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1.
Viruses ; 13(7)2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34372560

RESUMO

The combination of the two nucleoside reverse transcriptase inhibitors (NRTI) tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is used in most highly active antiretroviral therapies for treatment of HIV-1 infection, as well as in pre-exposure prophylaxis against HIV acquisition. Administered as prodrugs, these drugs are taken up by HIV-infected target cells, undergo intracellular phosphorylation and compete with natural deoxynucleoside triphosphates (dNTP) for incorporation into nascent viral DNA during reverse transcription. Once incorporated, they halt reverse transcription. In vitro studies have proposed that TDF and FTC act synergistically within an HIV-infected cell. However, it is unclear whether, and which, direct drug-drug interactions mediate the apparent synergy. The goal of this work was to refine a mechanistic model for the molecular mechanism of action (MMOA) of nucleoside analogues in order to analyse whether putative direct interactions may account for the in vitro observed synergistic effects. Our analysis suggests that depletion of dNTP pools can explain apparent synergy between TDF and FTC in HIV-infected cells at clinically relevant concentrations. Dead-end complex (DEC) formation does not seem to significantly contribute to the synergistic effect. However, in the presence of non-nucleoside reverse transcriptase inhibitors (NNRTIs), its role might be more relevant, as previously reported in experimental in vitro studies.


Assuntos
Emtricitabina/uso terapêutico , HIV-1/efeitos dos fármacos , Tenofovir/uso terapêutico , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade/métodos , Desoxicitidina/análogos & derivados , Quimioterapia Combinada/métodos , Infecções por HIV/tratamento farmacológico , Transcriptase Reversa do HIV/genética , HIV-1/patogenicidade , Humanos , Modelos Teóricos , Profilaxia Pré-Exposição/métodos , Transcrição Reversa/efeitos dos fármacos , Tenofovir/metabolismo
2.
Medicine (Baltimore) ; 100(30): e26641, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397691

RESUMO

BACKGROUND: This review aims to evaluate the supportive effects of frequently used traditional Chinese medicine (TCM) for the treatment of coronavirus disease 2019 (COVID-19). METHODS: Five databases were searched through July 7, 2020. Randomized controlled trials investigating the efficacy of TCM for use in the treatment of COVID-19 were included. Newcastle-Ottawa Scale (NOS) and modified Jadad score were used for the evaluation of the methodological quality of the included studies. Weighted mean difference, odds ratio (OR), and 95% confidence interval (95% CI) were calculated for pooling out results. Data were extracted for conducting a meta-analysis using STATA version 12.0. RESULTS: Eight studies with a total of 750 patients were included in this meta-analysis. All included trial groups involved treatment with TCM and Western medicine, while the control groups were treated only with Western medicine. The intervention therapy significantly improved the overall effective rate (n = 346, OR = 2.5, 95% CIs = 1.46-4.29), fever symptom disappearance rate (n = 436; OR = 3.6; 95% CIs = 2.13-6.08), fatigue symptom disappearance rate (n = 436; OR = 3.04; 95% CIs = 1.76-5.26), cough symptom disappearance rate (n = 436; OR = 2.91; 95% CIs = 1.36-6.19), and sputum production reduction (n = 436; OR = 5.51; 95% CIs = 1.94-15.64). Based on the Newcastle-Ottawa Scale assessment, 6 studies received a score of 4, and 1 study achieved a score of 5. One study was assessed using the modified Jadad score, achieving a score of 6. CONCLUSIONS: The integration of TCM with Western medicine has significantly improved the treatment for COVID-19 patients compared to Western medicine treatment alone. Combined therapy using TCM and Western medicine revealed the potential adjunctive role of TCM in treating COVID-19. However, high-quality clinical studies are still required to further evaluate the efficacy and safety of TCM in the treatment of COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Quimioterapia Combinada/métodos , Humanos , Medicina Tradicional Chinesa/métodos , Resultado do Tratamento
3.
Medicine (Baltimore) ; 100(31): e26787, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397829

RESUMO

BACKGROUND: Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir. METHODS: In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies. RESULTS: We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment. CONCLUSION: Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.


Assuntos
Sulfato de Atazanavir/efeitos adversos , Síndrome do QT Longo/etiologia , Lopinavir/efeitos adversos , Ritonavir/efeitos adversos , Saquinavir/efeitos adversos , Adulto , Sulfato de Atazanavir/uso terapêutico , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Eletrocardiografia/métodos , Humanos , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Saquinavir/uso terapêutico
4.
Front Immunol ; 12: 695972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341659

RESUMO

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.


Assuntos
COVID-19/imunologia , Granulócitos/imunologia , Células Supressoras Mieloides/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Arginase/antagonistas & inibidores , Arginase/metabolismo , Arginina/administração & dosagem , Arginina/sangue , Arginina/metabolismo , Infecções Assintomáticas , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Estudos de Casos e Controles , Quimioterapia Combinada/métodos , Inibidores Enzimáticos/administração & dosagem , Feminino , Granulócitos/metabolismo , Voluntários Saudáveis , Humanos , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/imunologia , Linfócitos T/imunologia
5.
Crit Rev Ther Drug Carrier Syst ; 38(3): 75-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34348019

RESUMO

The outbreak of novel coronavirus (nCoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in December 2019 in Wuhan, China, has posed an international public health emergency worldwide and forced people to be confined in their homes. This virus is of high-risk category and is declared a pandemic by the World Health Organization (WHO). The worldwide researchers and various health professionals are working together to determine the best way to stop its spread or halt this virus's spread and circumvent this pandemic condition threatening millions of human lives. The absence of definitive treatment is possible to explore to reduce virus infection and enhance patient recovery. Along with off-label medicines, plasma therapy, vaccines, the researchers exploit the various plants/herbs and their constituents to effectively treat nCoV infection. The present study aimed to present brief and most informative salient features of the numerous facts regarding the SARS-CoV-2, including the structure, genomic sequence, recent mutation, targeting possibility, and various hurdles in research progress, and off-labeled drugs, convalescent plasma therapy, vaccine and plants/herbs for the treatment of coronavirus disease-2019 (COVID-19). Results showed that off-labeled drugs such as hydroxychloroquine, dexamethasone, tocilizumab, antiviral drug (remdesivir, favipiravir), etc., give positive results and approved for use or approved for restricted use in some countries like India. Future research should focus on these possibilities that may allow the development of an effective treatment for COVID-19.


Assuntos
Antivirais/farmacologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/tratamento farmacológico , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/uso terapêutico , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Ensaios Clínicos como Assunto , Quimioterapia Combinada/métodos , Humanos , Terapia de Alvo Molecular/métodos , Mutação , Uso Off-Label , Pandemias/prevenção & controle , Extratos Vegetais/uso terapêutico , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Resultado do Tratamento , Proteínas Estruturais Virais/antagonistas & inibidores , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/metabolismo
6.
J Am Coll Cardiol ; 78(1): 27-38, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34210411

RESUMO

BACKGROUND: The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. OBJECTIVES: The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG. METHODS: This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality. RESULTS: In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without. CONCLUSIONS: In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Ponte de Artéria Coronária , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Período Pós-Operatório , Resultado do Tratamento
7.
Lancet Child Adolesc Health ; 5(9): 642-651, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34302760

RESUMO

BACKGROUND: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. METHODS: In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per µL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. INTERPRETATION: In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. FUNDING: Gilead Sciences.


Assuntos
Alanina , Antirretrovirais , Monitoramento de Medicamentos/métodos , Emtricitabina , Infecções por HIV , Tenofovir/análogos & derivados , Adolescente , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/farmacocinética , Amidas/administração & dosagem , Amidas/efeitos adversos , Amidas/farmacocinética , Antirretrovirais/administração & dosagem , Antirretrovirais/efeitos adversos , Antirretrovirais/farmacocinética , Contagem de Linfócito CD4/métodos , Criança , Cálculos da Dosagem de Medicamento , Quimioterapia Combinada/métodos , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Emtricitabina/farmacocinética , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Humanos , Masculino , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Piridonas/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/farmacocinética , Resultado do Tratamento , Carga Viral/métodos
8.
Cancer Sci ; 112(9): 3856-3870, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34288281

RESUMO

Patients with BRAF-mutated colorectal cancer (CRC) have a poor prognosis despite recent therapeutic advances such as combination therapy with BRAF, MEK, and epidermal growth factor receptor (EGFR) inhibitors. To identify microRNAs (miRNAs) that can improve the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), we screened 240 miRNAs in BRAF-mutated CRC cells and identified five candidate miRNAs. Overexpression of miR-193a-3p, one of the five screened miRNAs, in CRC cells inhibited cell proliferation by inducing apoptosis. Reverse-phase protein array analysis revealed that proteins with altered phosphorylation induced by miR-193a-3p were involved in several oncogenic pathways including MAPK-related pathways. Furthermore, overexpression of miR-193a-3p in BRAF-mutated cells enhanced the efficacy of DAB and TRA through inhibiting reactivation of MAPK signaling and inducing inhibition of Mcl1. Inhibition of Mcl1 by siRNA or by Mcl1 inhibitor increased the antiproliferative effect of combination therapy with DAB, TRA, and anti-EGFR antibody cetuximab. Collectively, our study demonstrated the possibility that miR-193a-3p acts as a tumor suppressor through regulating multiple proteins involved in oncogenesis and affects cellular sensitivity to MAPK-related pathway inhibitors such as BRAF inhibitors, MEK inhibitors, and/or anti-EGFR antibodies. Addition of miR-193a-3p and/or modulation of proteins involved in the miR-193a-3p-mediated pathway, such as Mcl1, to EGFR/BRAF/MEK inhibition may be a potential therapeutic strategy against BRAF-mutated CRC.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Genes Supressores de Tumor , Imidazóis/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Mutação , Oximas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/farmacologia , Pirimidinonas/farmacologia , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Cetuximab/farmacologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Quimioterapia Combinada/métodos , Receptores ErbB/antagonistas & inibidores , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transfecção
9.
Nat Commun ; 12(1): 3247, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059688

RESUMO

The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Fraturas do Fêmur/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteínas Wnt/agonistas , Idoso , Envelhecimento/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/fisiopatologia , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Feminino , Fraturas do Fêmur/patologia , Fêmur/efeitos dos fármacos , Fêmur/lesões , Fêmur/patologia , Humanos , Camundongos , Osteoporose Pós-Menopausa/fisiopatologia , Via de Sinalização Wnt/efeitos dos fármacos , Adulto Jovem
10.
Cochrane Database Syst Rev ; 6: CD008084, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34190331

RESUMO

BACKGROUND: This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning. SEARCH METHODS: The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI ); Wanfang Data (); and VIP () on 12 November 2020. We examined the reference lists of included studies and review papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections. DATA COLLECTION AND ANALYSIS: We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all-cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta-analysis, using a fixed-effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment. MAIN RESULTS: We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low-certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I2 = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low-certainty evidence); however, analysis of long-term results amongst participants whose injuries arose from self-poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low-certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants. AUTHORS' CONCLUSIONS: Low-certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT-compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long-term follow-up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Herbicidas/envenenamento , Imunossupressores/uso terapêutico , Paraquat/envenenamento , Fibrose Pulmonar/tratamento farmacológico , Adulto , Viés , Causas de Morte , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Envenenamento/tratamento farmacológico , Envenenamento/mortalidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
11.
Medicine (Baltimore) ; 100(23): e25313, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114978

RESUMO

ABSTRACT: Changes in tryptophan metabolism affect human physiology including the immune system, mood, and sleep and are associated with human immunodeficiency virus (HIV) pathogenesis. This study investigates whether the treatment of HIV-infected individuals with the neurokinin-1 receptor antagonist, aprepitant, alters tryptophan metabolism.This study utilized archival samples from 3 phase 1B clinical trials "Anti-HIV Neuroimmunomodulatory Therapy with Neurokinin-1 Antagonist Aprepitant"-2 double-blinded, placebo-controlled, and 1 open-label study. We tested samples from a total of 57 individuals: 26 combination antiretroviral therapy (cART) naïve individuals receiving aprepitant, 19 cART naïve individuals receiving placebo, and 12 individuals on a ritonavir-containing cART regimen receiving aprepitant. We evaluated the effect of aprepitant on tryptophan metabolism by measuring levels of kynurenine and tryptophan in archival plasma samples and calculating the kynurenine to tryptophan ratio.Aprepitant treatment affected tryptophan metabolism in both cART treated and cART naïve individuals with more profound effects in patients receiving cART. While aprepitant treatment affected tryptophan metabolism in all HIV-infected patients, it only significantly decreased kynurenine to tryptophan ratio in cART treated individuals. Aprepitant treatment offers an opportunity to target inflammation and mood disorders frequently co-existing in chronic HIV infection.


Assuntos
Aprepitanto , Infecções por HIV , Transtornos do Humor , Neuroimunomodulação/efeitos dos fármacos , Ritonavir , Triptofano/metabolismo , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Aprepitanto/administração & dosagem , Aprepitanto/efeitos adversos , Contagem de Linfócito CD4/métodos , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Cinurenina/análise , Masculino , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/etiologia , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Resultado do Tratamento
12.
Cochrane Database Syst Rev ; 6: CD008907, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34155624

RESUMO

BACKGROUND: This is an update of a review first published in 2011, and last updated in 2017. Most people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the following databases on 10 September 2020: Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid). CRS Web includes randomized or quasi-randomized, controlled trials from Specialized Registers of Cochrane Review Groups including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov and the WHO ICTRP. There were no language restrictions. We reviewed the reference lists of retrieved studies and contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo-controlled double-blind add-on trials of ESL in people with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. MAIN RESULTS: We included seven trials (2185 participants, aged 2 to 77 years), which were at low or unclear risk of bias apart from a high risk of attrition bias; all studies were funded by the pharmaceutical company, BIAL. The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.57 (95% confidence interval (CI) 1.34 to 1.83). For adults, the RR was 1.71 (95% CI 1.42 to 2.05; 5 studies, 1799 participants; moderate-certainty evidence); for children aged six to 18 years, the RR was 1.35 (95% CI 0.98 to 1.87; 2 studies, 322 participants; moderate-certainty evidence). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was associated with seizure freedom (RR 3.16, 95% CI 1.73 to 5.78; 6 studies, 1922 participants; moderate-certainty evidence). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.72, 95% CI 1.66 to 4.46; 7 studies, 2185 participants; moderate-certainty evidence), but not for any reason (RR 1.25, 95% CI 0.93 to 1.70; 7 studies, 2185 participants; moderate-certainty evidence). The following adverse effects were associated with ESL: dizziness (RR 2.77, 99% CI 1.85 to 4.15); nausea (RR 2.55, 99% CI 1.39 to 4.67); somnolence (RR 1.75, 99% CI 1.18 to 2.61); diplopia (RR 4.07, 99% CI 1.86 to 8.89); and vomiting (RR 2.37, 99% CI 1.19 to 4.74). Overall, the certainty of the evidence was moderate due to a high discontinuation rate in studies of adults. AUTHORS' CONCLUSIONS: ESL reduces seizure frequency when used as an add-on treatment for adults with drug-resistant focal epilepsy. The trials included in this review were of short-term duration. In addition, this update found that ESL may reduce seizure frequency in children from 6 to 18 years of age; however the results are inconclusive.


Assuntos
Anticonvulsivantes/uso terapêutico , Dibenzazepinas/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Anticonvulsivantes/efeitos adversos , Viés , Criança , Dibenzazepinas/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Suspensão de Tratamento/estatística & dados numéricos , Adulto Jovem
13.
Cochrane Database Syst Rev ; 6: CD002007, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34159577

RESUMO

BACKGROUND: The choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in CF requires further evaluation. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of single compared to combination intravenous anti-pseudomonal antibiotic therapy for treating people with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search of the Group's Trials Register: 07 October 2020. We also searched online trials registries on 16 November 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a single intravenous anti-pseudomonal antibiotic with a combination of that antibiotic plus a second anti-pseudomonal antibiotic in people with CF. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We assessed the certainty of the data using GRADE. MAIN RESULTS: We identified 59 trials, of which we included eight trials (356 participants) comparing a single anti-pseudomonal agent to a combination of the same antibiotic and one other. There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination.  There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single-centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor and the certainty of the evidence ranged from low to moderate. The review did not find any differences between monotherapy and combination therapy in either the short term or in the long term for the outcomes of different lung function measures, bacteriological outcome measures, need for additional treatment, adverse effects, quality of life or symptom scores. AUTHORS' CONCLUSIONS: The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well-designed in terms of adequate randomisation allocation, blinding, power and long-term follow-up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Fibrose Cística/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Infecções Respiratórias/tratamento farmacológico , Adulto , Aminoglicosídeos/administração & dosagem , Cefalosporinas/administração & dosagem , Criança , Quimioterapia Combinada/métodos , Humanos , Injeções Intravenosas , Ensaios Clínicos Controlados Aleatórios como Assunto , beta-Lactamas/administração & dosagem
14.
Medicine (Baltimore) ; 100(26): e26438, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190167

RESUMO

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, are effective but still have limited efficacy. Therefore, combination therapy is preferable to using a single drug alone in high-risk patients. We performed a comparative study on the antiemetic effect of palonosetron, a 5-HT3 receptor antagonist, monotherapy vs palonosetron-midazolam combination therapy for the prevention of PONV. METHODS: A total of 104 female patients scheduled for breast cancer surgery were enrolled. They were randomly divided into 2 groups, a palonosetron monotherapy group (group P) and palonosetron-midazolam combination therapy group (group PM). Both groups received 0.075 mg palonosetron intravenously after induction of anesthesia. Patient-controlled analgesia (PCA) was applied according to the allocated group. Intravenous (IV)-PCA in group P consisted of fentanyl 20 µg/kg plus normal saline (total volume: 100 ml); IV-PCA in group PM consisted of fentanyl 20 µg/kg plus midazolam 4 mg plus normal saline (total volume: 100 ml). Efficacy parameters were collected during 0 to 1, 1 to 6, 6 to 24, and 24 to 48 hours postoperative time intervals. These measures included complete response (defined as no PONV and no rescue anti-emetic use) rate, incidence of PONV, sedation score, rescue antiemetic use, rescue analgesic use, and numerical rating scale (NRS) for pain. The complete response rate during the 0 to 24 hours interval was analyzed as the primary outcome. RESULTS: Although the complete response rate between 0 and 24 hours was higher in group PM (42.3% and 48.1% in group P and PM, respectively), there was no statistically significant difference (P = .55). The complete response rates in other time intervals were not different between the 2 groups as well. The sedation score and NRS score also showed no differences between the 2 groups. CONCLUSIONS: The combination therapy of palonosetron with midazolam did not lead to a greater reduction in the incidence of PONV than monotherapy in patients undergoing breast surgery and receiving IV-PCA containing fentanyl.


Assuntos
Analgesia Controlada pelo Paciente/efeitos adversos , Neoplasias da Mama/cirurgia , Fentanila , Midazolam/administração & dosagem , Palonossetrom/administração & dosagem , Náusea e Vômito Pós-Operatórios , Anestésicos Intravenosos/administração & dosagem , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Mastectomia/efeitos adversos , Mastectomia/métodos , Midazolam/efeitos adversos , Pessoa de Meia-Idade , Palonossetrom/efeitos adversos , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Resultado do Tratamento
15.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073930

RESUMO

Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.


Assuntos
Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada/métodos , Epilepsia/tratamento farmacológico , Lacosamida/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/efeitos adversos , Modelos Animais de Doenças , Interações Medicamentosas , Sinergismo Farmacológico , Eletrochoque , Lacosamida/efeitos adversos , Lamotrigina/efeitos adversos , Lamotrigina/uso terapêutico , Masculino , Camundongos , Oxcarbazepina/efeitos adversos , Oxcarbazepina/uso terapêutico , Pregabalina/efeitos adversos , Pregabalina/uso terapêutico , Topiramato/efeitos adversos , Topiramato/uso terapêutico
16.
Medicine (Baltimore) ; 100(25): e26264, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160390

RESUMO

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer. METHODS: The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The "Risk of Bias Assessment" tool and the "Jadad Scale" provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software. RESULTS: In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22-1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09-1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results. CONCLUSION: Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants.


Assuntos
Aborto Habitual/prevenção & controle , Anticoagulantes/administração & dosagem , Síndrome Antifosfolipídica/tratamento farmacológico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Trombose/tratamento farmacológico , Aborto Habitual/sangue , Aborto Habitual/imunologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Aspirina/administração & dosagem , Biomarcadores/sangue , Coeficiente de Natalidade , Quimioterapia Combinada/métodos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Nascido Vivo , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/imunologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose/sangue , Trombose/complicações , Trombose/imunologia , Resultado do Tratamento
17.
Medicine (Baltimore) ; 100(25): e26373, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160411

RESUMO

RATIONALE: Hepatocellular carcinoma (HCC) is the most common liver cancer. The efficacy of the present treatment is disappointing, and the prognosis is poor. Donafenib, a novel multikinase inhibitor, is a new deuterated derivative of sorafenib. It can improve overall survival in patients with advanced HCC, with a favorable safety and tolerability profile over sorafenib. PATIENT CONCERNS: Here, we report the case of a 51-year-old male patient who presented with experienced epigastric discomfort for the prior several days. He had a history of untreated chronic hepatitis B virus infection for >29 years and no other underlying diseases. Based on further investigations, he was diagnosed with advanced HCC and refused surgery. DIAGNOSIS: Based on the patient's performance status, tumor status assessed by computed tomography, liver function, and percutaneous liver biopsy, he was diagnosed with advanced HCC Barcelona Clinic Liver Cancer Stage C. INTERVENTIONS: The patient was administered a 200-mg oral dose of donafenib twice-daily. OUTCOMES: The patient was followed-up from the time of diagnosis. He received donafenib for 31 months, and the progression-free survival time was 31 months (from May 2017 to December 2019); the overall survival time was not reached. The patient reported little abdominal distension with no other obvious discomfort while taking the medication. LESSON: Donafenib showed good efficacy for the treatment of advanced HCC, with mild side effects. Deuterium-containing drugs seem to be a promising avenue for medical innovation.


Assuntos
Carcinoma Hepatocelular/terapia , Guanina/análogos & derivados , Hepatite B Crônica/terapia , Neoplasias Hepáticas/terapia , Piridinas/uso terapêutico , Biópsia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Quimioterapia Combinada/métodos , Guanina/uso terapêutico , Hepatectomia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Medicine (Baltimore) ; 100(25): e26374, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160412

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease of the spine, which mainly invades the sacroiliac joint, spine, and large joints near the trunk, leading to fibrous and skeletal ankylosis and deformity, and can cause damage to the eyes, lung, cardiovascular, kidney and other organs. Chinese herbal formulas (CHF) is an important interventions of Traditional Chinese Medicine (TCM), and CHFs combined with western medicine are widely used in clinical practice to treat AS. METHODS: Eight databases will be systematically retrieved from their inceptions to March 2021. Only randomized controlled trials (RCTs) of CHFs combined with western medicine for AS treatment will meet the inclusion criteria. The primary outcomes we focus on include clinical effectiveness rate, TCM syndrome score, TCM symptom score, Bath ankylosing spondylitis disease activity index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, nocturnal spinal pain, adverse reactions, erythrocyte sedimentation rate (ESR), and C protein response (CRP). The research screening, data extraction, and risk of bias assessment will be performed independently by 2 researchers, and divergence will be solved by a third researcher. Revman 5.3 software will be used for meta-analysis. The confidence of evidence will be graded using grading of recommendations assessment, development, and evaluation (GRADE) algorithm and methodological quality will be assessed adopting risk of bias in systematic reviews (ROBIS). RESULTS: This systematic review (SR) will provide evidence-based medical evidence for AS therapy by CHF combined with western medicine and we will submit the findings of this SR for peer-review publication. CONCLUSIONS: This SR will provide latest and updated summary proof for assessing the effectiveness and safety of CHF combined with western medicine for AS. REGISTRATION NUMBER: INPLASY 202150089.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antirreumáticos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Imunossupressores/administração & dosagem , Espondilite Anquilosante/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Antirreumáticos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/imunologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
19.
Medicine (Baltimore) ; 100(25): e26387, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160417

RESUMO

RATIONALE: Group B Streptococcus (GBS) remains a principal pathogen causing neonatal sepsis and meningitis, particularly in premature infants with relatively insufficient immunity. Recurrence may occur uncommonly, largely associated with subclinical mucosal persistence or repetitive exposure to exogenous sources. White matter injury (WMI) including cystic periventricular leukomalacia (PVL) has been associated with intrauterine infection/inflammation, and neonatal infection as a more significant predictor including postnatal sepsis and recurrent infection, even without microbial neuroinvasion. Furthermore, clinical and experimental evidence of WMI by some bacteria other than GBS without central nervous system invasion has been reported. However, there is little evidence of WMI associated with neonatal GBS sepsis in the absence of meningitis in the literature. PATIENT CONCERNS: A newborn at 30+4 weeks' gestation with low birthweight presented with 2 episodes (with a 13-day interval with no antibiotic therapy) of neonatal sepsis culture-proven for GBS with early-onset presentation after clinical chorioamnionitis via vertical GBS transmission and the associated conditions including prematurity-related neonatal immunodeficiency and persistent mucosal GBS carriage after the first antibiotic treatment. The perinatal GBS infection was complicated by progressive WMI presenting with ventriculomegaly and cystic PVL without a definite evidence of meningitis, intraventricular hemorrhage, and documented cerebral hypoxia or hypoperfusion conditions including septic shock. DIAGNOSES: Recurrent group B streptococcal sepsis and cystic PVL with ventriculomegaly. INTERVENTIONS: Two episodes of GBS sepsis were treated with 15-day parenteral antibiotic therapy, respectively. OUTCOMES: Resolution of the recurrent GBS sepsis without further relapses, however, complicated by WMI and subsequent about 6 months delay in motor development at 12 months' corrected age. LESSONS: This case suggests WMI associated with GBS bacteremia without central nervous system entry by viable GBS and also shows that in premature infants, intrauterine GBS infection with no interventions may lead to extensive and persistent GBS colonization, early-onset and recurrent GBS disease, and WMI. Postnatal as well as intrauterine infection/inflammation controls with maternal prophylaxis may be pivotal for prevention and limiting the magnitude of neurologic injury.


Assuntos
Leucomalácia Periventricular/microbiologia , Sepse Neonatal/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus agalactiae/isolamento & purificação , Administração Intravenosa , Antibacterianos/administração & dosagem , Corioamnionite/diagnóstico , Corioamnionite/microbiologia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/microbiologia , Quimioterapia Combinada/métodos , Feminino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/microbiologia , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Transmissão Vertical de Doenças Infecciosas , Leucomalácia Periventricular/diagnóstico , Leucomalácia Periventricular/patologia , Imageamento por Ressonância Magnética , Masculino , Idade Materna , Sepse Neonatal/diagnóstico , Sepse Neonatal/terapia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Recidiva , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/transmissão , Substância Branca/diagnóstico por imagem , Substância Branca/microbiologia , Substância Branca/patologia , Adulto Jovem
20.
Medicine (Baltimore) ; 100(25): e26416, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160429

RESUMO

BACKGROUND: Cough variant asthma (CVA) is classified as a distinct form of asthma. As the primary or only symptom, cough is the leading cause for the most prevalent chronic cough among kids. The American College of Clinical Pharmacy, British Thoracic Society, and Chinese guidelines established for diagnosing and treating chronic cough in kids recommend inhaled corticosteroids, combined with leukotriene receptor antagonists when necessary. METHODS: We will conduct a comprehensive search in major databases using keywords to find studies related to the analysis of montelukast sodium and budesonide for treating CVA in kids. Two reviewers will independently assess the quality of the selected research articles and perform data extraction. Next, we will use the RevMan software (version: 5.3) to conduct the statistical analysis of the present study. RESULTS: This study will assess the efficacy and safeness of using montelukast sodium and budesonide to treat kids with CVA by pooling the results of individual studies. CONCLUSION: Our findings will provide vigorous evidence to judge whether montelukast sodium and budesonide therapy is an efficient form of therapy for CVA patients. ETHICS AND DISSEMINATION: Ethics approval is not needed for the present meta-analysis. OSF REGISTRATION NUMBER: May 17, 2021.osf.io/cuvjz (https://osf.io/cuvjz/).


Assuntos
Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Glucocorticoides/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Administração por Inalação , Asma/diagnóstico , Asma/imunologia , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Doença Crônica/tratamento farmacológico , Tosse/diagnóstico , Tosse/imunologia , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Glucocorticoides/efeitos adversos , Humanos , Antagonistas de Leucotrienos/efeitos adversos , Metanálise como Assunto , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto , Resultado do Tratamento
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