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[PMID]:28463753
[Au] Autor:Walker A; Bergmann M; Camdereli J; Kaiser R; Lübke N; Timm J
[Ad] Endereço:Institute of Virology, Heinrich-Heine-University, University Hospital, Düsseldorf, Germany.
[Ti] Título:A genotype independent, full-genome reverse-transcription protocol for HCV genotyping and resistance testing.
[So] Source:J Clin Virol;91:42-48, 2017 06.
[Is] ISSN:1873-5967
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: HCV treatment options and cure rates have tremendously increased in the last decade. Although a pan-genotype HCV treatment has recently been approved, most DAA therapies are still genotype specific. Resistance-associated variants (RAVs) can limit the efficacy of DAA therapy and are associated with increased risk for therapy failure. With the approval of DAA regimens that recommend resistance testing prior to therapy, correct assessment of the genotype and testing for viruses with RAVs is clinically relevant. However, genotyping and resistance testing is generally done in costly and laborious separate reactions. OBJECTIVE: The aim of the study was to establish a genotype-independent full-genome reverse transcription protocol to generate a template for both genotyping and resistance testing and to implement it into our routine diagnostic setup. STUDY DESIGN: The complete HCV genome was reverse transcribed with a pan-genotype primer binding at the 3'end of the viral RNA. This cDNA served as template for transcription of the genotyping amplicon in the core region as well as for the resistance testing of NS3, NS5A, and NS5B. RESULTS: With the established RT-protocol the HCV core region was successfully amplified and genotyped from 124 out of 125 (99.2%) HCV-positive samples. The amplification efficiency of RAV containing regions in NS3, NS5A, NS5B was 96.2%, 96.6% and 94.4%, respectively. CONCLUSIONS: We developed a method for HCV full-genome cDNA synthesis and implemented it into a routine diagnostic setup. This cDNA can be used as template for genotyping amplicons covering the core or NS5B region as well as for resistance testing amplicons in NS3, NS5A and NS5B.
[Mh] Termos MeSH primário: Farmacorresistência Viral/genética
Genoma Viral/genética
Técnicas de Genotipagem
Hepacivirus/efeitos dos fármacos
Hepacivirus/genética
Transcrição Reversa
[Mh] Termos MeSH secundário: Antivirais/farmacologia
Antivirais/uso terapêutico
DNA Complementar
Genoma Viral/efeitos dos fármacos
Genótipo
Hepacivirus/isolamento & purificação
Hepatite C Crônica/sangue
Hepatite C Crônica/diagnóstico
Hepatite C Crônica/tratamento farmacológico
Seres Humanos
Reação em Cadeia da Polimerase
RNA Viral/sangue
RNA Viral/genética
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (DNA, Complementary); 0 (RNA, Viral)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29377953
[Au] Autor:Waduthantri S; Zhou L; Chee SP
[Ad] Endereço:Singapore Eye Research Institute, Singapore, Singapore.
[Ti] Título:Intra-cameral level of ganciclovir gel, 0.15% following topical application for cytomegalovirus anterior segment infection: A pilot study.
[So] Source:PLoS One;13(1):e0191850, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate the intra-cameral level of ganciclovir following topical application of ganciclovir gel, 0.15% for cytomegalovirus (CMV) anterior segment infection. DESIGN: Non-randomized, prospective, interventional clinical study. METHODS: Patients with active CMV anterior segment infection seen at Singapore National Eye Centre, confirmed by positive CMV real time PCR (RT-PCR) of the aqueous humor, that had not been treated with any form of ganciclovir in the preceding 1 month were recruited. They were treated with ganciclovir gel, 0.15% 1cc 5 times a day. Following 6 weeks of treatment, CMV load in the aqueous humor was measured using CMV RT-PCR and the ganciclovir drug levels in tears and aqueous humor were measured using high-performance liquid chromatography-mass spectrometry. The clinical features of the disease activity and the central corneal thickness (CCT) were recorded at the baseline and post-treatment. RESULTS: There were 29 eyes of 29 patients, of which 23 eyes had CMV anterior uveitis and 6 eyes had CMV endotheliitis. At the end of week 6, 26 eyes had undetectable CMV titre in the aqueous humor and no anterior chamber (AC) activity. Two patients had an increased CMV titre and increased AC inflammation. Both of these patients were non-compliant with the treatment. One patient had a reduced CMV titre in the aqueous humor with minimal AC inflammation. The mean ganciclovir concentration in the aqueous humor and the tears were 17.4 ± 30.6 ng/ml and 20,420.9 ± 33,120.8 ng/ml respectively. Mean CCT was 552.2 ± 42.3 microns. There was a weak correlation between the ganciclovir concentration in the aqueous humor and CCT (Spearmen's r = + 0.42, p = 0.025). There was no significant correlation between the ganiclovir concentration in the tears and CCT (Spearmen's r = + 0.39, p = 0.11). CONCLUSION: Ganciclovir levels in the aqueous humor was below the 50% inhibitory dose (ID50) for CMV replication, following topical application of the ganciclovir gel, 0.15%. TRIAL REGISTRATION: SingHealth Centralized Institutional Review Board, Singapore; R733/17/2010, ClinicalTrials.gov; NCT01647529.
[Mh] Termos MeSH primário: Segmento Anterior do Olho/patologia
Antivirais/administração & dosagem
Infecções por Citomegalovirus/tratamento farmacológico
Ganciclovir/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oftálmica
Adulto
Idoso
Idoso de 80 Anos ou mais
Cromatografia Líquida
Citomegalovirus/genética
Feminino
Seres Humanos
Masculino
Meia-Idade
Projetos Piloto
Estudos Prospectivos
Reação em Cadeia da Polimerase em Tempo Real
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:CLINICAL STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191850


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[PMID]:29268134
[Au] Autor:Plebanek E; Lescrinier E; Andrei G; Snoeck R; Herdewijn P; De Jonghe S
[Ad] Endereço:Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49 - bus 1041, 3000 Leuven, Belgium.
[Ti] Título:Emimycin and its nucleoside derivatives: Synthesis and antiviral activity.
[So] Source:Eur J Med Chem;144:93-103, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The synthesis of emimycin, 5-substituted emimycin analogues and the corresponding ribo- and 2'-deoxyribonucleoside derivatives is described. Emimycin, its 5-substituted congeners and the ribonucleoside derivatives are completely devoid of antiviral activity against RNA viruses. In contrast, some of the 2'-deoxyribosyl emimycin derivatives are potent inhibitors of the replication of herpes simplex virus-1 and varicella-zoster virus, lacking cytotoxicity.
[Mh] Termos MeSH primário: Antivirais/química
Antivirais/farmacologia
Nucleosídeos/química
Nucleosídeos/farmacologia
Pirazinas/química
Pirazinas/farmacologia
[Mh] Termos MeSH secundário: Antivirais/síntese química
Linhagem Celular
Herpes Simples/tratamento farmacológico
Herpesvirus Humano 1/efeitos dos fármacos
Herpesvirus Humano 1/fisiologia
Herpesvirus Humano 3/efeitos dos fármacos
Herpesvirus Humano 3/fisiologia
Seres Humanos
Nucleosídeos/síntese química
Pirazinas/síntese química
Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Nucleosides); 0 (Pyrazines); R14TE35LHD (emimycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:29262788
[Au] Autor:Brouard C; Boussac-Zarebska M; Silvain C; Durand J; de Lédinghen V; Pillonel J; Delarocque-Astagneau E
[Ad] Endereço:Santé publique France, the national public health agency, Saint-Maurice, France. cecile.brouard@santepubliquefrance.fr.
[Ti] Título:Rapid and large-scale implementation of HCV treatment advances in France, 2007-2015.
[So] Source:BMC Infect Dis;17(1):784, 2017 Dec 20.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014-2015. METHODS: Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks. RESULTS: Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014-2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined. CONCLUSIONS: Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Hepatite C Crônica
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
França/epidemiologia
Hepatite C Crônica/tratamento farmacológico
Hepatite C Crônica/epidemiologia
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2889-4


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[PMID]:28844981
[Au] Autor:Gogineni V; Hamann MT
[Ad] Endereço:Department of BioMolecular Sciences, Division of Medicinal Chemistry, School of Pharmacy, The University of Mississippi, University, MS, United States. Electronic address: vgoginen@go.olemiss.edu.
[Ti] Título:Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology.
[So] Source:Biochim Biophys Acta;1862(1):81-196, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability.
[Mh] Termos MeSH primário: Anti-Hipertensivos
Antineoplásicos
Antivirais
Organismos Aquáticos/química
Hipoglicemiantes
Biossíntese Peptídica
Peptídeos
[Mh] Termos MeSH secundário: Animais
Anti-Hipertensivos/química
Anti-Hipertensivos/uso terapêutico
Antineoplásicos/química
Antineoplásicos/uso terapêutico
Antivirais/química
Antivirais/uso terapêutico
Organismos Aquáticos/metabolismo
Seres Humanos
Hipoglicemiantes/química
Hipoglicemiantes/uso terapêutico
Peptídeos/química
Peptídeos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Antineoplastic Agents); 0 (Antiviral Agents); 0 (Hypoglycemic Agents); 0 (Peptides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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[PMID]:29458688
[Au] Autor:Mitchell SL; Chang YC; Feemster K; Cárdenas AM
[Ad] Endereço:1​Clinical Microbiology Laboratory, Children's Hospital of Pittsburgh of UPMC and Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
[Ti] Título:Implementation of a rapid influenza A/B and RSV direct molecular assay improves emergency department oseltamivir use in paediatric patients.
[So] Source:J Med Microbiol;67(3):358-363, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Influenza A virus (FluA), influenza B virus (FluB) and respiratory syncytial virus (RSV) illnesses increase hospitalizations during seasonal epidemics. METHODOLOGY: To determine the utility of the Simplexa FluA/B & RSV Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this assay to emergency department (ED) patients with influenza-like illness. RESULTS: Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours. Compared to the flu season prior to implementation of the Direct Flu/RSV, clinicians were more likely to prescribe 5 days of oseltamivir therapy for Direct Flu/RSV-positive patients in comparison to those with a negative test. CONCLUSIONS: Use of Direct Flu/RSV provides results rapidly, which leads to more appropriate use of oseltamivir. The ease of use of this assay and quick TAT allows for prompt decision-making, which is essential for patient care and effective disease control during the influenza season.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Influenza Humana/diagnóstico
Influenza Humana/tratamento farmacológico
Técnicas de Diagnóstico Molecular
Oseltamivir/uso terapêutico
Infecções por Vírus Respiratório Sincicial/diagnóstico
[Mh] Termos MeSH secundário: Antivirais/administração & dosagem
Criança
Saúde da Criança
Pré-Escolar
Serviço Hospitalar de Emergência
Feminino
Seres Humanos
Vírus da Influenza A/genética
Vírus da Influenza A/isolamento & purificação
Vírus da Influenza B/genética
Vírus da Influenza B/isolamento & purificação
Influenza Humana/virologia
Masculino
Nasofaringe/virologia
Oseltamivir/administração & dosagem
Kit de Reagentes para Diagnóstico
Reação em Cadeia da Polimerase em Tempo Real
Infecções por Vírus Respiratório Sincicial/virologia
Vírus Sinciciais Respiratórios/genética
Vírus Sinciciais Respiratórios/isolamento & purificação
Sensibilidade e Especificidade
Resultado do Tratamento
Viroses/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Reagent Kits, Diagnostic); 20O93L6F9H (Oseltamivir)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000676


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[PMID]:29458547
[Au] Autor:Growcott EJ; Bamba D; Galarneau JR; Leonard VHJ; Schul W; Stein D; Osborne CS
[Ad] Endereço:1​Novartis Institutes for Biomedical Research, Infectious Disease, Emeryville, CA, USA.
[Ti] Título:The effect of P38 MAP kinase inhibition in a mouse model of influenza.
[So] Source:J Med Microbiol;67(3):452-462, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Influenza viruses are a common cause of human respiratory infections, resulting in epidemics of high morbidity and mortality. We investigated the effect of a novel mitogen-activated protein kinase (MAPK) inhibitor in vitro and in a murine influenza model to further explore whether p38 MAPK inhibition could reduce viral replication. METHODS: In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38 MAPK inhibitor with an IC50 value of<1 µM, currently in clinical testing), dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection. Body weight, bronchoalveolar lavage cells, cytokines, total protein and lactate dehydrogenase as well as serum cytokines were measured; a subset of animals was evaluated histopathologically.Results/Key findings. p38MAP kinase inhibition with BCT194 had no impact on influenza replication in HBECs. When examining BCT197 in vivo, and comparing to vehicle-treated animals, reduced weight loss, improvement in survival and lack of impaired viral control was observed at BCT197 concentrations relevant to those being used in clinical trials of acute exacerbations of chronic obstructive pulmonary disease; at higher concentrations of BCT197 these effects were reduced. CONCLUSIONS: Compared to vehicle treatment, BCT197 (administered at a clinically relevant concentration) improved outcomes in a mouse model of influenza. This is encouraging given that the use of innate inflammatory pathway inhibitors may raise concerns of negative effects on infection regulation.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Inibidores Enzimáticos/farmacologia
Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos
Infecções por Orthomyxoviridae/virologia
Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antivirais/administração & dosagem
Antivirais/uso terapêutico
Brônquios/citologia
Linhagem Celular
Citocinas/sangue
Dexametasona/uso terapêutico
Modelos Animais de Doenças
Inibidores Enzimáticos/administração & dosagem
Inibidores Enzimáticos/uso terapêutico
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/virologia
Feminino
Seres Humanos
Vírus da Influenza A Subtipo H1N1/fisiologia
Influenza Humana/tratamento farmacológico
Influenza Humana/virologia
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/tratamento farmacológico
Oseltamivir/uso terapêutico
Resultado do Tratamento
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Cytokines); 0 (Enzyme Inhibitors); 20O93L6F9H (Oseltamivir); 7S5I7G3JQL (Dexamethasone); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000684


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[PMID]:29215337
[Au] Autor:Tütüncü EE; Güner R; Gürbüz Y; Kaya Kalem A; Öztürk B; Hasanoglu I; Sencan I; Tasyaran MA
[Ad] Endereço:Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey.
[Ti] Título:Adherence to Nucleoside/Nucleotide Analogue Treatment in Patients with Chronic Hepatitis B.
[So] Source:Balkan Med J;34(6):540-545, 2017 12 01.
[Is] ISSN:2146-3131
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Adherence to medication is an important aspect of preventing drug resistance and treatment failure in patients receiving nucleos(t)ide analogues for chronic hepatitis B. AIMS: To assess adherence to nucleoside/nucleotide analogues in chronic hepatitis B treatment and to determine factors associated with non-adherence. STUDY DESIGN: Cross-sectional study. METHODS: The study enrolled 85 chronic hepatitis B patients who had been receiving nucleoside/nucleotide analogues for ≥3 months. A questionnaire was completed by patients themselves, and adherence was evaluated based on patients' self-reporting. The use of at least 95% of the drugs in the previous month was considered as adequate adherence. RESULTS: Adherence was adequate in 82.4% of patients. Female gender (p=0.003), unemployment (p=0.041) and lower monthly family income (p=0.001) were related to lower adherence. Better adherence was significantly linked to adequate basic knowledge regarding chronic hepatitis B (p=0.049), longer treatment duration than 12 months (p<0.001), previous use of other medications for chronic hepatitis B (p=0.014) and regular follow-up by the same physician (p<0.001). CONCLUSION: Counselling patients about their disease state and the consequences of non-adherence is an important intervention for enhancing adherence. Naïve patients should be followed up more frequently to reinforce adherence.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Aconselhamento Diretivo/métodos
Alfabetização em Saúde/estatística & dados numéricos
Hepatite B Crônica/tratamento farmacológico
Adesão à Medicação/estatística & dados numéricos
Nucleosídeos/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos Transversais
Feminino
Conhecimentos, Atitudes e Prática em Saúde
Seres Humanos
Masculino
Meia-Idade
Fatores Socioeconômicos
Inquéritos e Questionários
Turquia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Nucleosides)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.4274/balkanmedj.2016.1461


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[PMID]:29386460
[Au] Autor:Shuto S
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Hokkaido University.
[Ti] Título:Foreword.
[So] Source:Chem Pharm Bull (Tokyo);66(2):116, 2018.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Antivirais/farmacologia
Nucleosídeos/farmacologia
Nucleotídeos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Antivirais/síntese química
Antivirais/química
Pesquisa Biomédica
Química Farmacêutica
Sistemas de Liberação de Medicamentos
Seres Humanos
Nucleosídeos/síntese química
Nucleosídeos/química
Nucleotídeos/síntese química
Nucleotídeos/química
[Pt] Tipo de publicação:INTRODUCTORY JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antiviral Agents); 0 (Nucleosides); 0 (Nucleotides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c18-ctf6602


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[PMID]:29211658
[Au] Autor:Marty FM; Ljungman P; Chemaly RF; Maertens J; Dadwal SS; Duarte RF; Haider S; Ullmann AJ; Katayama Y; Brown J; Mullane KM; Boeckh M; Blumberg EA; Einsele H; Snydman DR; Kanda Y; DiNubile MJ; Teal VL; Wan H; Murata Y; Kartsonis NA; Leavitt RY; Badshah C
[Ad] Endereço:From the Dana-Farber Cancer Institute and Brigham and Women's Hospital (F.M.M.) and Tufts Medical Center and Tufts University School of Medicine (D.R.S.), Boston; Karolinska University Hospital and Karolinska Institutet, Stockholm (P.L.); University of Texas M.D. Anderson Cancer Center, Houston (R.F
[Ti] Título:Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.
[So] Source:N Engl J Med;377(25):2433-2444, 2017 12 21.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV-terminase complex. METHODS: In this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk. Letermovir was administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). Patients in whom clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) developed discontinued the trial regimen and received anti-CMV treatment. The primary end point was the proportion of patients, among patients without detectable CMV DNA at randomization, who had clinically significant CMV infection through week 24 after transplantation. Patients who discontinued the trial or had missing end-point data at week 24 were imputed as having a primary end-point event. Patients were followed through week 48 after transplantation. RESULTS: From June 2014 to March 2016, a total of 565 patients underwent randomization and received letermovir or placebo beginning a median of 9 days after transplantation. Among 495 patients with undetectable CMV DNA at randomization, fewer patients in the letermovir group than in the placebo group had clinically significant CMV infection or were imputed as having a primary end-point event by week 24 after transplantation (122 of 325 patients [37.5%] vs. 103 of 170 [60.6%], P<0.001). The frequency and severity of adverse events were similar in the two groups overall. Vomiting was reported in 18.5% of the patients who received letermovir and in 13.5% of those who received placebo; edema in 14.5% and 9.4%, respectively; and atrial fibrillation or flutter in 4.6% and 1.0%, respectively. The rates of myelotoxic and nephrotoxic events were similar in the letermovir group and the placebo group. All-cause mortality at week 48 after transplantation was 20.9% among letermovir recipients and 25.5% among placebo recipients. CONCLUSIONS: Letermovir prophylaxis resulted in a significantly lower risk of clinically significant CMV infection than placebo. Adverse events with letermovir were mainly of low grade. (Funded by Merck; ClinicalTrials.gov number, NCT02137772 ; EudraCT number, 2013-003831-31 .).
[Mh] Termos MeSH primário: Acetatos/uso terapêutico
Antivirais/uso terapêutico
Infecções por Citomegalovirus/prevenção & controle
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Quinazolinas/uso terapêutico
[Mh] Termos MeSH secundário: Acetatos/efeitos adversos
Adolescente
Adulto
Idoso
Antivirais/efeitos adversos
Citomegalovirus/genética
Citomegalovirus/isolamento & purificação
Infecções por Citomegalovirus/epidemiologia
Infecções por Citomegalovirus/etiologia
DNA Viral/sangue
Método Duplo-Cego
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Quinazolinas/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIC246); 0 (Acetates); 0 (Antiviral Agents); 0 (DNA, Viral); 0 (Quinazolines)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171207
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1706640



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