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[PMID]:29318278
[Au] Autor:Atri A; Frölich L; Ballard C; Tariot PN; Molinuevo JL; Boneva N; Windfeld K; Raket LL; Cummings JL
[Ad] Endereço:Ray Dolby Brain Health Center, California Pacific Medical Center, San Francisco.
[Ti] Título:Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.
[So] Source:JAMA;319(2):130-142, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: New therapeutic approaches for Alzheimer disease (AD) are needed. Objective: To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Design, Setting, and Participants: Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Interventions: Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Main Outcomes and Measures: Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Results: Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0.53 for the 10-mg dose group, and 0.56 for the placebo group (adjusted mean difference vs placebo, 0.63 [95% CI, -0.38 to 1.65] for the 30-mg dose group; given the gated testing strategy and the null findings at the 30-mg dose, statistical comparison of the 10-mg dose was not performed). In study 3, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.38 for the 60-mg dose of idalopirdine group and 0.82 for the placebo group (adjusted mean difference vs placebo, -0.55 [95% CI, -1.45 to 0.36]). Treatment-emergent adverse events occurred in between 55.4% and 69.7% of participants in the idalopirdine groups vs between 56.7% and 61.4% of participants in the placebo groups. Conclusions and Relevance: In patients with mild to moderate AD, the use of idalopirdine compared with placebo did not improve cognition over 24 weeks of treatment. These findings do not support the use of idalopirdine for the treatment of AD. Trial Registration: clinicaltrials.gov Identifiers: NCT01955161, NCT02006641, and NCT02006654.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Benzilaminas/uso terapêutico
Inibidores da Colinesterase/uso terapêutico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Acidentes por Quedas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Benzilaminas/administração & dosagem
Benzilaminas/efeitos adversos
Inibidores da Colinesterase/efeitos adversos
Cognição/efeitos dos fármacos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indóis/administração & dosagem
Indóis/efeitos adversos
Masculino
Meia-Idade
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Indoles); 0 (Piperidines); 0 (Serotonin Antagonists); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20373


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[PMID]:29345156
[Au] Autor:Svetel M; Tomic A; Kresojevic N; Kostic V
[Ad] Endereço:a Clinic of Neurology, Clinical Center of Serbia, Faculty of Medicine , University of Belgrade , Belgrade , Serbia.
[Ti] Título:Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson's disease.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):353-360, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa treated patients with PD and motor fluctuations. Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert commentary: Oral OPC exhibits linear, dose-dependent absorption. However, following concomitant ingestion of a high-fat, high-calorie meal, the maximum plasma concentration will be decreased. A once-daily bedtime administration of OPC 1 h after the last daily L-Dopa/AADCi, are considered to avoid any interaction during the L-Dopa absorption phase. There are no clinically relevant effects of age (in adults), renal impairment or race on the pharmacokinetics of OPC. OPC dose adjustment is not needed in patients with mild to moderate chronic hepatic impairment. Opicapone exhibits the lowest potential for cytotoxicity in comparison with other COMT inhibitors. It significantly decreases COMT activity, with half-life of COMT inhibition in human erythrocytes of 61.6 h and increases systemic exposure to L-Dopa. This provides an enhancement in L-Dopa availability that translates into clinical benefit for PD patients in terms of significant decrease of OFF periods and increase in ON-time without troublesome dyskinesia.
[Mh] Termos MeSH primário: Antiparkinsonianos/administração & dosagem
Oxidiazóis/administração & dosagem
Doença de Parkinson/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Animais
Antiparkinsonianos/efeitos adversos
Antiparkinsonianos/farmacocinética
Inibidores de Catecol O-Metiltransferase/administração & dosagem
Inibidores de Catecol O-Metiltransferase/farmacocinética
Relação Dose-Resposta a Droga
Quimioterapia Combinada
Interações Alimento-Droga
Meia-Vida
Seres Humanos
Levodopa/administração & dosagem
Levodopa/farmacocinética
Oxidiazóis/efeitos adversos
Oxidiazóis/farmacocinética
Doença de Parkinson/fisiopatologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Catechol O-Methyltransferase Inhibitors); 0 (Oxadiazoles); 46627O600J (Levodopa); Y5929UIJ5N (opicapone)
[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:180119
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1430138


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[PMID]:29338536
[Au] Autor:Kupka D; Sibbing D
[Ad] Endereço:a Department of Cardiology , LMU München , Munich , Germany.
[Ti] Título:P2Y receptor inhibitors: an evolution in drug design to prevent arterial thrombosis.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):303-315, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: P2Y12 inhibitors are a critical component of dual antiplatelet therapy (DAPT), which is the superior strategy to prevent arterialthrombosis in patients with acute coronary syndromes (ACS) and undergoing stent implantation.. Areas covered: Basic science articles, clinical studies, and reviews from 1992-2017 were searched using Pubmed library to collet impactful literature. After an introduction to the purinergic receptor biology, this review summarizes current knowledge on P2Y12 receptor inhibitors. Furthermore, we describe the subsequent improvements of next-generation P2Y12 receptor inhibitors facing the ambivalent problem of bleeding events versus prevention of arterial thrombosis in a variety of clinical settings. Therefore, we summarize data from relevant preclinical and clinical trials of currently approved P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor) and provide strategies of drug switching and management of bleeding events. Expert opinion: An enormous amount of pharmacologic and clinical data is available for the application of P2Y12 receptor inhibitors. Today prasugrel, ticagrelor and clopidogrel are the standard of care drugs during dual antiplatelet therapy for ACS patients, but have considerable rates of bleeding. Recent and future clinical trials will provide evidence for subsequent escalation and de-escalation strategies of P2Y12 receptor inhibition. These data may pave the way for an evidence-based, individualized P2Y12 receptor inhibitor therapy.
[Mh] Termos MeSH primário: Desenho de Drogas
Antagonistas do Receptor Purinérgico P2Y/farmacologia
Trombose/prevenção & controle
[Mh] Termos MeSH secundário: Síndrome Coronariana Aguda/complicações
Síndrome Coronariana Aguda/tratamento farmacológico
Animais
Quimioterapia Combinada
Hemorragia/induzido quimicamente
Hemorragia/epidemiologia
Seres Humanos
Inibidores da Agregação de Plaquetas/administração & dosagem
Inibidores da Agregação de Plaquetas/efeitos adversos
Inibidores da Agregação de Plaquetas/farmacologia
Antagonistas do Receptor Purinérgico P2Y/administração & dosagem
Antagonistas do Receptor Purinérgico P2Y/efeitos adversos
Trombose/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Platelet Aggregation Inhibitors); 0 (Purinergic P2Y Receptor Antagonists)
[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:180118
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1428557


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[PMID]:29214785
[Au] Autor:Jang H; Kim KY; Kim DS
[Ad] Endereço:Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.
[Ti] Título:Clinical Outcomes of Low-Dose Methotrexate Therapy as a Second-Line Drug for Intravenous Immunoglobulin-Resistant Kawasaki Disease.
[So] Source:Yonsei Med J;59(1):113-118, 2018 Jan.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.
[Mh] Termos MeSH primário: Imunoglobulinas Intravenosas/uso terapêutico
Metotrexato/uso terapêutico
Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico
[Mh] Termos MeSH secundário: Proteína C-Reativa/análise
Criança
Pré-Escolar
Vasos Coronários/patologia
Demografia
Relação Dose-Resposta a Droga
Quimioterapia Combinada
Feminino
Seres Humanos
Lactente
Masculino
Metotrexato/administração & dosagem
Síndrome de Linfonodos Mucocutâneos/sangue
Estudos Retrospectivos
Esteroides/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunoglobulins, Intravenous); 0 (Steroids); 9007-41-4 (C-Reactive Protein); YL5FZ2Y5U1 (Methotrexate)
[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:171208
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2018.59.1.113


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[PMID]:29441974
[Au] Autor:Gudienè V
[Ti] Título:The medical treatment of Maria, Dowager Empress of the Russian Empire: an analysis of her prescription book from 1807 and 1808.
[So] Source:Pharmazie;71(11):670-679, 2016 Nov 02.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:This study analyzes the medicines that were used to treat the Dowager Russian Empress Maria, widow of Tsar Paul I, and describes the doctors who cared for her health in 1807 and 1808. The source for this research was the imperial court pharmacy prescription book 1807-1811. Hypotheses about the diseases and medical problems of the Empress and how treatment for her differed according to circumstances, particularly after the loss of her granddaughter Princess Elizabeth, have been made based on the prescriptions recorded in the book. The content of the prescriptions suggests that the Empress suffered from gastrointestinal tract disorders, skin and eye diseases, neuralgic pains and insomnia. Foreign physicians educated in European universities worked at the imperial court and implemented European medical traditions. They took high positions in the administration and the medical education system, and gradually spread their experience and modern knowledge to Tsarist Russian society.
[Mh] Termos MeSH primário: Prescrições de Medicamentos/história
Tratamento Farmacológico/história
[Mh] Termos MeSH secundário: Livros
Quimioterapia Combinada
História do Século XIX
Farmácias
Médicos
Federação Russa
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6067


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[PMID]:29203734
[Au] Autor:Skochko OV; Kaidashev IP
[Ad] Endereço:Department Of Internal Medicine No 3 With Phthisiology, Higher State Educational Establishment Of Ukraine "Ukrainian Medical Stomatological Academy", Poltava, Ukraine.
[Ti] Título:Effect of pioglitazone on insulin resistance, progression of atherosclerosis and clinical course of coronary heart disease.
[So] Source:Wiad Lek;70(5):881-890, 2017.
[Is] ISSN:0043-5147
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues. THE AIM: Our aim was to study the effect of pioglitazone on insulin resistance, the clinical course of atherosclerosis and coronary heart disease (CHD). MATERIALS AND METHODS: The study included 43 patients with coronary artery disease. Patients were divided into the main group - 20 patients, in whom pioglitazone (Pioglar, Ranbaxy, India) was included in the combined therapy at a dose of 15 mg 1 time per day in the morning, and the comparison group - 23 patients receiving standard complex drug therapy over 6 months. Patients underwent clinical examination, ultrasound of neck vessels, study of carbohydrate and lipid metabolism. RESULTS: Joining pioglitazone to standard therapy resulted in the reduction of systolic (p<0.05) and diastolic (p<0.05) blood pressure; decrease in the duration of pain attacks (p<0.05); reduction in the frequency of angina attacks (p<0.05); regression of atherosclerosis of the carotid vessels (p<0.05), decrease in the thickness of the intima-media complex (p<0.05). The decline in oral glucose tolerance test (p<0.05), hyperglycemic factor (p<0.05), total cholesterol (p<0.05), and low density lipoproteins (p<0.05) were observed, as well as increased high-density lipoprotein (p<0.05). CONCLUSION: Long-term treatment with pioglitazone at low doses against the background of standard therapy contributes to functional and clinical condition of patients, promotes the prevention of atherosclerosis and reduction of insulin resistance, thereby improving the clinical manifestations of coronary heart disease.
[Mh] Termos MeSH primário: Aterosclerose/tratamento farmacológico
Hipoglicemiantes/administração & dosagem
Resistência à Insulina
Tiazolidinedionas/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Aterosclerose/diagnóstico por imagem
Fármacos Cardiovasculares/administração & dosagem
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Meia-Idade
Resultado do Tratamento
Ultrassonografia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Hypoglycemic Agents); 0 (Thiazolidinediones); X4OV71U42S (pioglitazone)
[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:171206
[St] Status:MEDLINE


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[PMID]:28471102
[Au] Autor:Yoo SG; Cho MJ; Kim US; Baek SH
[Ad] Endereço:Department of Ophthalmology, Kim's Eye Hospital, Seoul, Korea.
[Ti] Título:Cycloplegic Refraction in Hyperopic Children: Effectiveness of a 0.5% Tropicamide and 0.5% Phenylephrine Addition to 1% Cyclopentolate Regimen.
[So] Source:Korean J Ophthalmol;31(3):249-256, 2017 Jun.
[Is] ISSN:2092-9382
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To evaluate the effectiveness of a cycloplegic regimen using 0.5% tropicamide and 0.5% phenylephrine (Tropherine, Hanmi Pharm), in addition to 1% cyclopentolate, in hyperopic children. METHODS: The medical records of hyperopic patients below the age of 14 years who had undergone cycloplegic retinoscopy were retrospectively reviewed. Cycloplegic refractions were performed using one of two cycloplegic regimens. Regimen 1 was a Tropherine-added regimen comprising the administration of one drop of 1% cyclopentolate followed by two to three drops of Tropherine added at 15-minute intervals. Regimen 2 was a cyclopentolate-only regimen comprising the administration of three to four drops of 1% cyclopentolate at 15-minute intervals. The mean difference between noncycloplegic and cycloplegic refraction was compared between the two regimens. RESULTS: A total of 308 eyes of 308 hyperopic children were included. The mean difference (±standard deviation) in the spherical equivalent (SE) between cycloplegic and noncycloplegic refraction was significantly larger in regimen 2 than in regimen 1, with values of +1.70 ± 1.03 diopters (D) and +1.25 ± 0.89 D, respectively (p=0.001). The SE change after cycloplegia was significantly different between the two regimens only in patients aged 5 years or younger (p=0.001), particularly in those with high hyperopia with an SE ≥5 D (p=0.005) or fully accommodative esotropia (p=0.009). There was no significant difference between the two regimens in patients older than 5 years, regardless of the presence of high hyperopia or fully accommodative esotropia. CONCLUSIONS: The Tropherine-added regimen exerted a weaker cycloplegic effect than the cyclopentolate-only regimen, particularly in children under the age of 5 years with high hyperopia or fully accommodative esotropia. However, the difference in refraction between the two regimens was small. A Tropherine-added regimen can be effective in hyperopic children, with less associated discomfort than the instillation of cyclopentolate.
[Mh] Termos MeSH primário: Acomodação Ocular/efeitos dos fármacos
Ciclopentolato/administração & dosagem
Oftalmopatias Hereditárias/tratamento farmacológico
Hiperopia/tratamento farmacológico
Fenilefrina/administração & dosagem
Refração Ocular/efeitos dos fármacos
Tropicamida/administração & dosagem
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Quimioterapia Combinada
Oftalmopatias Hereditárias/fisiopatologia
Feminino
Seguimentos
Seres Humanos
Hiperopia/fisiopatologia
Lactente
Recém-Nascido
Masculino
Midriáticos/administração & dosagem
Soluções Oftálmicas/administração & dosagem
Estudos Retrospectivos
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mydriatics); 0 (Ophthalmic Solutions); 1WS297W6MV (Phenylephrine); I76F4SHP7J (Cyclopentolate); N0A3Z5XTC6 (Tropicamide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.3341/kjo.2016.0007


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[PMID]:28460112
[Au] Autor:Aponte S; Guerra ÁP; Álvarez-Larrotta C; Bernal SD; Restrepo C; González C; Yasnot MF; Knudson-Ospina A
[Ad] Endereço:Grupo de Bioquímica y Biología Celular, Instituto Nacional de Salud, Bogotá, D.C., Colombia.
[Ti] Título:Baseline in vivo, ex vivo and molecular responses of Plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in Colombia.
[So] Source:Trans R Soc Trop Med Hyg;111(2):71-80, 2017 02 01.
[Is] ISSN:1878-3503
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed. Results: From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found. Conclusion: This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Artemisininas/uso terapêutico
Etanolaminas/uso terapêutico
Fluorenos/uso terapêutico
Malária/tratamento farmacológico
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Antimaláricos/farmacologia
Artemisininas/farmacologia
Criança
Colômbia
Variações do Número de Cópias de DNA
Combinação de Medicamentos
Resistência a Medicamentos/efeitos dos fármacos
Resistência a Medicamentos/genética
Quimioterapia Combinada
Etanolaminas/farmacologia
Feminino
Fluorenos/farmacologia
Seres Humanos
Malária/parasitologia
Masculino
Meia-Idade
Parasitemia/tratamento farmacológico
Plasmodium falciparum/isolamento & purificação
Polimorfismo Genético
Proteínas de Protozoários/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (Protozoan Proteins); 0 (artemether-lumefantrine combination); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/trstmh/trx021


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[PMID]:28460083
[Au] Autor:Rendas-Baum R; Kosinski M; Singh A; Mebus CA; Wilkinson BE; Wallenstein GV
[Ad] Endereço:QualityMetric Incorporated Lincoln, RI.
[Ti] Título:Estimated medical expenditure and risk of job loss among rheumatoid arthritis patients undergoing tofacitinib treatment: post hoc analyses of two randomized clinical trials.
[So] Source:Rheumatology (Oxford);56(8):1386-1394, 2017 Aug 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Methods: Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. Results: MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P < 0.001); >20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾16%, and risk of future job loss decreased ∼20% (P < 0.001 vs placebo). MME reduction by month 3 was $70 greater for tofacitinib- than placebo-treated MTX inadequate responders (P < 0.001); ⩾23 and 13% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾31% and risk of future job loss decreased ⩾25% (P < 0.001 vs placebo). Conclusion: Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi.
[Mh] Termos MeSH primário: Antirreumáticos/economia
Artrite Reumatoide/economia
Efeitos Psicossociais da Doença
Gastos em Saúde
Piperidinas/economia
Pirimidinas/economia
Pirróis/economia
Retorno ao Trabalho/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adalimumab/administração & dosagem
Adalimumab/economia
Adulto
Antirreumáticos/administração & dosagem
Artrite Reumatoide/tratamento farmacológico
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Metotrexato/administração & dosagem
Metotrexato/economia
Meia-Idade
Piperidinas/administração & dosagem
Pirimidinas/administração & dosagem
Pirróis/administração & dosagem
Fatores de Risco
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antirheumatic Agents); 0 (Piperidines); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib); FYS6T7F842 (Adalimumab); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex087


  10 / 153389 MEDLINE  
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[PMID]:27778642
[Au] Autor:Garibay-Nieto N; Queipo-García G; Alvarez F; Bustos M; Villanueva E; Ramírez F; León M; Laresgoiti-Servitje E; Duggirala R; Macías T; Cuevas S; Jalife A; Fonseca-Sánchez M; Serratos F; López-Alvarenga JC
[Ad] Endereço:Children and Adolescent Obesity Clinic.
[Ti] Título:Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial.
[So] Source:J Clin Endocrinol Metab;102(1):132-140, 2017 Jan 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary. Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity. Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo. Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group. Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/prevenção & controle
Hipoglicemiantes/uso terapêutico
Resistência à Insulina
Ácidos Linoleicos Conjugados/uso terapêutico
Síndrome Metabólica/prevenção & controle
Metformina/uso terapêutico
Obesidade/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores/análise
Glicemia/análise
Composição Corporal
Criança
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Insulina/sangue
Lipídeos/análise
Masculino
Obesidade/complicações
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Glucose); 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Linoleic Acids, Conjugated); 0 (Lipids); 9100L32L2N (Metformin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2701



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