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1.
N Engl J Med ; 382(3): 233-243, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31940698

RESUMO

BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).


Assuntos
Eritropoetina/administração & dosagem , Lactente Extremamente Prematuro , Doenças do Prematuro/prevenção & controle , Transtornos do Neurodesenvolvimento/prevenção & controle , Encéfalo/diagnóstico por imagem , Pré-Escolar , Método Duplo-Cego , Eritropoetina/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/mortalidade , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Ultrassonografia
2.
Medicine (Baltimore) ; 99(2): e18577, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914036

RESUMO

BACKGROUND: Autologous blood transfusion helps to avoid or reduce the need for allogenic blood transfusion in patients undergoing major surgery. We examined the value of erythropoietin therapy to support preoperative autologous blood donation (PABD) in patients undergoing orthopedic surgery. METHODS: For this systematic review and meta-analysis, Medline, Cochrane, EMBASE, and Google Scholar databases were searched from October 26th, 1989 until September 30th, 2017. Primary outcomes were percentages of patients able to donate ≥4 units of blood for autologous transfusion, amount of allogeneic blood transfused, changes in hematocrit and hemoglobin levels from before PABD to immediately before surgery, and adverse events. RESULTS: Of 256 studies identified, 18 studies met the inclusion criteria with a total of 1914 patients (mean age 51-69 years), of whom 1153 were treated with erythropoietin. Erythropoietin was associated with a greater percentage of patients able to donate ≥4 units of blood for autologous use compared to controls (OR = 6.00, 95% CI = 3.97 to 9.09, P < .001). Patients receiving preoperative erythropoietin had significantly less of a reduction in hematocrit and hemoglobin levels from before PABD to immediately before surgery compared with controls (hematocrit: mean differences = -1.438, 95% CI = -2.14 to -0.73, P < .001; hemoglobin: mean differences = -1.426, 95% CI = -1.78 to -1.07, P < .001). No significant differences were observed in the amount of allogenic blood transfused between patients receiving erythropoietin and controls (difference in means = -0.220, 95% CI = -0.536 to 0.097, P = .174). Patients who received erythropoietin were less likely to experience dizziness than controls, but the incidence of nausea or fatigue were similar between groups. CONCLUSION: Erythropoietin therapy during the PABD period results in less of a reduction in hematocrit and hemoglobin levels and an increase in the percentage of patients able to donate blood preoperatively.


Assuntos
Transfusão de Sangue Autóloga/métodos , Eritropoetina/uso terapêutico , Procedimentos Ortopédicos/métodos , Período Pré-Operatório , Idoso , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Feminino , Hematócrito , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Early Hum Dev ; 137: 104831, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31374455

RESUMO

Erythropoietin treatment is associated with a reduction in moderate to severe bronchopulmonary dysplasia in preterm infants. A regional retrospective study. OBJECTIVE: To determine whether premature infants treated with erythropoietin (Epo) in the neonatal period for anemia had a lower incidence of bronchopulmonary dysplasia (BPD), defined as oxygen need at 36 weeks postmenstrual age, and lower rehospitalization rates in the first year of life than infants not exposed. METHODS: Retrospective study of a population of infants born at 23 to 32 weeks gestational age, between January 2009 and December 2014, with birthweight ≤1500 g. Patient characteristics, and risk factors for BPD were compared between patients who received erythropoietin, and those not exposed. To examine the association between the outcomes of BPD at 36 weeks PMA, rehospitalization, and erythropoietin treatment, we performed a propensity score (PS) analysis using inverse probability of treatment weighted (IPTW) approach. For comparison, we conducted a logistic regression adjusting for the same covariates used to generate PS using the original population. RESULTS: The study population included 1821 preterm infants: 928 received Epo and 893 did not. Epo treatment was associated with a reduction in BPD (18.8% versus 25.9%, p < 0.01) at 36 weeks PMA and reduced median length of stay with lowest BPD rate with Epo initiation before 2 weeks of age. There was no difference in rehospitalization rates in the first year of life. CONCLUSION: Erythropoietin treatment was associated with a reduction in BPD but not in rehospitalization rate in the first year of life.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Eritropoetina/uso terapêutico , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Internação/estatística & dados numéricos , Masculino , Readmissão do Paciente/estatística & dados numéricos
4.
Neonatology ; 115(4): 406-410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30974429

RESUMO

Currently the question of whether to maintain a higher hemoglobin level by transfusing more liberally, as opposed to a more restrictive strategy with lower hemoglobin maintenance levels, has not been answered. We review summarized conclusions of a Cochrane systematic review and meta-analysis of 614 infants in 4 randomized controlled trials (RCT) pooling data. This suggests potential benefits of higher hemoglobin levels, i.e., a possible improved cognition of infants at 18-21 months' corrected age and a reduction of apnea. However, the data on cognition is hypothesis generating as it derives from a post hoc analysis from a single trial in 451 infants. Moreover, the data on apnea need confirmation in larger trials. The effect of adding data of cognitive 2-year outcomes of 1,744 infants from 2 RCT, which will be reported soon, should expand our understanding. This new data will need to be integrated with the older generation of RCTs but also with emerging suggestions from observational data on potential risks of blood transfusions. We discuss some of these warnings from observational studies. Finally, we ask whether we are ready to individualize blood transfusion to physiological measures made in individual infants, and we point to some current difficulties hindering this step.


Assuntos
Anemia Neonatal/prevenção & controle , Transfusão de Eritrócitos/tendências , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido Prematuro/sangue , Anemia Neonatal/sangue , Apneia/prevenção & controle , Eritropoetina/efeitos adversos , Eritropoetina/sangue , Prática Clínica Baseada em Evidências , Humanos , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto , Retinopatia da Prematuridade/etiologia
5.
Medicine (Baltimore) ; 98(10): e14789, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30855492

RESUMO

RATIONALE: Thymoma is a type of rare tumor in the thymus gland, and among patients with thymoma, less than 10% will develop pure red cell aplasia (PRCA), whereas less than 5% of patients with PRCA have a thymoma. The optimal approach for PRCA in thymoma is immunosuppressive therapy, such as steroids, cyclosporine, and human antithymocyte globulin. PATIENT CONCERNS: A sixty-one-year-old male was diagnosed with thymoma with PRCA after he complained fatigue, tinnitus, and weakness for 1 month, he received therapy with recombinant erythropoietin (rhEPO) for 1 month after the tumor was totally resected and readmitted with pulmonary embolism and received anticoagulation therapy with enoxaparin for 3 months. DIAGNOSES: Thymoma, pure red cell aplasia, pulmonary embolism. INTERVENTION: He received cyclosporine A, prednisone and rhEPO treatment. Two months after the thymectomy and postoperative radiation, he was readmitted with pulmonary embolism. OUTCOMES: Thymoma and pulmonary embolism become complete response (CR), PRCA become partial response (PR). LESSONS: Clinicians should be alert to the possibility of the increased risk of thrombosis induced by rhEPO when it used to treat PRCA associated with thymoma. If other medication is effective for managing PRCA, rhEPO should be avoided.


Assuntos
Eritropoetina/efeitos adversos , Fármacos Hematológicos/efeitos adversos , Embolia Pulmonar/etiologia , Aplasia Pura de Série Vermelha/tratamento farmacológico , Timoma/complicações , Neoplasias do Timo/complicações , Eritropoetina/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/patologia , Embolia Pulmonar/terapia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Timoma/terapia , Neoplasias do Timo/terapia
6.
BMC Pediatr ; 19(1): 13, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621649

RESUMO

BACKGROUND: Although therapeutic hypothermia improves the outcome of neonatal hypoxic-ischemic encephalopathy (HIE), its efficacy is still limited. This preliminary study evaluates the safety and feasibility of the combination therapy with erythropoietin (Epo), magnesium sulfate and hypothermia in neonates with HIE. METHODS: A combination therapy with Epo (300 U/kg every other day for 2 weeks), magnesium sulfate (250 mg/kg for 3 days) and hypothermia was started within 6 h of birth in neonates who met the institutional criteria for hypothermia therapy. All patients received continuous infusion of dopamine. Vital signs and adverse events were recorded during the therapy. Short-term and long-term developmental outcomes were also evaluated. RESULTS: Nine patients were included in the study. The mean age at first intervention was 3.9 h (SD, 0.5). Death, serious adverse events or changes in vital signs likely due to intervention were not observed during hospital care. All nine patients completed the therapy. At the time of hospital discharge, eight patients had established oral feeding and did not require ventilation support. Two patients had abnormal MRI findings. At 18 months of age, eight patients received a follow-up evaluation, and three of them showed signs of severe neurodevelopmental disability. CONCLUSION: The combination therapy with 300 U/kg Epo every other day for 2 weeks, 250 mg/kg magnesium sulphate for 3 days and therapeutic hypothermia is feasible in newborn patients with HIE. TRIAL REGISTRATION: ISRCTN33604417 retrospectively registered on 14 September 2018.


Assuntos
Eritropoetina/administração & dosagem , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Sulfato de Magnésio/administração & dosagem , Terapia Combinada , Esquema de Medicação , Eritropoetina/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Hipotermia Induzida/efeitos adversos , Recém-Nascido , Sulfato de Magnésio/efeitos adversos , Masculino , Projetos Piloto , Estudos Prospectivos
7.
Clin Exp Nephrol ; 23(3): 349-361, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30291472

RESUMO

BACKGROUND: Previous randomized-controlled trials have shown that targeting higher hemoglobin (Hb) levels using high dose of ESA in non-dialysis chronic kidney disease (NDCKD) patients resulted in poorer cardiovascular outcome; however, it remains unknown how high Hb levels achieved by ESA in clinical practice dose could affect renal outcome. METHODS: In a multicenter prospective observational study, Japanese NDCKD patients with an estimated glomerular filtration rate (eGFR) of ≥ 6 mL/min/1.73 m2 and renal anemia (Hb < 11 g/dL) treated with epoetin beta pegol (C.E.R.A.) for the first time were divided into two groups by Hb level (< 11 g/dL or ≥ 11 g/dL) in Week 12 of C.E.R.A. treatment (Week 12 Hb). Renal outcome was defined as time until the first occurrence of one of the following: progression to renal replacement therapy, serum creatinine doubling, or eGFR falling below 6 mL/min/1.73 m2. The effect of Week 12 Hb on the onset of renal events was assessed by the Kaplan-Meier and multivariate Cox regression analyses. RESULTS: In the landmark analysis which included 2851 patients, Kaplan-Meier renal survival rate was 37.57% in the < 11 g/dL group and was significantly higher (51.47%) in the ≥ 11 g/dL group (P < 0.0001). Multivariate Cox regression analysis revealed significantly higher risk of renal events in the < 11 g/dL group than in the ≥ 11 g/dL group (hazard ratio: 1.26; 95% confidence interval: 1.05-1.51; P = 0.0103). CONCLUSIONS: The results suggest that week 12 Hb levels ≥ 11 g/dL achieved with C.E.R.A. treatment were associated with better renal outcomes than Hb levels < 11 g/dL.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/uso terapêutico , Hemoglobinas/análise , Falência Renal Crônica/mortalidade , Polietilenoglicóis/uso terapêutico , Insuficiência Renal Crônica/sangue , Idoso , Idoso de 80 Anos ou mais , Eritropoetina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/complicações
8.
Drug Test Anal ; 11(1): 8-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30488582

RESUMO

A number of high profile revelations concerning anti-doping rule violations over the past 12 months have outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti-doping system. At this time, the necessity to enhance, expand, and improve analytical test methods in response to the substances outlined in the World Anti-Doping Agency (WADA) Prohibited List represents an increasingly crucial task for modern sports drug testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug testing assays, drug elimination profiles, and alternative sample matrices, together with recent advances in instrumental developments. This annual banned-substance review evaluates literature published between October 2017 and September 2018 offering an in-depth evaluation of developments in these arenas and their potential application to substances reported in WADA's 2018 Prohibited List.


Assuntos
Doping nos Esportes/prevenção & controle , Substâncias para Melhoria do Desempenho/análise , Detecção do Abuso de Substâncias/métodos , Anabolizantes/efeitos adversos , Anabolizantes/análise , Ansiolíticos/efeitos adversos , Ansiolíticos/análise , Doping nos Esportes/tendências , Eritropoetina/efeitos adversos , Eritropoetina/análise , Humanos , Substâncias para Melhoria do Desempenho/efeitos adversos , Esportes/normas , Esportes/tendências , Detecção do Abuso de Substâncias/tendências
9.
Clin Exp Nephrol ; 23(4): 501-512, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30406500

RESUMO

BACKGROUND: Vascular calcification is common in chronic kidney disease (CKD) patients, while erythropoietin (EPO) is widely used in the treatment of renal anemia in CKD patients, whether there is a link between the two is still not clear. METHODS: The primary rat vascular smooth muscle cells (VSMCs) and CKD rats were treated with EPO and the calcium deposition was observed by alizarin red staining, von Kossa staining and calcium quantification. Activation of JAK2/STAT3/BMP-2 axis and NF-κB signaling pathways was investigated by Western blotting. RESULTS: EPO-induced calcium deposition in VSMCs and significantly potentiated calcification in CKD rats. Furthermore, EPO activated JAK2/STAT3/BMP-2 axis, NF-κB pathway and the pro-calcification effect of EPO was partially blocked by the STAT3 inhibitor (Cryptotanshinone) or NF-κB inhibitor (BAY 11-7082), respectively, in vitro. CONCLUSION: EPO could promote VSMCs calcification in vitro and in vivo and this effect may be achieved through the JAK2/STAT3/BMP-2 axis and NF-κB pathway.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Eritropoetina/farmacologia , Janus Quinase 2/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Calcificação Vascular/induzido quimicamente , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Anemia/tratamento farmacológico , Anemia/etiologia , Animais , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Eritropoetina/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Masculino , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso , NF-kappa B/antagonistas & inibidores , Nitrilos/farmacologia , Fenantrenos/farmacologia , Fosforilação , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/complicações , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Regulação para Cima/efeitos dos fármacos
10.
J Bras Nefrol ; 41(1): 145-151, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30160771

RESUMO

INTRODUCTION: Anemia is a frequent multifactorial complication of CKD seen in patients on dialysis derived mainly from impaired erythropoietin (EPO) production. A less common cause of anemia in individuals with CKD is pure red cell aplasia (PRCA) secondary to the production of anti-EPO antibodies. OBJECTIVE: This paper aimed two describe two cases of PRCA secondary to the production of anti-EPO antibodies including choice of treatment, patient progression, and a literature review. MATERIALS: This study included the cases of two patients with CKD on hemodialysis with severe anemia in need of specific investigation and management. RESULTS: Patient 1 with CKD secondary to hypertension treated with EPO for 7 months showed persistent decreases in hemoglobin (Hb) levels despite the subcutaneous administration of increasing doses of EPO; the patient required recurring blood transfusions. Workup and imaging tests were negative for the main causes of anemia in individuals with CKD on dialysis. Patient 2 with CKD secondary to adult polycystic kidney disease had been taking EPO for 2 years. The patient developed severe abrupt anemia the month he was started on HD, and required recurring transfusions to treat the symptoms of anemia. Workup and imaging findings were inconclusive. Specific laboratory tests confirmed the patients had anti-EPO antibodies. After six months of immunosuppressant therapy (corticosteroids + cyclosporine) the patients were stable with Hb > 9.0 g/dl. CONCLUSION: PRCA is a rare condition among patients on dialysis treated with rhEPO and should be considered as a possible cause of refractory anemia. Treating patients with PRCA may be challenging, since the specific management and diagnostic procedures needed in this condition are not always readily available.


Assuntos
Anticorpos Neutralizantes/sangue , Eritropoetina/imunologia , Eritropoetina/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Aplasia Pura de Série Vermelha/etiologia , Diálise Renal/efeitos adversos , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Eritropoetina/efeitos adversos , Eritropoetina/síntese química , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Transplante de Rim , Masculino , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Aplasia Pura de Série Vermelha/tratamento farmacológico , Resultado do Tratamento
11.
Physiol Rep ; 6(24): e13924, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30592183

RESUMO

Recombinant human erythropoietin (rHuEPO) has been used as a performance-enhancing agent by athletes in a variety of sports. The resulting increase in hematocrit levels leads to increased blood viscosity and can affect blood flow, potentially increasing the athlete's risk of developing health complications. However, the actual effects of using rHuEPO on microvascular blood flow and post-occlusive reactive hyperemia are currently unknown. We therefore evaluated the effect of rHuEPO on the cutaneous microcirculation in well-trained cyclists using laser speckle contrast imaging (LSCI). This study was part of a randomized, double-blind, placebo-controlled, parallel trial designed to investigate the effects of rHuEPO in 47 well-trained adult cyclists (age 18-50 years). Subjects received a weekly dose of either rHuEPO or placebo for 8 weeks, and LSCI was performed at baseline, after a maximal exercise test in week 6, and before maximal exercise in week 8. Endpoints included basal blood flux, maximum post-occlusion reperfusion, and time to return to baseline. Despite an increase in hematocrit levels in the rHuEPO-treated group, we found no statistically significant difference in microvascular function measured between the rHuEPO-treated group and the placebo group. Our results suggest that the increased hematocrit levels in rHuEPO-treated well-trained cyclists are not associated with changes in microvascular blood flow or post-occlusive reactive hyperemia measured using LSCI.


Assuntos
Eritropoetina/farmacologia , Exercício , Hiperemia/etiologia , Microcirculação/efeitos dos fármacos , Adulto , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Pele/irrigação sanguínea
13.
Am J Nephrol ; 48(4): 251-259, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253403

RESUMO

BACKGROUND: Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III study aimed to compare the efficacy and safety of CinnaPoietin® (epoetin beta, CinnaGen) with Eprex® (epoetin alfa, Janssen Cilag) in the treatment of anemia in ESRD hemodialysis patients. METHODS: In this randomized, active-controlled, double-blind, parallel, and non-inferiority trial, patients were randomized to receive either CinnaPoietin® or Eprex® for a 26-week period. The primary endpoints of this study were to assess the mean hemoglobin (Hb) change during the last 4 weeks of treatment from baseline along with the evaluation of the mean weekly epoetin dosage per kilogram of body weight that was necessary to maintain the Hb level within 10-12 g/dL during the last 4 weeks of treatment. As the secondary objective, safety was assessed along with other efficacy endpoints. RESULTS: A total of 156 patients were included in this clinical trial. There was no statistically significant difference between treatment groups regarding the mean Hb change (p = 0.21). In addition, the mean weekly epoetin dosage per kg of body weight for maintaining the Hb level within 10-12 g/dL showed no statistically significant difference between treatment arms (p = 0.63). Moreover, both products had comparable safety profiles. However, the incidence of Hb levels above 13 g/dL was significantly lower in the CinnaPoietin® group. CONCLUSION: CinnaPoietin® was proved to be non-inferior to Eprex® in the treatment of anemia in ESRD hemodialysis patients. The trial was registered in Clinicaltrials.gov (NCT03408639).


Assuntos
Anemia/tratamento farmacológico , Epoetina alfa/administração & dosagem , Eritropoetina/administração & dosagem , Hematínicos/administração & dosagem , Falência Renal Crônica/complicações , Adulto , Idoso , Anemia/sangue , Anemia/etiologia , Epoetina alfa/efeitos adversos , Eritropoetina/efeitos adversos , Feminino , Hematínicos/efeitos adversos , Hemoglobinas/análise , Humanos , Injeções Subcutâneas , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Diálise Renal , Resultado do Tratamento
14.
Auton Neurosci ; 215: 28-36, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29753556

RESUMO

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach.


Assuntos
Antidiuréticos/uso terapêutico , Fármacos do Sistema Nervoso Autônomo/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Eritropoetina/uso terapêutico , Síndrome da Taquicardia Postural Ortostática/tratamento farmacológico , Solução Salina/uso terapêutico , Cloreto de Sódio/uso terapêutico , Antidiuréticos/efeitos adversos , Fármacos do Sistema Nervoso Autônomo/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Eritropoetina/efeitos adversos , Humanos , Solução Salina/administração & dosagem , Solução Salina/efeitos adversos , Cloreto de Sódio/efeitos adversos
15.
Nefrologia ; 38(2): 136-140, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29409679

RESUMO

Posterior reversible encephalopathy syndrome is a clinical and radiological entity with acute or subacute neurological presentation associated with brain lesions that primarily affect the white matter of the posterior regions. It is often associated with the rapid onset of severe hypertension and/or with kidney failure (acute and chronic), but it has also been reported as a neurological complication in several medical conditions. In recent years, there has been an increase in the number of cases and related publications due to the advance of diagnostic imaging techniques. The characteristic radiological finding includes hyperintense lesions in T2- and FLAIR-weighted magnetic resonance imaging, which are often bilateral and located in the posterior cerebral regions and correspond to areas of vasogenic oedema. Little is known about the pathophysiology of posterior reversible encephalopathy syndrome. The most accepted theory, especially in cases with associated hypertension, is the loss of cerebral self-regulation which leads to the onset of vasogenic oedema. The main feature of this syndrome is the reversibility of both symptoms and cerebral lesions with an early and appropriate diagnosis. Despite the frequent association with kidney failure and severe hypertension, there are few cases reported in patients on peritoneal dialysis. This article presents a review of PRES in peritoneal dialysis patients in the published literature.


Assuntos
Diálise Peritoneal , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Fatores Etários , Anti-Hipertensivos/uso terapêutico , Volume Sanguíneo , Causalidade , Diagnóstico Diferencial , Eritropoetina/efeitos adversos , Eritropoetina/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Imagem por Ressonância Magnética , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/etiologia , Síndrome da Leucoencefalopatia Posterior/prevenção & controle , Fatores de Risco
16.
Mol Cell Endocrinol ; 464: 75-87, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28119134

RESUMO

Erythropoietin (EPO) is the main hormone regulating red blood cell (RBC) production. The large-scale production of a recombinant human erythropoietin (rHuEPO) by biotechnological methods has made possible its widespread therapeutic use as well as its misuse in sports. Since the marketing of the first epoetin in 1989, the development has progressed to the third-generation analogs. However, the production of rHuEPO is costly, and the frequent administration of an injectable formula is not optimal for compliance of therapeutic patients. Hence, pharmaceutical industries are currently developing alternative approaches to stimulate erythropoiesis, which might offer new candidates for doping purposes. The hypoxia inducible factors (HIF) pathway is of particular interest. The introduction of new erythropoiesis-stimulating agents (ESAs) for clinical use requires subsequent development of anti-doping methods for detecting the abuse of these substances. The detection of ESAs is based on two different approaches, namely, the direct detection of exogenous substances and the indirect detection, for which the effects of the substances on specific biomarkers are monitored. Omics technologies, such as ironomics or transcriptomics, are useful for the development of new promising biomarkers for the detection of ESAs. Finally, the illicit use of ESAs associates with multiple health risks that can be irreversible, and an essential facet of anti-doping work is to educate athletes of these risks. The aim of this review is to provide an overview of the evolution of ESAs, the research and implementation of the available detection methods, and the side effects associated with the misuse of ESAs.


Assuntos
Eritropoetina/efeitos adversos , Eritropoetina/análise , Substâncias para Melhoria do Desempenho/efeitos adversos , Substâncias para Melhoria do Desempenho/análise , Doping nos Esportes , Eritropoetina/farmacologia , Humanos , Substâncias para Melhoria do Desempenho/farmacologia , Transcriptoma/genética
17.
Clin J Am Soc Nephrol ; 13(1): 81-90, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-29097481

RESUMO

BACKGROUND AND OBJECTIVES: The study was conducted to identify a conversion factor for switching from previous erythropoiesis-stimulating agents (ESAs) to continuous erythropoietin receptor activator-methoxy polyethylene glycol-epoetin beta (C.E.R.A.) and to document the efficacy and long-term safety of C.E.R.A. in pediatric patients with anemia of CKD undergoing hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this open-label, multicenter study, patients aged 6-17 years, with stable chronic anemia of CKD, undergoing hemodialysis received C.E.R.A. every 4 weeks, at a starting dose determined by previous weekly epoetin alfa/beta or darbepoetin dosing. After a 16-week dose-titration and a 4-week evaluation period, patients with stable hemoglobin could enter a 1-year optional safety extension. RESULTS: A total of 64 patients were enrolled. A conversion factor (4 µg every 4 weeks for each weekly dose of 125 IU epoetin alfa/beta or 0.55 µg darbepoetin) was identified that allowed patients to maintain hemoglobin within target levels on switching to C.E.R.A. from another ESA. Using this conversion factor, the adjusted mean change in hemoglobin from baseline to evaluation was -0.09 g/dl (95% confidence interval, -0.45 to 0.26); 81% of patients maintained hemoglobin within 10.0-12.0 g/dl and 75% maintained hemoglobin within 1.0 g/dl of baseline. Results were consistent across age groups (6-11 and 12-17 years) and previous ESA. Thirty-seven patients entered the safety extension period and 17 completed 73 weeks of treatment. Most withdrawals were for kidney transplantation. A total of 70% of patients had hemoglobin within 10.0-12.0 g/dl at last observation, and 62% were within ±1.0 g/dl of baseline. Safety was similar to studies in adult patients, with no new signal detected. CONCLUSIONS: Using a defined conversion factor, 4-weekly C.E.R.A. was efficacious in maintaining hemoglobin levels in pediatric patients with stable anemia of CKD undergoing hemodialysis, switching from maintenance treatment with epoetin alfa/beta or darbepoetin. Safety was consistent with the known C.E.R.A. safety profile in adults.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/administração & dosagem , Hematínicos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Diálise Renal , Insuficiência Renal Crônica/terapia , Adolescente , Fatores Etários , Anemia/sangue , Anemia/diagnóstico , Anemia/etiologia , Biomarcadores/sangue , Criança , Esquema de Medicação , Substituição de Medicamentos , Eritropoetina/efeitos adversos , Feminino , Hematínicos/efeitos adversos , Hemoglobinas/metabolismo , Humanos , Masculino , Polietilenoglicóis/efeitos adversos , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do Tratamento
18.
Blood Transfus ; 16(1): 53-62, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27893353

RESUMO

BACKGROUND: Jehovah's Witnesses who refuse blood transfusion have high mortality. Erythropoietin (EPO) has been used as an alternative to blood transfusion. The optimal dosing of EPO in anaemic Jehovah's Witnesses is unknown. The aim of our study was to evaluate the clinical benefits of treatment with a low dose (<600 IU/kg/week) of epoietin beta (EPO-ß). MATERIALS AND METHODS: This was an observational study, retrospectively considering a 10-year period during which 3,529 adult Jehovah's Witnesses with a total of 10,786 hospital admissions were identified from databases of four major public hospitals in New Zealand. Patients with severe symptomatic anaemia (haemoglobin <80 g/L) who were unable to tolerate physical activity were included in the study. Patients treated without EPO were assigned to the conventional therapy group and those treated with EPO to the EPO treatment group. RESULTS: Ninety-one Jehovah's Witnesses met the eligibility criteria. Propensity score matching yielded a total of 57 patients. Patients treated with conventional therapy and those treated with EPO had similar durations of severe anaemia (average difference 6.25 days, 95% confidence interval [CI]: -3.77-16.27 days; p=0.221). The mortality rate among Jehovah's Witnesses treated with conventional therapy was 4.68 per year (95% CI: 2.23-9.82), while that in those treated with EPO was 2.77 per year (95% CI: 0.89-8.60). Treatment with EPO was associated with a mortality ratio of 0.59 (95% CI: 0.1-2.6; p=0.236). Both groups of patients had similar in-hospital survival (p=0.703). DISCUSSION: Treatment with low-dose EPO-ß was not associated with either shorter duration of severe anaemia or a reduction in mortality.


Assuntos
Anemia/tratamento farmacológico , Bases de Dados Factuais , Eritropoetina/administração & dosagem , Testemunhas de Jeová , Adulto , Idoso , Anemia/sangue , Anemia/mortalidade , Intervalo Livre de Doença , Eritropoetina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
19.
Clin Pharmacol Ther ; 103(2): 296-303, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28913827

RESUMO

Concerns have been expressed that large numbers of nonvalue-added reports have been accumulating in adverse drug reaction (ADR) databases, for example, via patient support programs. We performed an assessment of the impact of such reports, which we refer to as "precautionary reports," on safety signal detection in the Netherlands. The case narratives of ADR reports of three case products were screened with text-mining algorithms to identify those reports that lack a causal relationship with the suspected medicinal product. We demonstrate that precautionary reports impede the optimal use of the pharmacovigilance system by, on the one hand, masking safety signals and, on the other hand, creating spurious signals. The precautionary reporting bias and its suppressing effect on statistical signal detection results in an altered adverse event safety profile. The findings from this study highlight the need for a better alignment between regulatory authorities and marketing authorization holders regarding pharmacovigilance guidelines.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Mineração de Dados/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicina Baseada em Evidências/métodos , Pesquisa Médica Translacional/métodos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Algoritmos , Animais , Viés , Mineração de Dados/estatística & dados numéricos , Bases de Dados Factuais , Difosfonatos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Antagonistas dos Receptores de Endotelina/efeitos adversos , Eritropoetina/efeitos adversos , Medicina Baseada em Evidências/estatística & dados numéricos , Humanos , Modelos Animais , Modelos Teóricos , Países Baixos , Segurança do Paciente , Reprodutibilidade dos Testes , Medição de Risco , Pesquisa Médica Translacional/estatística & dados numéricos
20.
Blood Purif ; 45(1-3): 139-146, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30959500

RESUMO

Hyporesponsiveness to erythropoietin stimulating agents (ESAs) is a condition associated with increased mortality. Even after identifying the condition, the causes are difficult to treat and only partially reversible in end-stage renal disease patients. Thus, the role of more recent hemodialysis (HD) techniques in improving such conditions is an emerging issue. However, major randomized clinical trials have not confirmed the results of smaller observational studies in which online hemodiafiltration has shown some efficacy in improving patients' response to ESAs. In our interpretation, these findings are not in contrast, but they can be explained by a better understanding of the interactions between HD and ESAs on iron mobilization, first of all through the role of hepcidin. The kinetics of hepcidin removal through HD combined with the action of selected ESAs may help the clinician in prescribing the best association between HD treatment and ESAs to overcome hyporesponsiveness.


Assuntos
Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Hemodiafiltração , Hepcidinas/sangue , Ferro/sangue , Eritropoetina/efeitos adversos , Hematínicos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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