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1.
Mem Inst Oswaldo Cruz ; 116: e200603, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495083

RESUMO

BACKGROUND: In March 2020, the World Health Organization (WHO) launched the Solidarity Program, probably the largest global initiative to encourage and support research in four promising drugs, named Remdesivir, Hydroxychloroquine, ß Interferon and the combination Lopinavir / Ritonavir, to reduce the mortality of Coronavirus disease 2019 (COVID-19). OBJECTIVES: Considering the potential impact of Solidarity Program to restrain the current pandemic, the present study aims to investigate whether it was designed upon indicators of scientific productivity, defined as the level of the production of new scientific knowledge and of the institutional capabilities, estimated in terms of scientific publications and technological agreements. METHODS: The scientific documents on Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Coronavirus were retrieved from Scopus database while the technological agreements on coronavirus were obtained through Cortellis. As for the institutions and countries, we have considered the data on author's affiliations in both set of data. For comparison, we included the analysis of documents related with other drugs or therapies, such as vaccines and antibodies, which were listed in a Clarivate's report on coronaviruses research. FINDINGS: Most of the analysis refers to documents on Coronavirus, the largest group. The number of documents related to WHO's drugs are almost five times higher than in the other groups. This subset of documents involves the largest and most diverse number of institutions and countries. As for agreements, we observed a smaller number of institutions involved in it, suggesting differences between countries in terms of technical and human capabilities to develop basic and/or clinical research on coronavirus and to develop new forms or products to treat or to prevent the disease. MAIN CONCLUSIONS: Hence, the results shown in this study illustrate that decisions taken by an international scientific body, as WHO, were mainly based in scientific knowledge and institutional competencies.


Assuntos
Antivirais , COVID-19 , Antivirais/uso terapêutico , Combinação de Medicamentos , Humanos , SARS-CoV-2 , Organização Mundial da Saúde
3.
AIDS Res Ther ; 18(1): 57, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488812

RESUMO

INTRODUCTION: Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations. METHODS: Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients. RESULTS: Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4-16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27-2.88), abacavir-lamivudine-atazanavir (1.58; 1.08-2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07-1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54-0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir. CONCLUSION: The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Infarto do Miocárdio , Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Lamivudina/uso terapêutico , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Tenofovir/efeitos adversos , Estados Unidos/epidemiologia
4.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4193-4200, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467732

RESUMO

As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.


Assuntos
Medicamentos de Ervas Chinesas , Endotoxemia , Animais , Combinação de Medicamentos , Endotoxemia/tratamento farmacológico , Ratos
5.
J Assoc Physicians India ; 69(4): 11-12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34470194

RESUMO

For decades, short acting beta agonists (SABAs) have been prescribed for giving symptomatic relief to asthmatics. However, this symptomatic benefit perceived by the patient leads to the overuse and dependency of the patient to the SABA inhaler and underusage of the inhaled corticosteroid (ICS) containing controller inhalers resulting in destabilizing disease control and increased risk of exacerbations. In order to address this issue, the 2019 update of the Global Initiative for Asthma (GINA) strategy document no longer recommends the use of SABA inhalers as the preferred reliever for asthma due to concerns around poor outcomes and safety. Instead, it strongly supports the use of a combined ICS-fast acting beta agonist as a reliever also termed as an Anti-inflammatory Reliever Therapy (AIR). In this review we discuss the extent of SABA overusage and its impact on asthma outcomes, the resultant change in the recommendations in the GINA document and finally the evidence supporting the use of formoterol- budesonide as AIR therapy.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Budesonida/uso terapêutico , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Humanos , Nebulizadores e Vaporizadores
6.
Intern Med ; 60(17): 2807-2809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470986

RESUMO

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.


Assuntos
Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Insuficiência Renal Crônica , Idoso , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Japão , Masculino , Neprilisina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Volume Sistólico , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico
7.
J Med Microbiol ; 70(9)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491156

RESUMO

Introduction. The increase of invasive fungal infections (IFIs) and associated treatment failure in populations at risk is driving us to look for new treatments.Hypothesis. The CIN-102 compound, derived from cinnamon essential oil, could be a new antifungal class with an activity, in particular, on strains resistant to current antifungals but also on biofilms, a factor of virulence and resistance of fungi.Aim. The aim of this study is to show the activity of CIN-102 on various strains resistant to current antifungals, on the biofilm and to determine the possibility of resistance induced with this compound.Methodology. We studied the MIC of CIN-102 and of current antifungals (voriconazole and amphotericin B) using CLSI techniques against eight different strains of three genera of filamentous fungi involved in IFIs and having resistance phenotypes to current antifungals. We also determined their effects on biofilm formation, and the induced resistance by voriconazole (VRC) and CIN-102.Results. MIC values determined for CIN-102 were between 62.5 and 250 µg ml-1. We demonstrated the antifungal effect of CIN-102 on biofilm, and more particularly on its formation, with 100 % inhibition achieved for most of the strains. CIN-102 at a sub-inhibitory concentration in the medium did not induce resistance in our strains, even after 30 generations.Conclusions. In this study we show that CIN-102 is effective against resistant filamentous fungi and against biofilm formation. In addition, our strains did not acquire a resistance phenotype against CIN-102 over time, unlike with VRC. CIN-102 is therefore an interesting candidate for the treatment of IFIs, including in cases of therapeutic failure linked to resistance, although further studies on its efficacy, safety and mechanism of action are needed.


Assuntos
Antifúngicos/farmacologia , Benzoatos/farmacologia , Biofilmes/efeitos dos fármacos , Cinamatos/farmacologia , Fungos/efeitos dos fármacos , Micoses , Terpenos/farmacologia , Anfotericina B/farmacologia , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Micoses/microbiologia , Voriconazol/farmacologia
8.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3998-4007, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472277

RESUMO

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.


Assuntos
Medicamentos de Ervas Chinesas , Doença Cardiopulmonar , Combinação de Medicamentos , Humanos , Revisões Sistemáticas como Assunto
9.
Ann Palliat Med ; 10(8): 8684-8691, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488357

RESUMO

BACKGROUND: The aim of this study was to observe the effect of Sacubitril/Valsartan on cardiac function and remodeling in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 120 patients with HFrEF were selected and given standard heart failure treatment according to the 2017 ACC/AHA/HFSA guidelines. Regardless of whether patients had taken Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers (ACEI/ARB) medications previously, after admission they were treated with the minimum effective dose of Sacubitril/Valsartan according to their blood pressure reading. Baseline clinical data were recorded and patients were followed up at 1, 3, 6, 9, and 12 months post discharge, during which time the dose of Sacubitril/Valsartan was gradually increased to the maximum tolerated dose (dose range 25-200 mg/twice daily). During follow-up, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), and left atrium diameter (LAD) were monitored; a 6-minute walking test and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were recorded; and adverse reactions were collected. RESULTS: Over the course of the 12-month follow-up, the plasma concentrations of NT-proBNP were significantly reduced compared with the baseline, and the longer the follow-up time, the lower the NT-proBNP levels were (P<0.05). Similarly, LVEDD, LVESD and LAD were significantly smaller at 12 months than at baseline, and the longer the follow-up time, the smaller the internal diameter was (P<0.05). The LVEF, 6-minute walking distance and KCCQ scores increased significantly from baseline (P<0.05), whereas eGFR and serum potassium levels showed no significant change compared with the baseline. CONCLUSIONS: Sacubitril/Valsartan demonstrated a remarkable ability to improve cardiac function and to control cardiac remodeling with a high degree of safety in patients with HFrEF.


Assuntos
Insuficiência Cardíaca , Assistência ao Convalescente , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Alta do Paciente , Volume Sistólico , Resultado do Tratamento , Valsartana , Função Ventricular Esquerda , Remodelação Ventricular
10.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360933

RESUMO

Cisplatin is among the most widely used anticancer drugs used in the treatment of several malignancies, including oral cancer. However, cisplatin treatment often promotes chemical resistance, subsequently causing treatment failure. Several studies have shown that epidermal growth factor receptors (EGFRs) play a variety of roles in cancer progression and overcoming cisplatin resistance. Therefore, this study focused on EGFR inhibitors used in novel targeted therapies as a method to overcome this resistance. We herein aimed to determine whether the combined effects of cisplatin and cetuximab could enhance cisplatin sensitivity by inhibiting the epithelial-to-mesenchymal transition (EMT) process in cisplatin-resistant cells. In vitro analyses of three cisplatin-resistant oral squamous cell carcinoma cells, which included cell proliferation assay, combination index calculation, cell cytotoxicity assay, live/dead cell count assay, Western blot assay, propidium iodide staining assay, scratch assay, and qRT-PCR assay were then conducted. Our results showed that a cisplatin/cetuximab combination treatment inhibited cell proliferation, cell motility, and N-cadherin protein expression but induced E-cadherin and claudin-1 protein expression. Although the combination of cisplatin and cetuximab did not induce apoptosis of cisplatin-resistant cells, it may be useful in treating oral cancer patients with cisplatin resistance given that it controls cell motility and EMT-related proteins.


Assuntos
Cetuximab/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos
11.
Laryngorhinootologie ; 100(S 01): S1, 2021 04.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-34352897

RESUMO

Rare diseases represent a major challenge for affected patients, their relatives, physicians, nursing staff, and therapists. For medical and economic reasons, disease rarity complicates the research and medical care of affected patients. The Hollywood movie, "Lorenzo's Oil", touchingly illustrates the complex problems associated with orphan disease diagnostics, research, and therapy. Directed by George Miller, this film shows the true story of a boy named Lorenzo Michael Murphy Odone, who was diagnosed in 1984 at the age of 6 with the rare neural disease adrenoleukodystrophy (ALD). The movie highlights the manifold problems associated with rare diseases - a large number of which still exist today. However, especially in recent years, orphan diseases have been placed in the focus of public attention.


Assuntos
Adrenoleucodistrofia , Combinação de Medicamentos , Humanos , Masculino
12.
Adv Gerontol ; 34(3): 375-383, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34409816

RESUMO

Continuous improvement of protocols for the treatment of various ailments, in particular, osteochondrosis, is one of the important tasks of providing medical care to elderly patients. Supplementation of treatment with Cytoflavin and biofeed-back therapy seems to be a promising solution, however, it is necessary to develop an algorithm to predict it effectiveness in patients taking into account their initial clinical and psychophysiological status. As a result of the treatment, predictors of the effectiveness of the use of Cytoflavin and biofeed-back therapy have been identified and an algorithm for their administration has been developed.


Assuntos
Inosina Difosfato , Osteocondrose , Idoso , Algoritmos , Combinação de Medicamentos , Mononucleotídeo de Flavina , Humanos , Niacinamida , Succinatos , Resultado do Tratamento
13.
Medicine (Baltimore) ; 100(30): e26809, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397739

RESUMO

ABSTRACT: Sacubitril/valsartan (sac/val) was launched in China in 2018; however, the adoption of sac/val in real-world clinical practice has yet to be described.This study aimed to analyze real-world treatment patterns of sac/val using data from 3 tertiary hospitals in China.A non-interventional, retrospective cohort study of patients with Heart failure (HF) prescribed sac/val from 3 tertiary hospitals in China between January 1, 2018 and June 30, 2020 was conducted. The analysis included sac/val dose titration patterns and persistence during 6 months post-index.A total of 267 patients were included, with a mean age of 63.9 ±â€Š13.1 years. At index, 27% of patients were prescribed sac/val 12/13 mg b.i.d., 63.7% were prescribed 24/26 mg b.i.d., 4.5% were prescribed the target dose of 49/51 mg b.i.d., and 4.8% were not prescribed according to the recommended dose. During the 6 months post-index, 8.3% of patients had only 1 dose titration record. Good therapeutic persistence was observed across sac/val doses, and only 15.7% of patients discontinued sac/val during the 6 months post-index.In China, the majority of patients prescribed sac/val are not initiated on the recommended dose nor up-titrated according to drug instruction. Notably, good persistence with sac/val is observed in the real-world cohort study.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Insuficiência Cardíaca/tratamento farmacológico , Valsartana/uso terapêutico , Idoso , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Kardiologiia ; 61(7): 68-78, 2021 Jul 31.
Artigo em Russo | MEDLINE | ID: mdl-34397344

RESUMO

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.


Assuntos
Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Perindopril
15.
Rev Esp Salud Publica ; 952021 Aug 12.
Artigo em Espanhol | MEDLINE | ID: mdl-34381011

RESUMO

OBJECTIVE: The defined daily dose (DDD) is a measurement unit of drug consumption associated with the Anatomic Therapeutic Chemical (ATC) classification for its use in drug utilization studies. Due to the frequent marketing of pharmaceutical specialties with active ingredients combination, the results of the calculation of DDD product in combination with several active ingredients may vary depending on various possible calculation methods. The aim of this study was to compare different ways to calculate DDD of two groups of drugs that included monodrugs as well as combined products. METHODS: From the prescription billing data during 2019 in Catalonia, the results obtained by three methods when calculating the DDDs of non-insulin hypoglycaemic drugs (nIHG) and drugs used in obstructive respiratory pathology (ORP) were compared. The three methods used were the reference calculation provided by the World Health Organization, the calculation of the considered main ingredient and the individualized calculation of all active ingredients of the combination. These methods were compared using the Wilcoxon test for paired data. RESULTS: The results obtained showed high differences both in the total DDD and in the percentage of participation of each pharmacological subgroup within the studied groups. Differences of 17% were observed in nIHG, and of 118% in ORP drugs. The calculation system that takes into account all the active ingredients of the combinations gives a more approximate idea of the total drug consumption, as well as the relative weight of each subgroup. CONCLUSIONS: The calculation of all the active ingredients included in the specialties with drug combinations seems to be the one that can be most useful in pharmacoepidemiological management scenarios such as those in our environment.


Assuntos
Combinação de Medicamentos , Cálculos da Dosagem de Medicamento , Preparações Farmacêuticas , Humanos , Hipoglicemiantes/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Espanha , Organização Mundial da Saúde
16.
Rev Med Suisse ; 17(747): 1418-1422, 2021 Aug 25.
Artigo em Francês | MEDLINE | ID: mdl-34431635

RESUMO

Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI), is indicated for the treatment of heart failure with reduced ejection fraction. It has demonstrated benefits in terms of cardiovascular morbidity and mortality reduction in this population. Recently, this drug association has also been shown to improve glycemic control and insulin sensitivity in patients with obesity and/or type 2 diabetes. Furthermore, some studies suggest a protective role of this new drug class in diabetic nephropathy. Altogether, these data raise the question about the potential place of ARNI in prevention and treatment of type 2 diabetes, a condition closely associated with heart failure.


Assuntos
Diabetes Mellitus Tipo 2 , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Humanos , Neprilisina , Valsartana
17.
Clin Drug Investig ; 41(9): 785-794, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333742

RESUMO

BACKGROUND AND OBJECTIVE: In asthma, symptom control is a primary goal that is not consistently met with available treatment options. The first commercially available fixed-dose combination in a single inhaler of a long-acting beta-agonist (indacaterol, IND), an inhaled corticosteroid (mometasone furoate, MF) and a long-acting muscarinic antagonist (glycopyrronium, GLY) has shown promising clinical results in phase III trials. The aim of the present study is to evaluate the cost-utility of IND/GLY/MF fixed-dose combination relative to a combination of salmeterol/fluticasone and tiotropium or salmeterol/fluticasone or IND/MF in adult patients with asthma, from the Italian Health Service (NHS) perspective. METHODS: A two-state and 4-week cycle Markov model was used to estimate lifetime clinical outcomes and costs. Patients entered the model in stable disease and could experience a non-fatal exacerbation event. The exacerbation rate is dependent upon the therapy a patient is receiving, as per the IND/GLY/MF clinical trials. The impact of each type of exacerbation is accounted by applying a utility decrement, obtained from the literature, and a treatment cost. Utility values were obtained from the EQ-5D questionnaires in the IND/GLY/MF clinical trials. Lifetime costs considered in the analysis were drugs and exacerbation management. Probabilistic sensitivity analyses were carried out, with the aim of evaluating the impact of uncertainty on input parameters. RESULTS: IND/GLY/MF is associated with a higher quality of life [+ 0.25 quality-adjusted life-year (QALY)] than salmeterol/fluticasone plus tiotropium, with an incremental cost of -€3213.90. The incremental cost-utility ratio indicates dominance. At a threshold of €5000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.21 QALY) than salmeterol/fluticasone, with an incremental cost of €2547.76. Incremental cost-utility ratio results in €11,897 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.34 QALY) than IND/MF, with an incremental cost of €4745.91. Incremental cost-utility ratio results in €14,088 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. CONCLUSION: The results indicate that IND/GLY/MF is cost effective against the considered comparators in a cohort representative of adult patients with asthma in Italy.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Acetatos/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Análise Custo-Benefício , Combinação de Medicamentos , Glicopirrolato , Humanos , Indanos , Furoato de Mometasona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Quinolonas , Resultado do Tratamento
18.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361789

RESUMO

Isobavachalcone (IBC) is an active substance from the medicinal plant Psoralea corylifolia. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Chalconas/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Psoralea/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ligação Competitiva , Linhagem Celular Tumoral , Chalconas/química , Chalconas/isolamento & purificação , Cães , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Células HT29 , Humanos , Concentração Inibidora 50 , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Células Madin Darby de Rim Canino , Membranas Artificiais , Modelos Moleculares , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Extratos Vegetais/química , Plantas Medicinais , Ligação Proteica , Transgenes , Verapamil/farmacologia
19.
Nutrients ; 13(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34444708

RESUMO

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes -9 or -10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.


Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Óleos de Peixe/administração & dosagem , Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento/epidemiologia , Azeite de Oliva/administração & dosagem , Fosfolipídeos/administração & dosagem , Sorbitol/administração & dosagem , Óleo de Soja/administração & dosagem , Triglicerídeos/administração & dosagem , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/prevenção & controle , Estudos Transversais , Combinação de Medicamentos , Epilepsia/epidemiologia , Epilepsia/prevenção & controle , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/prevenção & controle , Estudos Retrospectivos
20.
Adv Ther ; 38(9): 4815-4835, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34347255

RESUMO

INTRODUCTION: Smoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD. METHODS: The 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS. Current and former smoker subgroups were defined by smoking status at screening. RESULTS: The analysis included 1203 (50%) current smokers and 1221 (50%) former smokers. Both subgroups demonstrated greater improvements from baseline in trough FEV1 at week 24 (primary endpoint) with umeclidinium/vilanterol versus umeclidinium (least squares [LS] mean difference, mL [95% CI]; current: 84 [50, 117]; former: 49 [18, 80]) and salmeterol (current: 165 [132, 198]; former: 117 [86, 148]) and larger reductions in rescue medication inhalations/day over 24 weeks versus umeclidinium (LS mean difference [95% CI]; current: - 0.42 [- 0.63, - 0.20]; former: - 0.25 - 0.44, - 0.05]) and salmeterol (current: - 0.28 [- 0.49, - 0.06]; former: - 0.29 [- 0.49, - 0.09]). Umeclidinium/vilanterol increased the odds (odds ratio [95% CI]) of clinically significant improvement at week 24 in Transition Dyspnea Index versus umeclidinium (current: 1.54 [1.16, 2.06]; former: 1.32 [0.99, 1.75]) and salmeterol (current: 1.37 (1.03, 1.82]; former: 1.60 [1.20, 2.13]) and Evaluating Respiratory Symptoms-COPD versus umeclidinium (current: 1.54 [1.13, 2.09]; former: 1.50 [1.11, 2.04]) and salmeterol (current: 1.53 [1.13, 2.08]; former: 1.53 [1.12, 2.08]). All treatments were well tolerated in both subgroups. CONCLUSIONS: In current and former smokers, umeclidinium/vilanterol provided greater improvements in lung function and symptoms versus umeclidinium and salmeterol, supporting consideration of dual-bronchodilator therapy in symptomatic patients with COPD regardless of their smoking status.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Fumantes , Administração por Inalação , Álcoois Benzílicos , Broncodilatadores/uso terapêutico , Clorobenzenos/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/uso terapêutico , Resultado do Tratamento
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