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1.
Medicine (Baltimore) ; 99(33): e21121, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871981

RESUMO

BACKGROUD: Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and efficacy of MMF in patients with LN, no definitive meta-analysis has yet been conducted in Chinese patients. This analysis investigated the efficacy and safety of MMF in Chinese patients with proliferative LN. METHODS: A systematic literature search was conducted to select randomized controlled trials that reported at least one of the following: complete remission (CR), partial remission, total remission (TR; defined as complete remission + partial remission), relapse rate, serum creatinine, creatinine clearance, end-stage renal disease, death, infections, amenorrhea, leukopenia, alopecia, gastrointestinal symptoms, or liver damage. RESULTS: Eighteen trials (927 patients) were included; 14 (750 patients) reported CR, partial remission, and TR. Two trials (58 patients) reported relapse rates during maintenance treatment. MMF induction significantly improved CR and TR vs cyclophosphamide (relative risk 1.34, 95% confidence interval: 1.13-1.58; P < .001; relative risk 1.16, 95% confidence interval: 1.02-1.33; P = .03), and was associated with significantly lower risks of infection (P < .001), amenorrhea (P < .001), leukopenia, and alopecia. No significant difference in relapse rate was evident between the MMF and azathioprine groups (P = .66). CONCLUSION: According to this meta-analysis of 18 trials, MMF is significantly more effective than cyclophosphamide induction, and is associated with reduced incidences of infections, amenorrhea, leukopenia, and alopecia in Chinese patients with proliferative LN.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etnologia , Ácido Micofenólico/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Inibidores Enzimáticos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Clin Drug Investig ; 40(9): 847-859, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621143

RESUMO

BACKGROUND AND OBJECTIVES: Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used for the management of hyperuricemic patients with or without gout in Japan. Accumulating evidence has demonstrated the efficacy of topiroxostat for the treatment of hyperuricemia with or without gout. However, the safety and efficacy of topiroxostat in the clinical setting remain unclear, and there is little large-scale clinical evidence. We conducted a post-marketing observational study over 54 weeks. PATIENTS AND METHODS: Patients were centrally enrolled, and case report forms of 4491 patients were collected between April 2014 and March 2019 from 825 medical sites. RESULTS: Overall, 4329 patients were assessed for safety and 4253 patients for effectiveness. The overall incidence of adverse drug reactions was 6.95%, and the incidence rates of adverse drug reactions of gouty arthritis, hepatic dysfunction, and skin disorders, which are of special interest in this study, were 0.79%, 1.73%, and 0.95%, respectively. No case of serious gouty arthritis was observed. Serum urate levels decreased stably over time and showed a significant reduction rate at 54 weeks (21.19% ± 22.07%) and on the final visit (19.91% ± 23.35%) compared to the baseline. The rates for subjects who achieved serum uric acid levels ≤ 6.0 mg/dL at 18 and 54 weeks after administration were 43.80% and 48.28%, respectively. CONCLUSIONS: This study suggests that there is no particular concern about adverse drug reactions or the efficacy of topiroxostat for hyperuricemic patients with or without gout in a post-marketing setting in Japan.


Assuntos
Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Nitrilos/uso terapêutico , Vigilância de Produtos Comercializados , Piridinas/uso terapêutico , Xantina Desidrogenase/antagonistas & inibidores , Adulto , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Supressores da Gota/efeitos adversos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Piridinas/efeitos adversos , Resultado do Tratamento , Ácido Úrico/sangue
3.
BMC Infect Dis ; 20(1): 478, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631240

RESUMO

BACKGROUND: Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir. CASE PRESENTATION: A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/µL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2. CONCLUSIONS: In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.


Assuntos
Antivirais/uso terapêutico , Ciclopentanos/uso terapêutico , Farmacorresistência Viral/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Guanidinas/uso terapêutico , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/tratamento farmacológico , Oxazinas/uso terapêutico , Piridinas/uso terapêutico , Tiepinas/uso terapêutico , Triazinas/uso terapêutico , Ciclopentanos/efeitos adversos , Ciclopentanos/farmacologia , Farmacorresistência Viral/genética , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Guanidinas/efeitos adversos , Guanidinas/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hospedeiro Imunocomprometido , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Neuraminidase/antagonistas & inibidores , Neuraminidase/genética , Oseltamivir/uso terapêutico , Transplante Homólogo/métodos , Resultado do Tratamento , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética
4.
N Engl J Med ; 382(26): 2504-2513, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579811

RESUMO

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina , Falha de Tratamento
5.
Circ Heart Fail ; 13(7): e007220, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32500721

RESUMO

The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.


Assuntos
Síndrome Coronariana Aguda/terapia , Arritmias Cardíacas/terapia , Infecções por Coronavirus/terapia , Insuficiência Cardíaca/terapia , Miocardite/terapia , Pneumonia Viral/terapia , Síndrome Coronariana Aguda/complicações , Antibacterianos/efeitos adversos , Antivirais/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/complicações , Azitromicina/efeitos adversos , Betacoronavirus , Cardiotônicos/uso terapêutico , Doença Crônica , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/terapia , Inibidores Enzimáticos/efeitos adversos , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/etiologia , Coração Auxiliar , Humanos , Hidroxicloroquina/efeitos adversos , Balão Intra-Aórtico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Miocardite/complicações , Pandemias , Intervenção Coronária Percutânea , Pneumonia Viral/complicações , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Tromboembolia
6.
Medicine (Baltimore) ; 99(26): e20719, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590747

RESUMO

BACKGROUND: Regorafenib, a multitargeted tyrosine kinase inhibitor, proved to be active in patients with soft tissue sarcomas (STS). METHODS: We conducted an open-label, non-randomized, single-center phase II study in advanced pretreated STS patients. Patients received regorafenib 160 mg daily on days 1 enrule 21 of a 28-day cycle. The primary endpoint was the progression-free survival (PFS) at 8 weeks. Toxicity was registered. RESULTS: Between April 2015 and November 2016, 21 patients were enrolled in the trial. A total of 13 out of 21 evaluable patients (61.9%) were progression-free at 8 weeks. Median PFS was 3.8 months (95% CI: 2.1-9.4). Median overall survival was 14.8 months (95% CI: 7.7-27.8). In the intention-to-treat population, we reported a PFS of 66.7% at 3 months (95% CI: 40.4-83.4) and 16.7% at 12 months (95% CI: 4.1-36.5). As per the RECIST criteria, the response rate was 4.7% (1 partial response out of 21 evaluable patients) with a clinical benefit rate of 61.9%; no complete response was observed. Treatment was well tolerated. CONCLUSION: Regorafenib shows signs of clinical activity in patients with advanced STS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02307500.


Assuntos
Neoplasias Ovarianas , Neoplasias Pancreáticas , Compostos de Fenilureia , Piridinas , Sarcoma , Timoma , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Monitoramento de Medicamentos/métodos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Timoma/tratamento farmacológico , Timoma/patologia , Resultado do Tratamento
7.
Ann Saudi Med ; 40(4): 273-280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32564624

RESUMO

In December 2019, a novel coronavirus was identified in patients in Wuhan, China. The virus, subsequently named severe acute respiratory syndrome coronavirus-2, spread worldwide and the disease (coronavirus disease 2019 or COVID-19) was declared a global pandemic by the World Health Organization in March 2020. Older adults and individuals with comorbidities have been reported as being more vulnerable to COVID-19. Patients with chronic liver disease (CLD) have compromised immune function due to cirrhosis and are more susceptible to infection. However, it is unclear if patients with CLD are more vulnerable to COVID-19 and its complications than other populations. The high number of severe cases of COVID-19 has placed an unusual burden on health systems, compromising their capacity to provide the regular care that patients with CLD require. Hence, it is incredibly crucial at this juncture to provide a set of interim recommendations on the management of patients with CLD during the current COVID-19 outbreak.


Assuntos
Infecções por Coronavirus/epidemiologia , Hepatopatias/epidemiologia , Pneumonia Viral/epidemiologia , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides/efeitos adversos , Alanina/efeitos adversos , Alanina/análogos & derivados , Amidas/efeitos adversos , Antivirais/uso terapêutico , Azetidinas/efeitos adversos , Betacoronavirus , Biópsia/métodos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Combinação de Medicamentos , Interações Medicamentosas , Inibidores Enzimáticos/efeitos adversos , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/terapia , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/terapia , Humanos , Hidroxicloroquina/efeitos adversos , Imunossupressores/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Cirrose Hepática/epidemiologia , Cirrose Hepática/terapia , Hepatopatias/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Lopinavir/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Pirazinas/efeitos adversos , Ritonavir/efeitos adversos , Arábia Saudita/epidemiologia , Sulfonamidas/efeitos adversos , Ultrassonografia/métodos
8.
N Engl J Med ; 382(26): 2493-2503, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579810

RESUMO

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Adulto , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina , Falha de Tratamento
9.
Infect Dis (Lond) ; 52(9): 659-661, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496938

RESUMO

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemólise , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Idoso , Azitromicina/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Transfusão de Sangue , Terapia de Substituição Renal Contínua , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Haptoglobinas/análise , Humanos , Hidroxicloroquina/uso terapêutico , Hipóxia/induzido quimicamente , Hipóxia/complicações , Masculino , Nasofaringe/virologia , Pandemias , Síndrome do Desconforto Respiratório do Adulto/complicações , Vírus da SARS/genética , Vírus da SARS/isolamento & purificação
10.
Arch Gerontol Geriatr ; 89: 104091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413690

RESUMO

INTRODUCTION: The neuroprotective effect of valproic acid has been observed in the animal models of neurodegeneration, which suggests it as a potential candidate for clinical trials. In this paper, we aimed to systematically analyze the efficacy and safety of valproic acid in the treatment of dementia. METHODS: We searched the electronic databases PubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge Infrastructure until March 2020 for the eligible randomized controlled trials, as well as the unpublished and ongoing trials. We pooled the results using a random-effects model. RESULTS: We included seven studies with 770 randomized patients with dementia, which compared valproic acid with placebo. Indeed, there were no significant differences found in the scores of Mini-mental State Examination, Cohen-Mansfield Agitation Inventory and number of patients with adverse events. Valproic acid is generally well-tolerated in patients with dementia, even in long-term therapy for 24 months. CONCLUSION: Insufficient evidences are found to support valproic acid in the treatment of dementia for cognitive, psychiatric symptoms or disease-modifying. The anticipations for a success in the trial of valproic acid for dementia in the future look not optimistic based on the available evidence.


Assuntos
Demência , Inibidores Enzimáticos , Ácido Valproico , Demência/tratamento farmacológico , Inibidores Enzimáticos/efeitos adversos , Humanos , Agitação Psicomotora , Ácido Valproico/efeitos adversos
11.
Am J Cardiol ; 128: 147-150, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32425199

RESUMO

Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure, and mortality have been reported with the use of these drugs. It is important to have knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.


Assuntos
Anti-Infecciosos/efeitos adversos , Betacoronavirus , Doenças Cardiovasculares/induzido quimicamente , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Anti-Infecciosos/administração & dosagem , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Combinação de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lopinavir/uso terapêutico , Pandemias , Ritonavir/uso terapêutico
12.
Medicine (Baltimore) ; 99(20): e20205, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443344

RESUMO

BACKGROUND: Autoimmune liver disease (ALD) is a chronic liver disease caused by immune dysfunction in the body. However, no causative or curative medical treatment with proven efficacy exists to cure ALDs, and liver transplantation (LT) remains the only effective treatment available. However, the problem of recurrence of ALDs (rALDs) still remains after LT, which seriously affects the survival rate of the patients. Therefore, clinicians need to be aware of the risk factors affecting rALDs after LT. Therefore, this meta-analysis aims to define the risk factors for rALDs, which include the recurrence of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. METHODS: A systematic search in Pubmed, Embase, Cochrane library and Web of Science databases was performed from 1980 to 2019. The inclusion criteria were risk factors for developing rALDs after LT. However, case series, case reports, reviews, meta-analysis and studies only including human immunodeficiency virus cases, children, and pregnant patients were excluded. RESULTS: The electronic database search yielded 1728 results. Sixty-three retrospective cohort studies met the inclusion criteria and 13 were included in the meta-analysis. The final cohort included 5077 patients, and among them, 21.96% developed rALDs. Colectomy before LT, HR 0.59 (95% confidence interval [CI]: 0.37-0.96), cholangiocarcinoma, HR 3.42 (95% CI: 1.88-6.21), multiple episodes of acute cellular rejection, HR 2.07 (95% CI: 1.27-3.37), model for end-stage liver disease score, HR 1.05 (95% CI: 1.02-1.08), use of mycophenolate mofetil, HR 1.46 (95% CI: 1.00-2.12) and the use of cyclosporin A, HR 0.69 (95% CI: 0.49-0.97) were associated with the risk of rprimary sclerosing cholangitis. In addition, the use of tacrolimus, HR 1.73 (95% CI: 1.00-2.99) and cyclosporin A, HR 0.59 (95% CI: 0.39-0.88) were associated with the risk of rALD. CONCLUSIONS: Multiple risk factors for rALDs were identified, such as colectomy before LT, cholangiocacinoma, multiple episodes of acute cellular rejection, model for end-stage liver disease score, and especially the use of mycophenolate mofetil, cyclosporin A and tacrolimus.


Assuntos
Colangite Esclerosante/etiologia , Hepatopatias/imunologia , Transplante de Fígado/efeitos adversos , Adulto , Inibidores de Calcineurina/efeitos adversos , Colangiocarcinoma/complicações , Colangite Esclerosante/induzido quimicamente , Colangite Esclerosante/epidemiologia , Colectomia/efeitos adversos , Colectomia/estatística & dados numéricos , Ciclosporina/efeitos adversos , Doença Hepática Terminal/complicações , Inibidores Enzimáticos/efeitos adversos , Feminino , Rejeição de Enxerto/complicações , Hepatite Autoimune/complicações , Hepatite Autoimune/epidemiologia , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/epidemiologia , Hepatopatias/etiologia , Hepatopatias/mortalidade , Hepatopatias/patologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tacrolimo/efeitos adversos
13.
Lancet Oncol ; 21(6): 796-807, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32416072

RESUMO

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. FINDINGS: Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8-10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6-4·2] vs 1·4 months [1·4-1·6]; hazard ratio 0·37; 95% CI 0·25-0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. INTERPRETATION: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. FUNDING: Agios Pharmaceuticals.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/administração & dosagem , Glicina/análogos & derivados , Isocitrato Desidrogenase/antagonistas & inibidores , Mutação , Piridinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Neoplasias dos Ductos Biliares/enzimologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/enzimologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Europa (Continente) , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Piridinas/efeitos adversos , República da Coreia , Fatores de Tempo , Estados Unidos
14.
Neurology ; 94(22): 959-969, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: covidwho-52532

RESUMO

The coronavirus 2019 (COVID-19) pandemic has potential to disproportionately and severely affect patients with neuromuscular disorders. In a short period of time, it has already caused reorganization of neuromuscular clinical care delivery and education, which will likely have lasting effects on the field. This article reviews (1) potential neuromuscular complications of COVID-19, (2) assessment and mitigation of COVID-19-related risk for patients with preexisting neuromuscular disease, (3) guidance for management of immunosuppressive and immunomodulatory therapies, (4) practical guidance regarding neuromuscular care delivery, telemedicine, and education, and (5) effect on neuromuscular research. We outline key unanswered clinical questions and highlight the need for team-based and interspecialty collaboration. Primary goals of clinical research during this time are to develop evidence-based best practices and to minimize morbidity and mortality related to COVID-19 for patients with neuromuscular disorders.


Assuntos
Infecções por Coronavirus/terapia , Imunossupressores/efeitos adversos , Doenças Neuromusculares/terapia , Pneumonia Viral/terapia , Antivirais/efeitos adversos , Cloroquina/efeitos adversos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/prevenção & controle , Assistência à Saúde , Desprescrições , Progressão da Doença , Desenvolvimento de Medicamentos , Inibidores Enzimáticos/efeitos adversos , Síndrome de Guillain-Barré/etiologia , Visita Domiciliar , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Infusões Subcutâneas , Macrolídeos/efeitos adversos , Doenças Musculares/etiologia , Miastenia Gravis/induzido quimicamente , Neurologia/educação , Doenças Neuromusculares/complicações , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Pesquisa , Comportamento de Redução do Risco , Autoadministração , Telemedicina , Vacinas Virais/uso terapêutico
15.
Cancer Chemother Pharmacol ; 85(5): 995-1001, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32318809

RESUMO

PURPOSE: Fedratinib, an oral, selective Janus kinase 2 inhibitor with activity against both wild-type and mutant Janus kinase 2, has pH-dependent solubility, with free solubility at pH 1. Concomitant administration of drugs that reduce gastric acid secretion, such as pantoprazole, may decrease the absorption of fedratinib and affect patient outcomes. The aim of this study was to evaluate the impact of 7-day repeated 40-mg doses of pantoprazole on the pharmacokinetic (PK) properties of a single 500-mg dose of fedratinib in healthy male subjects. METHODS: In this phase I, single-center, open-label, two-period, two-treatment, fixed-sequence crossover study, healthy male subjects were administered a single dose of fedratinib 500 mg on day 1 in Period 1, followed by pantoprazole 40 mg daily for 7 days (day 1 to day 7) and a single dose of fedratinib 500 mg on day 7 in Period 2. After the discontinuation of nine subjects due to vomiting, the protocol was amended to provide ondansetron as antiemetic prophylaxis to an additional ten enrolled subjects. RESULTS: Twenty-six subjects were included. Repeated doses of pantoprazole 40 mg resulted in clinically insignificant increases in fedratinib exposure. Maximum plasma concentration increased by 1.09-fold and area under the plasma concentration-time curve from time 0 to infinity increased by 1.15-fold. All treatment-emergent adverse events were mild or moderate, except for one instance of neutropenia, which was considered unrelated to study intervention. CONCLUSION: Coadministration with pantoprazole did not have clinically meaningful effects on fedratinib PK. No new or unexpected safety signals were observed with fedratinib.


Assuntos
Interações Medicamentosas , Janus Quinase 2/antagonistas & inibidores , Pantoprazol , Pirrolidinas , Sulfonamidas , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacocinética , Voluntários Saudáveis , Humanos , Masculino , Pantoprazol/administração & dosagem , Pantoprazol/efeitos adversos , Pantoprazol/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacocinética , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Pirrolidinas/farmacocinética , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacocinética , Resultado do Tratamento
16.
Neurology ; 94(22): 959-969, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32284362

RESUMO

The coronavirus 2019 (COVID-19) pandemic has potential to disproportionately and severely affect patients with neuromuscular disorders. In a short period of time, it has already caused reorganization of neuromuscular clinical care delivery and education, which will likely have lasting effects on the field. This article reviews (1) potential neuromuscular complications of COVID-19, (2) assessment and mitigation of COVID-19-related risk for patients with preexisting neuromuscular disease, (3) guidance for management of immunosuppressive and immunomodulatory therapies, (4) practical guidance regarding neuromuscular care delivery, telemedicine, and education, and (5) effect on neuromuscular research. We outline key unanswered clinical questions and highlight the need for team-based and interspecialty collaboration. Primary goals of clinical research during this time are to develop evidence-based best practices and to minimize morbidity and mortality related to COVID-19 for patients with neuromuscular disorders.


Assuntos
Infecções por Coronavirus/terapia , Imunossupressores/efeitos adversos , Doenças Neuromusculares/terapia , Pneumonia Viral/terapia , Antivirais/efeitos adversos , Cloroquina/efeitos adversos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/prevenção & controle , Assistência à Saúde , Desprescrições , Progressão da Doença , Desenvolvimento de Medicamentos , Inibidores Enzimáticos/efeitos adversos , Síndrome de Guillain-Barré/etiologia , Visita Domiciliar , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Infusões Subcutâneas , Macrolídeos/efeitos adversos , Doenças Musculares/etiologia , Miastenia Gravis/induzido quimicamente , Neurologia/educação , Doenças Neuromusculares/complicações , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Pesquisa , Comportamento de Redução do Risco , Autoadministração , Telemedicina , Vacinas Virais/uso terapêutico
17.
Libyan J Med ; 15(1): 1753943, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32281500

RESUMO

Knee Osteoarthritis is a considerable public health concern, both in terms of life quality and treatment financial impacts. To investigate this disease, animal models are deemed a promising alternative. In fact, although a perfect model is generally farfetched, the creation of models that simulate human disease as accurately as possible remains an important research stake. This study aims to highlight the usefulness of the model induced by injected Mono-Iodo-Acetate and to standardize it for the rabbit species. Osteoarthritis was induced by an infra-patellar injection of 0.2 ml of an MIA solution in the left knee of 24 female New Zealand rabbits. The right knee served as a control by receiving an injection of physiological serum. The rabbits were divided into 4 groups of 6 individuals each according to the dose of MIA received per knee. All rabbits were euthanized 30 days after the injection. After sacrifice, the knees were carefully dissected and macroscopic and microscopic scores of cartilage, meniscal and synovial lesions were attributed to each group. Our study followed the laboratory animal care and management guideline published in 2017 by the Canadian Council of Animal Care. The control knees of all rabbits showed no macroscopic or microscopic lesions. The macroscopic lesions: osteophytes, meniscal lesions, fibrillation and erosion of the cartilage and microscopic lesions: disorganization of the chondrocytes, decrease in proteoglycans and synovial inflammation clinically diagnosed in human pathology were all detected and were similarly reproducible among the knees of the same group. Through this work, we highlighted the merits of the arthritis model induced by MIA, namely its simulation of several aspects of human pathology. Further advantages are low cost, speed, reproducibility. This model notably avoids delicate and risky surgical operations.


Assuntos
Inibidores Enzimáticos/administração & dosagem , Ácido Iodoacético/administração & dosagem , Osteoartrite do Joelho/induzido quimicamente , Animais , Bolsa Sinovial/patologia , Bolsa Sinovial/ultraestrutura , Canadá/epidemiologia , Cartilagem/patologia , Cartilagem/ultraestrutura , Condrócitos/patologia , Modelos Animais de Doenças , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Injeções/métodos , Ácido Iodoacético/efeitos adversos , Menisco/patologia , Menisco/ultraestrutura , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/veterinária , Proteoglicanas/metabolismo , Coelhos , Reprodutibilidade dos Testes
18.
Lancet Haematol ; 7(4): e309-e319, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32145771

RESUMO

BACKGROUND: Mutations in isocitrate dehydrogenase-2 (IDH2) occur in around 5% of patients with myelodysplastic syndromes. Neomorphic activity of mutant IDH2 proteins results in hypermethylation of DNA and histones, leading to blocked haemopoietic differentiation. Enasidenib, an inhibitor of mutated IDH2 proteins, induces responses in patients with IDH2-mutated, relapsed or refractory acute myeloid leukaemia. We aimed to establish the clinical outcomes of enasidenib monotherapy in a subgroup of patients with myelodysplastic syndromes harbouring mutations in IDH2 from the AG221-C-001 trial. METHODS: The multicentre, open-label, phase 1-2 AG221-C-001 trial enrolled patients with advanced haematological malignancies (2008 WHO criteria) harbouring an IDH2 mutation. The present study is a subgroup analysis of patients with IDH2-mutated myelodysplastic syndromes in the phase 1 dose-escalation and expansion portions of the trial. Patients with myelodysplastic syndromes were aged 18 years or older with an ECOG performance status score of 2 or lower, and were relapsed or refractory to, or ineligible for, standard treatments. Patients received oral doses of enasidenib at 60-300 mg per day in repeated 28-day treatment cycles. In this subgroup analysis, we focused on the safety and activity of enasidenib as main outcomes. Overall response rate, duration of response, and overall and event-free survival analyses were by intention-to-treat. Safety was assessed in all participants who received at least one dose of study drug in terms of treatment-emergent adverse events. The AG221-C-001 trial is registered on ClinicalTrials.gov, NCT01915498, status ongoing but closed to recruitment. FINDINGS: 17 patients with myelodysplastic syndromes harbouring an IDH2 mutation (median age, 67·0 years [IQR 60·5-73·0]) were enrolled between Feb 18, 2014, and Sept 1, 2015. At data cutoff (Oct 1, 2018), after a median follow-up of 11·0 months (IQR 6·8-23·0), all patients had discontinued enasidenib, with a median of 3 treatment cycles (2-15) for all patients (five [29%] received ≥12 cycles). At entry, three (18%) patients had relapsed after allogeneic stem-cell transplants, 13 (76%) had previously received therapy with hypomethylating agents, and ten (59%) had received at least two previous therapies. No dose-limiting toxicities were reported. The most common treatment-emergent adverse events were diarrhoea and nausea (in nine [53%] patients each). Most common grade 3-4 treatment-emergent adverse events were indirect hyperbilirubinaemia (in six [35%] patients), pneumonia (in five [29%] patients), and thrombocytopaenia (in four [24%] patients). Serious treatment-emergent adverse events in more than one patient were pneumonia (in five [29% patients); tumor lysis syndrome (in three [18%] patients); and sepsis, atrial flutter, indirect hyperbilirubinaemia, cerebral hemorrhage, and mental status change (in two [12%] patients each). No treatment-related deaths occurred. An overall response was achieved in 9 patients (53% [95% CI 28-77]), with a median duration of response of 9·2 months (95% CI 1·0-not reached). Six (46%) of 13 patients previously treated with hypomethylating agents responded. Median overall survival was 16·9 months (95% CI 1·5-32·3), and median event-free survival was 11·0 months (1·5-16·7). INTERPRETATION: Enasidenib is generally well tolerated and can induce responses in patients with mutant IDH2 myelodysplastic syndromes, including in those who have had previous therapy with hypomethylating agents. Testing for IDH2 mutations in myelodysplastic syndromes is essential for identifying patients who might benefit from enasidenib therapy, including those patients in whom conventional treatments have been unsuccessful. FUNDING: Celgene and Agios Pharmaceuticals.


Assuntos
Aminopiridinas/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Isocitrato Desidrogenase/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Triazinas/uso terapêutico , Idoso , Aminopiridinas/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Hiperbilirrubinemia/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Polimorfismo de Nucleotídeo Único , Taxa de Sobrevida , Resultado do Tratamento , Triazinas/efeitos adversos
19.
Medicina (Kaunas) ; 56(2)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033501

RESUMO

BACKGROUND AND OBJECTIVES: This meta-analysis compared the efficacy and safety of peramivir compared to other neuraminidase inhibitors (NAIs). Materials and Methods: Data from PubMed, Embase, and Cochrane databases and ClinicalTrials.gov were searched until January 2019. Randomized controlled trials (RCTs) and observational studies (OSs) comparing peramivir with other NAIs for treating influenza were included. The Grading of Recommendations, Assessments, Development, and Evaluations (GRADE) system was used to judge the overall certainty of evidence; the result was moderate. The primary outcome was time to alleviation of symptoms. Twelve articles involving 2681 patients were included in this meta-analysis. We used a random-effect model to pool the effect size, which is expressed as the difference in means (MD), risk ratio (RR), and 95% confidence interval (CI). Results: Overall, peramivir was superior to other NAIs (MD = -11.214 hours, 95% CI: -19.119 to -3.310). The incidence of adverse events (RR = 1.023, 95% CI: 0.717 to 1.460) and serious adverse events (RR = 1.068, 95% CI: 0.702 to 1.625) in the peramivir group was similar to those in the oseltamivir group. In addition, peramivir had higher efficacy than each NAI alone. Conclusion: In conclusion, the efficacy of peramivir might be higher than that of other NAIs, and this agent is tolerated as well as other NAIs.


Assuntos
Antivirais/uso terapêutico , Ciclopentanos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Guanidinas/uso terapêutico , Influenza Humana/tratamento farmacológico , Neuraminidase/antagonistas & inibidores , Antivirais/efeitos adversos , Ciclopentanos/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Guanidinas/efeitos adversos , Humanos , Estudos Observacionais como Assunto , Oseltamivir/efeitos adversos , Oseltamivir/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Drug Discov Ther ; 14(1): 50-53, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32101820

RESUMO

Our earlier study investigated the incidence of severe abnormal behavior associated with neuraminidase inhibitors (NIs), but some studies have specifically examined the association of oseltamivir use and moderately abnormal behavior. Therefore, this study was undertaken to assess associations between moderately abnormal behavior and administered drugs. All cases of patients with influenza who exhibited moderately abnormal behavior were reported to us by physicians of all sentinel clinics and hospitals for influenza throughout Japan. Open Data of the National Database of Electronic Medical Claims include the numbers of patients diagnosed as having influenza who were prescribed NI. Incidence by NI was tested using Fisher's exact test. We received 518 moderately abnormal cases in 5-9-year-olds and 207 moderately abnormal behavior cases in 10-19-year-olds. The incidence among NI ranged from 193 per one million influenza patients in laninamivir among 10-19-year-olds to 1021 for peramivir among 5-9-year-olds. Estimation results revealed the order of risk among NIs as peramivir, oseltamivir, zanamivir and laninamivir in moderate abnormal behavior. Because of data limitations, risk among patients with and without NI cannot be compared.


Assuntos
Inibidores Enzimáticos/efeitos adversos , Comportamento de Doença/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Influenza Humana/psicologia , Neuraminidase/antagonistas & inibidores , Adolescente , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , Ciclopentanos/administração & dosagem , Ciclopentanos/efeitos adversos , Inibidores Enzimáticos/administração & dosagem , Guanidinas/administração & dosagem , Guanidinas/efeitos adversos , Humanos , Japão , Oseltamivir/administração & dosagem , Oseltamivir/efeitos adversos , Adulto Jovem , Zanamivir/administração & dosagem , Zanamivir/efeitos adversos , Zanamivir/análogos & derivados
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