regularmente no ambulatório do Hospital Hemope. Os pacientes pediátricos foram tratados com dose inicial de hidroxiuréia de 10 mg/kg/dia, a qual era aumentada em 5 mg/kg por dia em intervalos de oito semanas, até a dose máxima de 25 mg/kg/dia. Para os adultos, o tratamento foi iniciado com 500 mg/dia de hidroxiuréia até a dose máxima de 1g/dia. Foi observada redução do número de crises álgicas assim como do número de internações hospitalares, elevação do nível de Hb F e do Volume Corpuscular Médio, no grupo pediátrico. Entre os pacientes maiores de 18 anos, também se observou melhora clínica e significância estatística com aumento dos valores da hemoglobina e redução dos valores de reticulócitos, leucócitos e plaquetas. Não foram observados sinais ou sintomas sugestivos de toxicidade medicamentosa em ambos os grupos. O uso de hidroxiuréia em todos os pacientes parece ser seguro e eficaz e assegura melhora da qualidade de vida e benefícios a seus familiares. Ademais, as doses preconizadas de hidroxiuréia aparentemente não foram mielotóxicas, não tendo sido necessária a suspensão do tratamento em nenhum dos pacientes.
The use of hydroxyurea increases concentrations of fetalhemoglobin (Hb F) in sickle cell disease patients. It has beenused in adults and in trials with children with the aim of preventingevents such as episodes of pain or stokes. The objective of thisstudy was to analyze the efficacy and side effects of Hydroxyureain children with ages ranging from 5 to 17 years and also inyoung adults with SS or Sâ0 hemoglobinopathies. The patientswere treated in the outpatient clinic of the Hemope Hospital.Young patients were treated with hydroxyurea at 10 mg/kg/daywhich was increased by 5 mg/kg/day at 8-week intervals untilreaching a maximum dose of 25 mg/kg/day. For adults, thetreatment started at 500 mg/day and increased until a dose of1000 mg/day was reached. Total Hb F levels and the MeanCorpuscular Volume rose with hydroxyurea therapy and therewas a reduction of events involving pain as well as the necessityof hospitalization among the pediatric patients. With the over 18-year-old patients, a better clinical state was noticed together witha rise in hemoglobin levels and a reduction in the reticulocyte,leukocyte and platelet counts. No signs or symptoms in respect todrug toxicity were evidenced in either group. The use ofhydroxyurea seems to be safe and effective in both children andyoung adults with sickle cell disease. The drug also improves thequality of life of these patients and their families. Additionally, thedosages of hydroxyurea used in this group of patients did notcause any bone marrow toxicity or other side effects.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano de 80 o más Años , Preescolar , Niño , Anemia de Células Falciformes , Hemoglobina Fetal , Hidroxiurea/administración & dosificación , Hidroxiurea/uso terapéuticoAsunto(s)
Humanos , Seropositividad para VIH/tratamiento farmacológico , Retroviridae/efectos de los fármacos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adyuvantes Inmunológicos/administración & dosificación , Inmunoadhesinas CD4/administración & dosificación , Combinación de Medicamentos , Hidroxiurea/administración & dosificación , Complejo Mycobacterium avium/efectos de los fármacos , Nucleósidos/administración & dosificación , Inhibidores de Proteasas/administración & dosificación , Replicación Viral , Inhibidores de la Transcriptasa Inversa/administración & dosificaciónRESUMEN
The use of hydroxyurea (HU) can improve the clinical course of sickle cell disease. However, several features of HU treatment remain unclear, including the predictability of drug response and determination of adequate doses, considering positive responses and minimal side effects. In order to identify adequate doses of HU for treatment of sickle cell disease, 10 patients, 8 with sickle cell anemia and 2 with Sbeta thalassemia (8SS, 2SBeta), were studied for a period of 6 to 19 months in an open label dose escalation trial (10 to 20 mg kg(-1) day(-1)). Hemoglobin (Hb), fetal hemoglobin (Hb F) and mean corpuscular volume (MCV) values and reticulocyte, neutrophil and platelet counts were performed every two weeks during the increase of the HU dose and every 4 weeks when the maximum HU dose was established. Reduction in the number of vasoocclusive episodes was also considered in order to evaluate the efficiency of the treatment. The final Hb and Hb F concentrations, and MCV values were significantly higer than the initial values, while the final reticulocyte and neutrophil counts were significantly lower. There was an improvement in the concentration of Hb (range: 0.7-2.0 g/dl) at 15 mg HU kg(-1) day(-1), but this concentration did not increase significantly when the HU dose was raised to 20 mg kg(-1) day(-1). The concentration of Hb F increased significantly (range: 1.0-18.1 per cent) when 15 mg HU was used, and continued to increase when the dose was raised to 20 mg kg(-1) day (-1). The final MCV values increased 11-28 fl (femtoliters). However, reticulocyte (range: 51-205 x 10(9)/l) and neutrophil counts (range: 9.5-1.3 x 10(9)/l) obtained at this dose were significantly lower than those obtained with 15 mg kg(-1) day(-1). All patients reported a decrease in frequency or severity of vasoocclusive episodes. These results suggest that a hydroxyurea dose of 15 mg kg(-1) day(-1) seems to be adequate for treatment of sickle cell disease in view of the minimal side effects observed and the improvement in laboratory and clinical parameters.
Asunto(s)
Humanos , Anemia de Células Falciformes/tratamiento farmacológico , Hidroxiurea/administración & dosificación , Formas de Dosificación , Hidroxiurea/uso terapéutico , Talasemia/tratamiento farmacológicoRESUMEN
Se presenta el estudio de 9 pacientes que padecen psoriasis con serologia positiva para HIV.Entre tres de ellos la aparicion de la psoriasis fue previa al dignostico del HIV+, en los restantes posterior. Las formas clinicas de psoriasis halladas fueron: vulgar en tres, invertida en tres, pustulosa en dos y con compromiso de pequeños pliegues en uno. Los antecedentes familiares de psoriasis estuvieron presentes en uno, no se consignaron en dos y estuvieron ausentes en seis. El estadio clinico de la infeccion por HIV fue C3 en cinco, B2 en tres y en uno B3. La psoriasis se caracterizo por ser mas severa y, en dos casos, acompañada de sepsis estafilococcica. El tratamiento con medidas locales(cremas con corticoides, queratoliticos y balneoterapia) obtuvo resultados variables y la antibioticoterapia endovenosa instituida por la sepsis mejoro notablemente las lesiones cutaneas.