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3.
BMC Cancer ; 19(1): 792, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399079

RESUMO

BACKGROUND: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy. Clinical practice guidelines recommend routine prophylactic coverage with granulocyte colony-stimulating factor (G-CSF)-such as pegfilgrastim-for most patients receiving chemotherapy with an intermediate to high risk for FN. Patterns of pegfilgrastim prophylaxis during the chemotherapy course and associated FN risks in US clinical practice have not been well characterized. METHODS: A retrospective cohort design and data from two commercial healthcare claims repositories (01/2010-03/2016) and Medicare Claims Research Identifiable Files (01/2007-09/2015) were employed. Study population included patients who had non-metastatic breast cancer or non-Hodgkin's lymphoma and received intermediate/high-risk regimens. Pegfilgrastim prophylaxis use and FN incidence were ascertained in each chemotherapy cycle, and all cycles were pooled for analyses. Adjusted odds ratios for FN were estimated for patients who did versus did not receive pegfilgrastim prophylaxis in that cycle. RESULTS: Study population included 50,778 commercial patients who received 190,622 cycles of chemotherapy and 71,037 Medicare patients who received 271,944 cycles. In cycle 1, 33% of commercial patients and 28% of Medicare patients did not receive pegfilgrastim prophylaxis, and adjusted odds of FN were 2.6 (95% CI 2.3-2.8) and 1.6 (1.5-1.7), respectively, versus those who received pegfilgrastim prophylaxis. In cycle 2, 28% (commercial) and 26% (Medicare) did not receive pegfilgrastim prophylaxis; corresponding adjusted FN odds were comparably elevated (1.9 [1.6-2.2] and 1.6 [1.5-1.8]). Results in subsequent cycles were similar. Across all cycles, 15% of commercial patients and 23% of Medicare patients did not receive pegfilgrastim prophylaxis despite having FN in a prior cycle, and prior FN increased odds of subsequent FN by 2.1-2.4 times. CONCLUSIONS: Notwithstanding clinical practice guidelines, a large minority of patients did not receive G-CSF prophylaxis, and FN incidence was substantially higher among this subset of the population. Appropriate use of pegfilgrastim prophylaxis may reduce patient exposure to this potentially fatal but largely preventable complication of myelosuppressive chemotherapy.


Assuntos
Quimioprevenção , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Padrões de Prática Médica , Idoso , Quimioprevenção/métodos , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Gerenciamento Clínico , Feminino , Filgrastim/administração & dosagem , Filgrastim/efeitos adversos , Fármacos Hematológicos/administração & dosagem , Fármacos Hematológicos/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Estudos Retrospectivos , Risco , Estados Unidos/epidemiologia
4.
Int J Clin Pract ; 73(11): e13404, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31408256

RESUMO

BACKGROUND: Patients undergoing chemotherapy are at risk of toxicity, especially of haematological origin. Granulocyte depletion, although often underestimated, can lead to the occurrence of an event defined as febrile neutropenia (FN). Neutropenic fever syndromes are dangerous because they cause major complications in around 25%-30% of patients and have a mortality rate of up to 11%. Treatment for FN was limited to antibiotics and supportive therapies until filgrastim was approved for use in the 1990s. OBJECTIVES: The present systematic review focuses on the efficacy and safety of this haematopoietic growth factor. DATA SOURCES AND METHODS: For this review, a systematic literature search of electronic databases and references from recent reviews up to December 2018 was carried out to identify clinical trials, observational studies and case reports evaluating filgrastim efficacy and safety. English language was defined as a restriction. Published randomised controlled trials (RCTs), case reports and reviews analysing the effects of filgrastim on severe neutropenia and its limits were considered. Four review authors independently selected the studies, assessed the risk of bias and extracted study data. RESULTS: As reported in ASCO guidelines, the efficacy of filgrastim with respect to placebo or no treatment in RCTs is based on its prevention of FN. A recent meta-analysis analysed nine RCTs with 2197 patients, revealing a reduction in the incidence of FN with filgrastim (risk ratio [RR] 0.63, 95% CI 0.53-0.75). These findings were further confirmed in two observational studies. Bone pain is the most commonly reported adverse event with filgrastim, while other toxicities are associated with filgrastim efficacy and with an increased neutrophil count. KEY FINDINGS: In conclusion, our findings attest to the previous results on the efficacy and safety of filgrastim.


Assuntos
Filgrastim/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Neutropenia/prevenção & controle , Antibacterianos/uso terapêutico , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
J Coll Physicians Surg Pak ; 29(8): 706-709, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31358087

RESUMO

OBJECTIVE: To assess the role of granulocyte-colony stimulating factor (G-CSF) for improving neutropenia in burns patients with neutropenia. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Jinnah Burn and Reconstructive Surgery Centre, Lahore, from May to October 2017. METHODOLOGY: Patients with burn injury, having absolute neutrophil count (ANC) <500 / µL or where it was expected to decrease to <500/µL within the next 48 hours, were recruited in the study. A detailed demographic profile of patients was taken, burn site was evaluated, and sample collection by phlebotomy was done in the complete blood count (CBC) vial. Samples were run in a CBC analyser and verification of neutrophil count on the neubuar chamber was done. ANC was taken for 3 days for each patient. Injection Filgrastim was given 300 µg subcutaneous (S/C) or intravenous (I/V) once daily until the neutropenia improved. Improvement was categorised as good, moderate and poor, depending on the number of days for improvement in ANC. The response was further stratified on the basis of age, gender and percentage of burn. RESULTS: A total of 39 patients with mean age of 32.1±14.4 years included 84.6% (n=33) males and 15.4% (n=6) females. Mean percentage of burn was 40.5±15.7%. In 12-40 years of age, there were 30/39 (76.9%) patients. Among them, 11/30 (36.6%) were good, 13/30 (43.3%) were moderate, and 6/30 (20%) were poor responders. In 41-70 years of age, there were 9/39 (23.1%) patients. Among them, 2/9 (22.2%) were good, 4/9 (44.44%) were moderate, and 3/9 (33.3%) were poor responders (p = 0.616). CONCLUSION: The addition of G-CSF injections to the standard treatment of burn injury markedly improve the neutrophil counts in burn patients with neutropenia.


Assuntos
Queimaduras/tratamento farmacológico , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Neutropenia/tratamento farmacológico , Adulto , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino
6.
BioDrugs ; 33(4): 373-389, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31161461

RESUMO

BACKGROUND: Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar). OBJECTIVE: The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology. METHODS: We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence. RESULTS: We identified 28 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 9 cohort studies (total N = 23,043) of G-CSF biosimilars [corrected]. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses. CONCLUSION: Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.


Assuntos
Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Anemia/induzido quimicamente , Neutropenia Febril Induzida por Quimioterapia/etiologia , Epoetina alfa/uso terapêutico , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
Ann Hematol ; 98(8): 1813-1826, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31098739

RESUMO

Pregnant patients with ß-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E'jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with ß- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15 g CCA powder for 4 weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects' peripheral blood before and after treatment. We found that ß CD 41-42(-TTCT)/ßA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype ß CD 41-42(-TTCT)/ßA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with ß-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.


Assuntos
Gelatina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Fármacos Hematológicos/uso terapêutico , Medicina Tradicional Chinesa/métodos , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Talassemia beta/tratamento farmacológico , Administração Oral , Adulto , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas Nucleares/agonistas , Proteínas Nucleares/metabolismo , Gravidez , Proteômica/métodos , Proteínas Repressoras/agonistas , Proteínas Repressoras/metabolismo , Transdução de Sinais , Espectrina/genética , Espectrina/metabolismo , Transcriptoma/efeitos dos fármacos , Talassemia beta/genética , Talassemia beta/metabolismo , Talassemia beta/patologia
8.
J Stroke Cerebrovasc Dis ; 28(8): e110-e112, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31126786

RESUMO

Polycythemia vera is a chronic myeloproliferative neoplasm, which is primarily characterized by elevated erythrocyte count with the risk of thrombosis, hemorrhage, and vasomotor symptoms. More common reported about bleeding events are gastrointestinal, mucosal, and cutaneous bleeding. Spontaneous cerebral hemorrhage/bleeding is seldom reported. Here, we report the case of a 50-year-old female with polycythemia vera who developed a spontaneous cerebral hemorrhage. She improved significantly after hydroxyurea agent and red cell apheresis, and the hematocrit decreased from 74% to 40%.


Assuntos
Hemorragia Cerebral/etiologia , Policitemia Vera/complicações , Biópsia , Remoção de Componentes Sanguíneos/métodos , Exame de Medula Óssea , Angiografia Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Feminino , Hematócrito , Fármacos Hematológicos/uso terapêutico , Humanos , Hidroxiureia/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Policitemia Vera/sangue , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Resultado do Tratamento
9.
Eur J Cancer Care (Engl) ; 28(4): e13034, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968997

RESUMO

OBJECTIVE: Real-world evidence data on the use of granulocyte colony-stimulating factor (G-CSF) in patients with non-small cell lung cancer (NSCLC) are limited. MONITOR-GCSF is a pan-European, multicentre, prospective, non-interventional study designed to describe patient characteristics, treatment patterns and clinical outcomes in patients receiving biosimilar filgrastim in the prophylaxis of chemotherapy-induced neutropaenia (CIN) and febrile neutropaenia (FN). METHODS: In this subanalysis, patient characteristics, treatment patterns, and outcomes are described for 345 patients with stage 3 or 4 NSCLC, receiving up to six chemotherapy cycles. Patients were treated with biosimilar filgrastim as per their treating physician's best judgement. RESULTS: CIN (any grade) occurred in 13.6% of patients in Cycle 1 and in 36.5% of patients in all cycles. FN occurred in 1.4% of patients in Cycle 1 and in 5.2% of patients in all cycles. Grade 3-4 FN occurred in 1.2% of patients in Cycle 1 and in 3.8% of patients in all cycles. CONCLUSION: Results show that in real-life practice in patients with NSCLC, biosimilar filgrastim has similar effectiveness and safety to the known effectiveness and safety profile of reference filgrastim, supporting the use of biosimilar filgrastim for the real-world treatment of neutropaenia in patients with NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/patologia , Tosse/induzido quimicamente , Substituição de Medicamentos , Feminino , Gastroenterite/induzido quimicamente , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Dor/induzido quimicamente , Resultado do Tratamento
10.
Support Care Cancer ; 27(11): 4283-4292, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30874925

RESUMO

PURPOSE: Few studies are currently available among elderly patients, justifying the need for better understanding of daily medical practices in terms of use of growth factors to prevent chemotherapy (CT)-induced neutropenia. The primary objective of this study was to describe the use of filgrastim in the elderly. METHODS: Cancer patients aged 65 years and above, undergoing CT and initiating a prophylactic treatment with filgrastim, were enrolled. Patients were followed according to routine medical practice from filgrastim initiation until the end of the CT or after a maximum of 6 cycles. RESULTS: One thousand one hundred nineteen evaluable patients were documented in the study (mean age 73.9 ± 6.2 years, 52.1% men). The majority were suffering from solid tumor (73%) with ECOG 0-1 for 80% of them. Approximately two-third had a global risk for FN ≥ 20%, and one third < 20%. Through all CT cycles, no differences were observed between age classes ([65-74], [75-85], or > 85) in dose, duration, and time to first injection from CT start. Most patients (84%) received primary prophylaxis (PP) and 70% were administered during the first CT cycle. The median time from CT start until filgrastim was 4 days. The median duration of filgrastim treatment was 5 days. Dose reductions and CT delays were less frequent in patients receiving PP (4.8% and 7.1% respectively) than secondary prophylaxis (9.2% and 13.3% respectively). CONCLUSIONS: Filgrastim use was consistent with French Market Authorization terms. No difference was shown compared with younger patients. Safety data were consistent with the known safety profile.


Assuntos
Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Idoso , Feminino , Filgrastim/farmacologia , Fármacos Hematológicos/farmacologia , Humanos , Masculino
11.
Basic Clin Pharmacol Toxicol ; 125(2): 117-122, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30916851

RESUMO

Cytochrome P450 3A (CYP3A) is the most relevant drug-metabolizing enzyme in human beings involved in the elimination of about 50% of the marketed drugs. Comprehensive in vivo data of CYP3A activity in palliative patients with haematological diseases are missing. Therefore, CYP3A activity was determined under real-life clinical conditions in patients to gain knowledge about dose adjustments for supportive therapies and symptom management in haematology. The single-arm, prospective trial obtained a 4-hours pharmacokinetic profile of midazolam after oral administration of a microdose as marker substance from each enrolled patient. Plasma concentrations of midazolam and its primary metabolite 1'-hydroxy-midazolam were quantified by mass spectrometry techniques. CYP3A activity was calculated as partial metabolic clearance from an established limited sampling area under the curve. All other drugs taken by the participating patients were considered as well as recent laboratory test results and the patients' diagnoses. Partial metabolic clearance of midazolam in patients with haematological diseases was highly variable (36.9 ± 52.7 L/h). In comparison with the CYP3A activity of healthy individuals, this was a highly significant 30% reduction of activity (P < 0.0001). Dosing of major CYP3A substrate drugs needs to be reduced in palliative patients with haematological diseases, otherwise escalation of debilitating symptoms due to drug interactions might occur.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Fármacos Hematológicos/farmacologia , Doenças Hematológicas/tratamento farmacológico , Midazolam/farmacocinética , Cuidados Paliativos/métodos , Administração Oral , Adulto , Idoso , Área Sob a Curva , Variação Biológica da População , Estudos de Casos e Controles , Interações de Medicamentos , Voluntários Saudáveis , Fármacos Hematológicos/uso terapêutico , Doenças Hematológicas/sangue , Humanos , Taxa de Depuração Metabólica , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Future Oncol ; 15(13): 1525-1533, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30835142

RESUMO

The recombinant G-CSF filgrastim was first approved in 1991, and its value has been evolving ever since. Initial health technology assessments suggested low value due to high drug cost and no evidence for significant gain in overall survival. However, more recent meta-analyses of placebo-controlled randomized trial data show falling costs due to biosimilar competition and absolute overall survival gains of 3.2% (95% CI: 2.1-4.2%) from filgrastim support of cytotoxic chemotherapy. The launch of biosimilar alternatives merits a re-evaluation of decisions by health technology assessments and explains the first inclusion of filgrastim in the WHO Essential Drug List for cancer >20 years after its original approval in 1991, thus demonstrating the power of biosimilar medicines in transforming healthcare.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Humanos , Neoplasias/patologia , Prognóstico
13.
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
14.
J Am Coll Cardiol ; 73(4): 457-476, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30704579

RESUMO

Cardiovascular disease complicating pregnancy is rising in prevalence secondary to advanced maternal age, cardiovascular risk factors, and the successful management of congenital heart disease conditions. The physiological changes of pregnancy may alter drug properties affecting both mother and fetus. Familiarity with both physiological and pharmacological attributes is key for the successful management of pregnant women with cardiac disease. This review summarizes the published data, available guidelines, and recommendations for use of cardiovascular medications during pregnancy. Care of the pregnant woman with cardiovascular disease requires a multidisciplinary team approach with members from cardiology, maternal fetal medicine, anesthesia, and nursing.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Aleitamento Materno , Fármacos Cardiovasculares/farmacocinética , Doenças do Tecido Conjuntivo/complicações , Feminino , Fármacos Hematológicos/uso terapêutico , Hemodinâmica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Gravidez , Complicações Cardiovasculares na Gravidez/etiologia , Teratogênios
15.
Bone Joint J ; 101-B(2): 207-212, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30700116

RESUMO

AIMS: Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol. PATIENTS AND METHODS: A multicentre, prospective, randomized, double-blind, placebo-controlled trial was undertaken involving 229 patients undergoing primary cementless THA using a posterior approach, whose extended rivaroxaban thromboprophylaxis started on the day of surgery. There were 98 male and 131 female patients, with a mean age of 65.5 years (32 to 91). The primary outcome, perioperative RBL, was evaluated at 72 hours postoperatively. The efficacy of short- and long-TXA protocols in the reduction of perioperative RBL was compared with a placebo group. RESULTS: TXA significantly reduced perioperative blood loss compared with placebo (p < 0.001); the mean differences were 525.3 ml (short-TXA vs placebo) and 550.1 ml (long-TXA vs placebo). No venous or arterial thromboembolic complications were reported. The upper boundary of the 95% confidence interval, when comparing short and long protocols, was below the pre-specified margin of non-inferiority (p = 0.027). CONCLUSION: In patients undergoing primary cementless THA, using a posterior approach, who are treated with rivaroxaban for thromboembolic prophylaxis, short- and long-TXA IV protocols are significantly more effective than placebo in reducing perioperative RBL, without any thromboembolic complications. Non-inferiority of a short- versus a long-TXA protocol in reducing perioperative RBL was supported in a secondary analysis.


Assuntos
Artroplastia de Quadril , Perda Sanguínea Cirúrgica/prevenção & controle , Fármacos Hematológicos/uso terapêutico , Artropatias/cirurgia , Rivaroxabana/uso terapêutico , Ácido Tranexâmico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/uso terapêutico , Cimentos para Ossos , Cimentação , Quimioprevenção , Método Duplo-Cego , Inibidores do Fator Xa/uso terapêutico , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
16.
J Stroke Cerebrovasc Dis ; 28(5): 1192-1199, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30711415

RESUMO

BACKGROUND: There are limited clinical studies of bilateral vertebral artery dissection (VAD). OBJECTIVE: To compare the characteristics, imaging findings, and treatments between patients with bilateral and unilateral VAD. METHODS: Between February 2007 and May 2017, 31 (mean age: 53.0 years; 23 men, 8 women) out of 171 VAD patients were hospitalized because of bilateral VAD. Onset type, dissection site, dominant side of the VA, imaging features, treatments, and outcomes were investigated based on medical records. The dominant side of the VA was determined by basi-parallel anatomical scanning. RESULTS: Twenty (64.5%) of 31 patients exhibited bilateral VAD on both sides of V4. The dominant side of the VA was right in 16 patients and left in 15 patients. The pearl and string sign (an angiographical finding with both dilatation and stenosis) was frequently observed on the dominant VAD side, while a tapered occlusion and string sign were most common on the nondominant side. For clinical subtype of VAD, 6 (19.4%) patients had subarachnoid hemorrhage, 10 (32.3%) ischemic stroke, 3 (9.7%) infarction plus subarachnoid hemorrhage, and 12 (38.7%) only headache. The frequency of infarction was increased in bilateral VAD compared with unilateral (P < .05). Surgical intervention was performed in 3 cases, while 14 patients received endovascular intervention. CONCLUSIONS: Infarction occurred frequently in bilateral VAD patients, and 17 patients required an intervention (mainly endovascular) for VA. The treatment strategy varied depending on the clinical subtype, imaging findings of VAD, and morphology of the dominant VAD side.


Assuntos
Angiografia Digital , Angiografia Cerebral/métodos , Procedimentos Endovasculares , Fármacos Hematológicos/uso terapêutico , Procedimentos Neurocirúrgicos , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/terapia , Artéria Vertebral/diagnóstico por imagem , Adulto , Idoso , Anticoagulantes/uso terapêutico , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/etiologia , Infarto Encefálico/terapia , Tomada de Decisão Clínica , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Valor Preditivo dos Testes , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Dissecação da Artéria Vertebral/complicações
17.
Blood ; 133(17): 1865-1875, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-30655275

RESUMO

New treatments directly targeting polymerization of sickle hemoglobin (HbS), the proximate event in the pathophysiology of sickle cell disease (SCD), are needed to address the severe morbidity and early mortality associated with the disease. Voxelotor (GBT440) is a first-in-class oral therapy specifically developed to treat SCD by modulating the affinity of hemoglobin (Hb) for oxygen, thus inhibiting HbS polymerization and downstream adverse effects of hemolytic anemia and vaso-occlusion. GBT440-001 was a phase 1/2 randomized, double-blind, placebo-controlled, single and multiple ascending dose study of voxelotor in adult healthy volunteers and patients with SCD, followed by a single-arm, open-label extension study. This report describes results of voxelotor (500-1000 mg per day) in patients with sickle cell anemia. The study evaluated the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of voxelotor and established proof of concept by improving clinical measures of anemia, hemolysis, and sickling. Thirty-eight patients with SCD received 28 days of voxelotor 500, 700, or 1000 mg per day or placebo; 16 patients received 90 days of voxelotor 700 or 900 mg per day or placebo. Four patients from the 90-day cohort were subsequently enrolled in an extension study and treated with voxelotor 900 mg per day for 6 months. All patients who received multiple doses of voxelotor for ≥28 days experienced hematologic improvements including increased Hb and reduction in hemolysis and percentage of sickled red cells, supporting the potential of voxelotor to serve as a disease-modifying therapy for SCD. Voxelotor was well tolerated with no treatment-related serious adverse events and no evidence of tissue hypoxia. These trials were registered at www.clinicaltrials.gov as #NCT02285088 and #NCT03041909.


Assuntos
Anemia Falciforme/tratamento farmacológico , Benzaldeídos/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Pirazinas/uso terapêutico , Pirazóis/uso terapêutico , Adolescente , Adulto , Benzaldeídos/farmacocinética , Estudos de Casos e Controles , Estudos de Coortes , Método Duplo-Cego , Feminino , Seguimentos , Fármacos Hematológicos/farmacocinética , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prognóstico , Pirazinas/farmacocinética , Pirazóis/farmacocinética , Distribuição Tecidual , Adulto Jovem
18.
Drug Saf ; 42(5): 649-655, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30569267

RESUMO

INTRODUCTION AND OBJECTIVE: Adverse event reports from industry-sponsored programs, such as patient support programs, have contributed to a rise in the number of individual case safety reports in the US Food and Drug Administration Adverse Event Reporting System database. This study aimed to characterize individual case safety reports from industry-sponsored program and non-industry-sponsored program sources and compare their usefulness in safety signal detection. METHODS: Individual case safety reports of six drug and biological products were identified in the Food and Drug Administration Adverse Event Reporting System database between the date of Food and Drug Administration product approval and the first quarter of 2017. A random subset of industry-sponsored program and non-industry-sponsored program individual case safety reports were then compared to identify differences in reporters, outcomes, data completeness, and usefulness. The 'usefulness' of individual case safety reports was assessed by manually reviewing the availability of key information in the narrative (e.g., temporality, comorbidities). RESULTS: Compared with non-industry-sponsored program reports, more industry-sponsored program reports were associated with a serious outcome (51.4% vs. 58.8%, p = 0.02) and were reported by consumers (35.5% vs. 50.4%, p < 0.01). Industry-sponsored program reports tended to contain more data elements than non-industry-sponsored program reports (i.e., age, sex, indication for use), but completeness was variable across products. No significant difference in usefulness was identified between non-industry-sponsored program and industry-sponsored program individual case safety reports (30.6% vs. 28.5%, p = 0.42). Useful reports that contained at least one serious, unlabeled adverse event represented only 4% and 6.2% of the non-industry-sponsored program and industry-sponsored program report cohorts, respectively. CONCLUSIONS: Our study suggests that reports obtained from industry-sponsored programs in the Food and Drug Administration Adverse Event Reporting System database contain more data elements but are similar to non-industry-sponsored program reports with regard to 'usefulness' in signal detection.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Indústria Farmacêutica , Vigilância de Produtos Comercializados/normas , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Fármacos Hematológicos/efeitos adversos , Fármacos Hematológicos/uso terapêutico , Humanos
20.
Cancer ; 125(7): 1143-1154, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548485

RESUMO

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.


Assuntos
Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Leucemia Mieloide Aguda/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Síndromes Mielodisplásicas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neutropenia/prevenção & controle , Polietilenoglicóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Armazenamento e Recuperação da Informação , Masculino , Medicare , Neutropenia/induzido quimicamente , Rituximab/efeitos adversos , Programa de SEER , Estados Unidos/epidemiologia
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