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1.
Ann Hematol ; 99(5): 1063-1072, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32248251

RESUMO

These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rates (ORRs), and safety. Eighty-three eligible patients were enrolled between October 2012 and August 2014. The median PFS was 28.0 months (95% CI 19.6-36.7) and the median OS was 55.3 months (95% CI 51.6-NA). Among the patients who received lenalidomide maintenance therapy, median PFS was significantly improved in patients who had achieved a very good partial response (VGPR) or better (41.8 vs 20.7 months, p = 0.0070). As the best response, the rates of partial response or better were 85.5% comprising stringent complete response (sCR, 21.7%), complete response (CR, 10.8%), VGPR (18.1%), and partial response (PR, 34.9%). The most frequently observed grade 3 or higher adverse events during the VMP therapy were anemia (28.9%), neutropenia (15.6%), thrombocytopenia (6.0%), and peripheral neuropathy (2.4%). The most frequently observed grade 3 or higher adverse events during the Rd therapy were anemia (3.5%), neutropenia (1.8%), and skin rush (5.3%). The most frequently observed grade 3 or higher adverse events during lenalidomide maintenance therapy were anemia (7.4%) and neutropenia (24.1%). Thus, VMP induction therapy followed by Rd consolidation and lenalidomide maintenance is considered a well-tolerated and effective regimen in transplant-ineligible NDMM. This trial is registered with UMIN-CTR with the identification number UMIN000009042.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Taxa de Sobrevida
2.
Internist (Berl) ; 61(3): 313-320, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-31965234

RESUMO

A 78-year-old woman with rheumatoid arthritis on TNF-α inhibitor, methotrexate and prednisolone presented with severe but unspecific symptoms such as leg weakness, shivering, bifrontal headache, nausea and staggering. The broad range of differential diagnoses lead to intricate and time-consuming diagnostic procedures. Serology, magnetic resonance imaging and microbiological investigations represent important steps to make the final diagnosis of cerebral toxoplasmosis. Both diagnostic approach and therapy require close cooperation of different disciplines. Therapies of rheumatoid arthritis as well as of toxoplasmosis are based on a long-term treatment and could be associated with numerous harmful side effects. Continuous monitoring and permanent adjustment of therapy regimes are therefore mandatory.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Infecções Oportunistas/diagnóstico , Prednisolona/uso terapêutico , Toxoplasmose Cerebral/diagnóstico , Fator de Necrose Tumoral alfa/uso terapêutico , Idoso , Antirreumáticos/efeitos adversos , Encéfalo/fisiopatologia , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Imagem por Ressonância Magnética/métodos , Metotrexato/efeitos adversos , Prednisolona/efeitos adversos , Toxoplasmose Cerebral/diagnóstico por imagem , Toxoplasmose Cerebral/imunologia , Toxoplasmose Cerebral/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/efeitos adversos
3.
Ann Hematol ; 99(1): 137-145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768675

RESUMO

The combinations of melphalan, bortezomib, and prednisolone (VMP) and of lenalidomide and dexamethasone (Rd) are standard treatment strategies for transplant-ineligible newly diagnosed multiple myeloma (NDMM). To make the most of these two strategies, we investigated the efficacy and feasibility of first-line treatment with 4 cycles of VMP followed by continuous Rd therapy in a multi-institutional phase 2 study in Japanese patients with transplant-ineligible NDMM. Thirty-six patients of median age 74 years old with NDMM initially received 35-day cycles of VMP: oral melphalan (6 mg/m2) and prednisolone (60 mg/m2) on days 1 to 4 and bortezomib (1.3 mg/m2) on days 1, 8, 15, and 22. After 4 cycles of VMP, treatment was switched to 28-day cycles of Rd, which was continued until disease progression or emergence of an unacceptable adverse event (AE) in 33 patients, while one patient who achieved CR after VMP continued VMP at the physician's discretion. The overall response rates after VMP and after Rd were 66.7% and 86.1%, including CR rates of 5.6% and 36.1%, respectively. In a median follow-up period of 34.3 months, the progression-free survival and overall survival rates at 3 years were 43.2% and 81.3%, respectively. Grade 3-4 hematological AEs included neutropenia (39% with VMP and 24% with Rd) and thrombocytopenia (11% with VMP and 3% with Rd). There was no death due to an AE. In conclusion, sequential therapy with VMP followed by Rd is effective and mostly feasible for transplant-ineligible NDMM. The study is registered as UMIN000034815.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Mieloma Múltiplo/diagnóstico , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Taxa de Sobrevida
4.
Lancet ; 394(10213): 1993-2001, 2019 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-31727410

RESUMO

BACKGROUND: Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation. METHODS: The HOPE study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands. Patients were considered eligible if they had symptomatic hand osteoarthritis and signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients were required to have four or more DIP/PIP joints with osteoarthritic nodes; at least one DIP/PIP joint with soft swelling or erythema; at least one DIP/PIP joint with a positive power Doppler signal or synovial thickening of at least grade 2 on ultrasound; and finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug (NSAID) washout (defined as worsening of finger pain by at least 20 mm on the VAS). Eligible patients were randomly assigned (1:1) to receive 10 mg prednisolone or placebo orally once daily for 6 weeks, followed by a 2-week tapering scheme, and a 6-week follow-up without study medication. The patients and study team were masked to treatment assignment. The primary endpoint was finger pain, assessed on a VAS, at 6 weeks in participants who had been randomly assigned to groups and attended the baseline visit. This study is registered with the Netherlands Trial Registry, number NTR5263. FINDINGS: We screened patients for enrolment between Dec 3, 2015, and May 31, 2018. Patients completed baseline visits and started treatment between Dec 14, 2015, and July 2, 2018, and the last study visit of the last patient was Oct 4, 2018. Of 149 patients assessed for eligibility, 57 (38%) patients were excluded (predominantly because they did not meet one or several inclusion criteria, most often because of an absence of synovial inflammation or of flare-ups after NSAID washout) and 92 (62%) patients were eligible for inclusion. We randomly assigned 46 (50%) patients to receive prednisolone and 46 (50%) patients to receive placebo, all of whom were included in the modified intention-to-treat analysis of the primary endpoint. 42 (91%) patients in the prednisolone group and 42 (91%) in the placebo group completed the 14-week study. The mean change between baseline and week 6 on VAS-reported finger pain was -21·5 (SD 21·7) in the prednisolone group and -5·2 (24·3) in the placebo group, with a mean between-group difference (of prednisolone vs placebo) of -16·5 (95% CI -26·1 to -6·9; p=0·0007). The number of non-serious adverse events was similar between the groups. Five serious adverse events were reported during our study: one serious adverse event in the prednisolone group (a myocardial infarction) and four serious adverse events in the placebo group (an infected traumatic leg haematoma that required surgery, bowel surgery, atrial fibrillation that required a pacemaker implantation, and symptomatic uterine myomas that required a hysterectomy). Four (4%) patients discontinued the study because of an adverse event: one (2%) patient receiving prednisolone (for a myocardial infarction) and three (7%) patients receiving placebo (for surgery of the bowel and for an infected leg haematoma and for Lyme disease arthritis of the knee). INTERPRETATION: Treatment with 10 mg prednisolone for 6 weeks is efficacious and safe for the treatment of patients with painful hand osteoarthritis and signs of inflammation. The results of our study provide clinicians with a new short-term treatment option for patients with hand osteoarthritis who report a flare-up of their disease. FUNDING: Dutch Arthritis Society.


Assuntos
Anti-Inflamatórios/administração & dosagem , Mãos , Osteoartrite/tratamento farmacológico , Prednisolona/administração & dosagem , Idoso , Anti-Inflamatórios/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Resultado do Tratamento
5.
Ann Hematol ; 98(12): 2805-2814, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31620815

RESUMO

In the ALCYONE trial, daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) reduced the risk of disease progression or death by 50% versus bortezomib, melphalan, and prednisone (VMP) in patients with transplant-ineligible newly diagnosed multiple myeloma. Here, we report a subanalysis of East Asian patients from ALCYONE. After a median follow-up of 17.1 and 15.9 months for Japanese (n = 50) and Korean (n = 41) patients, respectively, median progression-free survival for D-VMP versus VMP was not reached (NR) versus 20.7 months in Japanese patients and NR versus 14.0 months in Korean patients. The overall response rate for D-VMP versus VMP was 96% versus 92% in Japanese patients and 91% versus 61% in Korean patients. Using next-generation sequencing, minimal residual disease negativity at 10-5 sensitivity for D-VMP versus VMP was 33% versus 8% among Japanese patients and 17% versus 0% among Korean patients. Rates of any grade and grade 3/4 pneumonia were consistent with the rates observed for the global safety population. Similar efficacy and safety findings were observed in the combined Japanese and Korean subgroup and ≥ 75 years of age subgroup. In conclusion, D-VMP was safe and efficacious in East Asian patients, consistent with the global ALCYONE population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Intervalo Livre de Doença , Extremo Oriente/epidemiologia , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Taxa de Sobrevida
6.
Cardiovasc Pathol ; 43: 107146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31499334

RESUMO

Myocardial calcification, a rare disease that leads to chronic or acute heart failure and with a poor prognosis, occurs in patients with abnormal calcium-phosphorus metabolism. The association between myocardial calcification and tumor lysis syndrome has not been reported to date. A 50-year-old man with hyperthermia and general malaise presented to our hospital and was clinically diagnosed with B-lymphoblastic leukemia (B-ALL) and febrile neutropenia accompanied by septic shock. Prednisolone was administered for tumor reduction. Two to three hours later, electrocardiography demonstrated ST elevation in V4-6, and blood tests showed elevated levels of cardiac enzymes. Transthoracic echocardiogram revealed diffuse severe hypokinesis with decreased left ventricular ejection fraction. Additionally, blood tests showed that serum phosphorus level increased to 8.0 mg/dl, which was likely due to tumor lysis syndrome. Circulatory and respiratory failure due to left heart failure progressed, and he died 3 days after administration of prednisolone. Pathological autopsy revealed diffuse proliferation of atypical B-lymphoblasts in the bone marrow, which led to the pathological diagnosis of B-ALL, accompanied by necrosis. On the cut surface of the heart, the left ventricle was dilated, and patchy yellowish-brown areas were present in the epicardial-side of the myocardium and spread through the circumferential wall of the left ventricle and interventricular septum. Microscopically, myocardial fibers were granularly basophilic in that area and were revealed as calcium deposits by Von Kossa staining. He was diagnosed with myocardial calcification. The drastic increase in the serum phosphorus level caused by tumor lysis syndrome seemed to be associated with myocardial calcification.


Assuntos
Antineoplásicos/efeitos adversos , Calcinose/etiologia , Cardiomiopatias/etiologia , Miocárdio/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Prednisolona/efeitos adversos , Síndrome de Lise Tumoral/etiologia , Autopsia , Biomarcadores/sangue , Calcinose/sangue , Calcinose/patologia , Cardiomiopatias/sangue , Cardiomiopatias/patologia , Causas de Morte , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Fósforo/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Síndrome de Lise Tumoral/sangue , Síndrome de Lise Tumoral/patologia , Regulação para Cima
7.
Food Funct ; 10(9): 6184-6192, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501830

RESUMO

Glucocorticoids (GCs) are widely used to treat a variety of autoimmune diseases, but long-term use can lead to osteoporosis. To elucidate the mechanism of osteoporosis caused by glucocorticoids and to find effective protective drugs/foods, osteoblasts treated by prednisolone acetate were studied and salvianolic acid B (Sal B) was added to osteoblasts. The results showed that Sal B increased the activity of ALP and stimulated the expression of ALP that had been suppressed by prednisolone acetate. To further study the mechanisms of the protective effect of Sal B on osteoblasts treated with prednisolone acetate, the effects of gene expression involved with bone formation and differentiation were studied. The results show that the mRNA and protein expression of Runx2, Osx, OCN, IGF-I, Col-I and HO-I was up-regulated by Sal B. In conclusion, by stimulating the osteoblast activity and the expression of genes related to bone formation and differentiation, Sal B had a protective effect on osteoblasts that had been treated with prednisolone acetate.


Assuntos
Benzofuranos/farmacologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Osteoblastos/metabolismo , Prednisolona/efeitos adversos , Prednisolona/análogos & derivados , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Internist (Berl) ; 60(11): 1201-1208, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31511906

RESUMO

This article reports about a 73-year-old woman of Bosnian descent who presented with acute renal failure. A renal biopsy was diagnostic for a postinfect necrotizing and extracapillary proliferative glomerulonephritis. The patient reported a febrile infection fever 2 weeks previously. The diagnostics did not reveal any indications of an ongoing infection. The glomerulonephritis responded to treatment with systemic steroids. The patient was readmitted to hospital 6 weeeks later in a severely ill condition. A gastric biopsy revealed a Strongyloides stercoralis infestation. Due to the systemic steroid therapy the patient had developed a so-called hyperinfection syndrome and died despite treatment on the intensive care unit. This case illustrates the need for awareness of this rare parasitosis, particularly in patients from endemic areas. A likely causal relationship with the glomerulonephritis is discussed and an overview of the diagnostics, course of the disease and treatment of this parasitosis is given.


Assuntos
Lesão Renal Aguda/etiologia , Glomerulonefrite/tratamento farmacológico , Prednisolona/efeitos adversos , Esteroides/efeitos adversos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Idoso , Animais , Antiparasitários/uso terapêutico , Evolução Fatal , Feminino , Glomerulonefrite/diagnóstico , Humanos , Ivermectina/uso terapêutico , Prednisolona/uso terapêutico , Esteroides/uso terapêutico , Estômago/microbiologia , Estômago/patologia , Estrongiloidíase/complicações , Estrongiloidíase/tratamento farmacológico
9.
Pediatrics ; 144(3)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31416827

RESUMO

OBJECTIVES: The use of either prednisolone or low-dose dexamethasone in the treatment of childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg. METHODS: Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age >6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment. RESULTS: Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval -0.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval -0.07 to 0.17) for prednisolone. Re-attendance rates were 17.8% for dexamethasone, 19.5% for low-dose dexamethasone, and 21.7% for prednisolone (not significant [P = .59 and .19]). CONCLUSIONS: Noninferiority was demonstrated for both low-dose dexamethasone and prednisolone. The type of oral steroid seems to have no clinically significant impact on efficacy, both acutely and during the week after treatment.


Assuntos
Crupe/tratamento farmacológico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Administração Oral , Pré-Escolar , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Serviço Hospitalar de Emergência , Estudos de Equivalência como Asunto , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Austrália Ocidental
10.
Int J Hematol ; 110(4): 458-465, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321731

RESUMO

The standard treatment for adult acute lymphoblastic leukemia (ALL) is undefined. Patients with newly diagnosed standard-risk ALL at a single institution were retrospectively analyzed. From 2010 to 2017, 46 patients were treated using the modified Berlin-Frankfurt-Münster (BFM)-ALL-95 regimen. Hematologic and molecular complete remission (CR) rates of 91.3% and 76.1% were achieved. The 5-year event-free survival (EFS) and overall survival (OS) rates for all patients in the cohort were 58.0% (95% confidence interval, 42.1-73.9%) and 66.7% (95% CI, 51.4-82.0%), respectively. No patient presented with central nervous system involvement after CR in this study. This condition could be related to four doses of high-dose methotrexate (MTX) every 3 months during the maintenance phase. Multivariate analysis revealed that minimal residual disease positive and time interval between induction IA and Protocol M of more than 70 days were independent adverse factors for EFS and OS. One or more instances of grade 4 myelosuppression occurred during induction therapy. Nonhematological side effects were mild. No toxicity-related deaths were observed in the entire cohort. The data indicated that the modified regimen is well tolerated and can produce the promising outcomes in Chinese adults with standard-risk ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Mercaptopurina/administração & dosagem , Mercaptopurina/efeitos adversos , Metotrexato/administração & dosagem , Neoplasia Residual , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Risco , Fatores de Tempo , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
11.
Early Hum Dev ; 136: 1-6, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31265946

RESUMO

BACKGROUND: There are few published data on the efficacy and safety of prednisolone in preterm infants with bronchopulmonary dysplasia (BPD). AIMS: To describe the use of chronic prednisolone therapy in a population of infants with severe BPD, examine potential benefits on respiratory status, and document potential effects on growth. STUDY DESIGN: Single-center retrospective cohort study. SUBJECTS: Preterm infants who had received ≥30 days of prednisolone for the treatment of severe BPD. OUTCOME MEASURES: Weekly changes in Pulmonary Severity Score (PSS), as well as weekly changes in weight, length, and head circumference during prednisolone therapy. RESULTS: Forty-three infants (mean birth weight 729 g; mean gestational age 26 weeks) were identified. The average age at start of prednisolone treatment was 42.5 ±â€¯5.9 weeks; while the median duration and median cumulative dose of prednisolone therapy were 67 (IQR 57-107) days and 61.3 (IQR 39.9-93.3) mg/kg, respectively. PSS decreased after 1 week of prednisolone therapy (mean difference, 0.19; 95% Cl, 0.01 to 0.37; p = 0.03). No further reduction in PSS was noted despite continued treatment. Length z-scores decreased after 4 weeks of continued treatment (mean difference 0.6; 95% CI 0.01 to 1.1; P = 0.04), while weight and head circumference did not change. CONCLUSIONS: In one of the first reports on prednisolone therapy for severe BPD, we describe that long-term prednisolone is associated with modest short-term improvement in PSS, but impairs linear growth. Our results suggest a risk-benefit profile of prednisolone that does not favor long-term use in infants with severe BPD.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Glucocorticoides/uso terapêutico , Lactente Extremamente Prematuro , Prednisolona/uso terapêutico , Desenvolvimento Infantil/efeitos dos fármacos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Recém-Nascido , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos
12.
Am J Vet Res ; 80(8): 743-755, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31339769

RESUMO

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.


Assuntos
Anti-Inflamatórios/farmacologia , Gatos , Glucocorticoides/farmacologia , Prednisolona/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Doenças do Gato/tratamento farmacológico , Dermatite/tratamento farmacológico , Dermatite/veterinária , Ecocardiografia/efeitos dos fármacos , Ecocardiografia/veterinária , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Distribuição Aleatória
13.
BMJ ; 365: l1800, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31335316

RESUMO

OBJECTIVE: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. DESIGN: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. SETTING: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. PARTICIPANTS: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. INTERVENTIONS: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). MAIN OUTCOME MEASURES: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. RESULTS: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval -0.005 to 0.037) and cost savings (difference -£1673 ($2160; €1930), 95% confidence interval -£3455 to £109). CONCLUSIONS: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. TRIAL REGISTRATION: ISRCTN16645249; EudraCT 2010-022489-29.


Assuntos
Assistência de Longa Duração , Síndrome Nefrótica , Prednisolona , Qualidade de Vida , Prevenção Secundária , Adolescente , Criança , Pré-Escolar , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/economia , Humanos , Imunossupressores/uso terapêutico , Lactente , Análise de Intenção de Tratamento , Assistência de Longa Duração/economia , Assistência de Longa Duração/métodos , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/economia , Síndrome Nefrótica/psicologia , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/economia , Prevenção Secundária/economia , Prevenção Secundária/métodos , Resultado do Tratamento
14.
Int J Hematol ; 110(4): 447-457, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325152

RESUMO

We conducted a phase I study to determine the recommended dose of thalidomide combined with melphalan plus prednisolone (MPT) and a phase II study evaluating the efficacy and safety of this MPT regimen in transplant-ineligible Japanese patients with untreated multiple myeloma. The recommended dose was determined to be 100 mg/day in the phase I study. In the phase II, randomized, double-blind, parallel-group study, patients were allocated to either MPT (n = 52) or MP (n = 51), with 21 and 29 patients completing the study, respectively. Overall response rate, the primary endpoint, was significantly higher in the MPT [40.4% (21/52 patients), 95% confidence interval (CI) 27.0-54.9%] than in the MP [19.6% (10/51 patients), 95% CI 9.8-33.1%] group (P = 0.022). Time to response was also significantly shorter in the MPT group. Incidences of hematological toxicities were similar in the two groups, suggesting that addition of thalidomide did not increase hematological toxicity. Although incidences of some non-hematological toxicities tended to be higher in the MPT group, the low incidence of ≥ Grade 3 toxicities suggests that MPT therapy was well tolerated. These results support the safety and efficacy of MPT therapy in untreated Japanese multiple myeloma patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Autoenxertos , Método Duplo-Cego , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Transplante de Células-Tronco , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
15.
BMJ Case Rep ; 12(5)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31088812

RESUMO

A 77-year-old man, who was taking prednisolone 7.5 mg, underwent wedge resection for nodules in the right lower lobe of the lung. The nodules were diagnosed as amyloid tumour. On the sixth postoperative day, sudden tachycardia, fever, creatine phosphokinase increase, renal dysfunction and metabolic acidosis were observed. CT showed no signs of infection, exacerbation of interstitial pneumonia, pulmonary embolism or occlusion in the major vessels of the mesentery. Exploratory laparotomy revealed intestinal necrosis in the inferior mesenteric artery area, and left hemicolectomy was performed. Postoperative pathological examination revealed gangrenous ischaemic colitis. Although gangrenous ischaemic colitis is not a complication specific to general thoracic surgery, it can be fatal. Because of the high risk of developing gangrenous ischaemic colitis in elderly patients and the increase in concomitant diseases, thoracic surgeons should always be mindful of the condition.


Assuntos
Colite Isquêmica/cirurgia , Gangrena/patologia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Prednisolona/administração & dosagem , Idoso , Colite Isquêmica/diagnóstico por imagem , Colite Isquêmica/etiologia , Colite Isquêmica/patologia , Gangrena/etiologia , Gangrena/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Prednisolona/efeitos adversos , Tomografia Computadorizada por Raios X
16.
G Chir ; 40(2): 112-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131809

RESUMO

AIM: Uterine rupture during pregnancy is a rare but life threatening event in Obstetrics, with potentially catastrophic consequences for both the fetus and the mother. There are few published case reports that investigate the possible association between long-term steroid treatment and uterine rupture during the antenatal period. CASE REPORT: A 33-year-old G2P1 woman with obstetrical history of one previous transverse low-segment caesarean section presented at the 30th week of gestation with severe abdominal pain which started spontaneously one hour before. She had medical history of pemphigus under long-term treatment with prednisolone. Clinical examination showed acute abdomen while the fetus developed heart rate decelerations. Emergency caesarean section via Pfannenstiel incision under general anaesthesia was performed. Uterine rupture was recognised with localization not at the scar of the previous caesarean section but at the left posterolateral site of the uterine fundus. A healthy premature male infant with an excellent Apgar score and weight of 1510 gr. was delivered by a low-segment caesarean section. Surgical repair of the site of the rupture with isolated sutures followed. There was no need for hysterectomy as hemorrhage was controlled and hemodynamic stability of the woman was restored. DISCUSSION: Uterine rupture should be included in the differential diagnosis by all obstetricians not only during labour but in acute abdominal pain during the antenatal period as well.


Assuntos
Glucocorticoides/efeitos adversos , Prednisolona/efeitos adversos , Complicações na Gravidez/induzido quimicamente , Ruptura Uterina/induzido quimicamente , Adulto , Feminino , Humanos , Gravidez , Medição de Risco , Fatores de Risco
17.
Int J Cancer ; 145(9): 2459-2467, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973963

RESUMO

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 µg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.


Assuntos
Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Hematínicos/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/metabolismo , Hemoglobinas/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Estudos Prospectivos , Rituximab/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico
18.
Medicine (Baltimore) ; 98(13): e14636, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921179

RESUMO

BACKGROUND: The systemic use of corticosteroids for patients in severe community-acquired pneumonia (CAP) remains disputed in clinical practice. We undertook a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with severe CAP. METHODS: We searched MEDLINE (1946 to June 2018), EMBASE (1966 to June 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for severe CAP. The endpoints of the study included total mortality, length of intensive care unit (ICU) stay and mechanical ventilation. RESULTS: Nine trials which contained 914 patients were included for final meta-analysis. Of the 488 patients in the corticosteroid group, there were 37 deaths (7.58%) and 56 deaths occurred in 426 patients in the control group (13.1%). Corticosteroid therapy was associated with a lower rate of all-cause mortality compared to control (odd ratio [OR] 0.63, 95% confidence interval [CI] 0.42-0.95, P = .03). Subgroup analysis was conducted to show that the drug type modified the effect of steroids for mortality rate: prednisolone or methylprednisolone therapy (OR 0.37, 95% CI 0.19-0.72) reduced total mortality, whereas hydrocortisone use did not (OR 0.90, 95% CI 0.54-1.49). We found the length of ICU stay was significantly shorter in the steroid group compared to control (MD -2.52 days, 95% CI -4.88 to -0.15; P = .04). And there was a reduction trend in the need for mechanical ventilation in corticosteroid group (OR 0.53, 95% CI 0.28-1.02; P = .06). There was no trend towards more adverse events in the corticosteroid arm compared to control (OR 0.92, 95% CI 0.58-1.47; P = .74). CONCLUSION: Overall, adjunctive systemic corticosteroids therapy was effective and safe for patients with severe CAP. In addition, the effects of mortality may differ according to the type of corticosteroids.


Assuntos
Corticosteroides/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Hidrocortisona/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia/tratamento farmacológico , Prednisolona/uso terapêutico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Idoso , Infecções Comunitárias Adquiridas/epidemiologia , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Mortalidade/tendências , Pneumonia/mortalidade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Clin Biochem ; 67: 33-39, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30914158

RESUMO

OBJECTIVE: Corticosteroids may cause hyperglycemia and diabetes mellitus (DM). Development of DM during long-term steroid use has been well studied; however, data regarding the short-term effects of steroid therapy are scarce. In this study, we aimed to detect the actual time of short-term steroid-induced hyperglycemia in patients without previous impaired glucose metabolism, and the ideal time (which day and in relation to meals) of glucose measurement. METHODS: The 7-point blood glucose (BG) measurements of patients who were commenced moderate to high-dose steroids (≥15 mg/day prednisolone or its equivalent) due to rheumatological diseases during the first 5 days of steroid therapy were recorded. Fasting BG ≥ 7 mmol/L (126 mg/dL) or random BG ≥ 11.1 mmol/L (200 mg/dL) were considered as overt DM in accordance with the 2016 American Diabetes Association guideline, and post-meal BG ≥10 mmol/L (180 mg/dL) was considered as steroid-induced hyperglycemia. RESULTS: Fifteen males (mean age: 44 ±â€¯16 years) and 35 females (mean age: 41 ±â€¯12 years) were recruited to the study. One thousand seven hundred fifty fasting, pre-meal, and 2-hours post-meal BG concentrations were analyzed. Twenty-one (42%) patients developed steroid-induced DM and 39 (78%) developed steroid-induced hyperglycemia. The highest glucose concentrations were detected on the 3rd day of steroid therapy and 2-h after meals (p < .0001). CONCLUSION: Intermediate to high-dose steroid therapy causes hyperglycemia after lunch and dinner on the 3rd day of treatment. This time period should be taken into consideration in the detection and treatment of steroid-induced hyperglycemia.


Assuntos
Corticosteroides , Glicemia/metabolismo , Hiperglicemia , Prednisolona , Doenças Reumáticas , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Doenças Reumáticas/sangue , Doenças Reumáticas/tratamento farmacológico
20.
Expert Opin Investig Drugs ; 28(5): 489-496, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30908082

RESUMO

BACKGROUND: An efficacious anti-inflammatory corticosteroid with reduced side effects has been long sought. We report the pooled results from three clinical proof-of-mechanism Phase I studies of BI 653048 in healthy subjects, a functionally selective, nonsteroidal glucocorticoid (GC). RESEARCH DESIGN AND METHODS: Three Phase I trials were conducted: a single rising-dose study and a multiple rising-dose study to evaluate the safety, tolerability, and pharmacokinetics of BI 653048, and a multiple parallel-arm-dose study with intravenous lipopolysaccharide challenge to assess in vivo pharmacodynamics. The pharmacodynamics, efficacy, and safety of BI 653048 and prednisolone were compared. RESULTS: Treatment with 200 mg BI 653048 was associated with a reduced expression of IL1R2, ITGB3, and SDPR versus 20 mg prednisolone; comparable levels of FKBP5, ZBTB16, and DDIT4 expression were observed. Changes in C-peptide, glucose, insulin, and cortisol were moderate compared with prednisolone. A greater reduction of osteocalcin was observed with 200 mg BI 653048 versus 20 mg prednisolone. Comparable anti-inflammatory efficacy was demonstrated for 200 mg BI 653048 and 20 mg prednisolone. BI 653048 was well tolerated in healthy subjects. CONCLUSION: BI 653048 demonstrated the desired anti-inflammatory effects of the nonsteroidal GC; however, the undesirable side-effect profile associated with GC steroids could not be disassociated from BI 653048. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02217644, NCT02217631, and NCT02224105.


Assuntos
Anti-Inflamatórios/farmacologia , Benzamidas/farmacologia , Glucocorticoides/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Receptores de Glucocorticoides/agonistas , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Ensaios Clínicos Fase I como Assunto , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Osteocalcina/metabolismo , Prednisolona/efeitos adversos , Prednisolona/farmacologia , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
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