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1.
Artigo em Inglês | MEDLINE | ID: mdl-32374907

RESUMO

The present study compared performances of the 3 major methods used for assessing platelet reactivity (PR)-VerifyNow, light-transmission aggregometry (LTA), and thromboelastography (TEG)-to predict ischaemic events in patients receiving clopidogrel. PubMed, EmBase and the Cochrane library were searched from their inception to April 2019 for prospective studies that examined PR using VerifyNow, LTA or TEG and the incidence of ischaemic events. The investigated diagnostic indices including sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio, and area under the receiver operating characteristic curves (AUC) of VerifyNow, LTA, and TEG, respectively. A total of 26 prospective studies involving 22,185 subjects were included in the analysis. The pooled AUC was 0.71 (95% CI: 0.67-0.75) for VerifyNow, 0.60 (95% CI: 0.55-0.64) for LTA, and 0.81 (95% CI: 0.77-0.84) for TEG. Results of indirect comparisons indicated the AUC of VerifyNow was higher than that of LTA (1.18, 95% CI: 1.08-1.30) and lower than that of TEG (0.88, 95% CI: 0.82-0.94). TEG outperformed the other 2 methods for assessing PR in all predictive measures, including sensitivity, specificity, PLR, and NLR. Despite a lack of studies that directly compared the 3 methods, our findings suggest that TEG should be recommended.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32125144

RESUMO

Lightweight, broad-band, and highly efficient microwave-absorbing materials (MAMs) with tunable electromagnetic properties are in high demand. However, the absorption properties are limited by the simple loss mechanism in commonly used absorbing materials. Here, we tested the microwave-absorbing properties of Fe-NiS2/NiS/poly(vinylidene fluoride) (PVDF) in the frequency range of 2-18 GHz. For the 2.5% Fe-NiS2/NiS/PVDF with the filling content of 20 wt %, the maximum reflection loss can reach -61.72 dB at 14.88 GHz, and the bandwidth can reach 3.8 GHz with the reflection loss value below -10 dB. Loss mechanisms of different composites were analyzed on the basis of their magnetic and dielectric properties using both experimental and computational methods. The results indicate that strong microwave absorption property is achieved through a balancing of dielectric loss and magnetic loss. These findings present a new strategy for the future design of MAMs.

3.
Int J Clin Pharm ; 42(2): 366-377, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32078109

RESUMO

Background The clinical pharmacist has been an important partner in clinical treatment team. In China, there is no systematic review to evaluate the effectiveness of clinical pharmacy services on patients' outcomes such as hospitalization days, readmission rate and mortality. Aim of the review To investigate the impact of clinical pharmacist services on patients' length of hospitalization, readmission and mortality in China. Methods A literature search was performed in PubMed, EMBASE, Cochrane Library, clinicaltrials.gov, and a Chinese database (up to January 2019). Randomized control trials or pre- to post-intervention comparison studies were included to investigate the impact of clinical pharmacist-led interventions on the length of stay, readmission rate and mortality of inpatients. Basic information, intervention and therapeutic area were extracted. Results After screening all articles from the mentioned databases, 14 studies were included for meta- analysis and subgroup analysis. Most studies focused on cardiology and respiratory diseases. Results show that clinical pharmacist services can reduce the length of stay of inpatients (MD: - 3.00, 95% CI - 4.72 to - 1.29, P < 0.01) and the readmission rate (RR 0.44, 95% CI 0.35-0.56, P < 0.01) as well as the mortality of patients during hospitalization (RR 0.57, 95% CI 0.35-0.92, P = 0.02). Conclusions Clinical pharmacist-led interventions could significantly reduce Chinese patients' length of hospitalization and readmission rate. More studies are needed to confirm the relationship between the clinical pharmacist-led interventions and patients' mortality.

4.
J Clin Pharm Ther ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107837

RESUMO

OBJECTIVE: In patients with asthma and chronic obstructive pulmonary disease (COPD), disease control is still suboptimal-incorrect inhalation technique and medication non-adherence are two important reasons for this outcome. Pharmacists' interventions have been shown to have a positive effect on the clinical outcomes of asthma and COPD. Quantitative assessment of the efficacy of pharmacist-led interventions, mainly on inhalation techniques and medication adherence, is needed. Evidence for different interventions is not totally conclusive, and no results of theory-based adherence promotion interventions for asthma and COPD have been published. The objective of our study is to evaluate the effect of pharmacist-led interventions on asthma and COPD management, focusing mainly on inhalation technique and medication adherence, and whether the content of interventions (categorized based on Information-Motivation-Behavioural skills (IMB) model) affects the effectiveness and whether the IMB model is worthy of clinical promotion and application in adults with asthma or COPD. METHODS: The PubMed, EMBASE, The Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched for randomized controlled trials that involved pharmacist-led interventions among patients with asthma or COPD. We used database-specific vocabulary (eg, Medical Subject Headings) and free text terms expanding from 'asthma', 'COPD' and 'pharmacist' to identify relevant articles. Two reviewers independently selected the studies, assessed the risk of bias and extracted the data. The meta-analysis was performed in Review Manager 5.3 provided by the Cochrane Collaboration. PROSPERO registration number: CRD42019144793. RESULTS AND DISCUSSION: Thirteen studies were eligible for qualitative analysis, and 12 studies were included in the meta-analysis. Pharmacist-led interventions showed a positive effect on medication adherence (1.34 [95% CI 1.18-1.53], P < .0001) and inhalation technique (1.85 [95% CI 1.57-2.17], P < .00001) in COPD and asthma patients. In the subgroup meta-analysis, significant medication adherence improvement was found only in COPD patients (1.41 [1.24-1.61], P < .0001). The subgroup meta-analysis also noted that interventions that included all three Information-Motivation-Behavioural skills (IMB) constructs had a significant improvement in medication adherence (1.41 [1.24-1.61], P < .0001). Subgroup meta-analysis conducted between different diseases, different intervention contents, and different measure tools did not significantly change the heterogeneity. WHAT IS NEW AND CONCLUSION: Pharmacist-led interventions can improve inhalation technique in adult asthma and COPD patients. Significant improvement in medication adherence was found only in COPD patients. The effect among asthmatic patients requires further study. Interventions based on the IMB model may be worthy of clinical promotion and application. More future research is needed to establish solid evidence base for effective interventions and uniform measurement of medication adherence.

5.
Int J Clin Pharmacol Ther ; 58(1): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31319907

RESUMO

OBJECTIVE: To establish a population pharmacokinetic (PopPK) model of cyclosporine A (CsA) in Chinese patients with nephrotic syndrome (NS) and to use the model to guide the adjustment of individualized dosage regimens. MATERIALS AND METHODS: 216 CsA therapeutic drug monitoring (TDM) concentration observations were collected from 127 Chinese patients with NS. The basic model was developed as a one-compartment PK model with first-order absorption and linear elimination. The first-order conditional estimation (FOCE) method was applied to establish the final model with covariates using NONMEM software. The final model was evaluated through internal validation including goodness-of-fit analysis and bootstrap method as well as external validation using 39 additional PK observations from 35 patients with NS. RESULTS: A PopPK model of CsA was established in Chinese NS patients with influence of body weight on clearance. The internal and external validation results showed that the final model was stable. CONCLUSION: The established population model adequately characterized the PK of CsA in Chinese patients and could support individualized medication during treatment of NS with CsA.


Assuntos
Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Síndrome Nefrótica/tratamento farmacológico , Grupo com Ancestrais do Continente Asiático , China , Humanos , Modelos Biológicos , Software
6.
Br J Clin Pharmacol ; 86(4): 637-645, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31869429

RESUMO

AIMS: The aim of the present meta-analysis was to evaluate the efficacy and safety of fingolimod in patients with relapsing multiple sclerosis (RMS). METHODS: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for relevant studies. Two authors independently selected the studies, assessed the risk of bias, and extracted the data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. RESULTS: Ten studies met the inclusion criteria. In patients with RMS, fingolimod demonstrated a significantly lower annualized relapse rate (0.5 mg/d: mean difference [95% confidence interval] = -0.22 [-0.29 to -0.14]; 1.25 mg/d: -0.26 [-0.36 to -0.16]; 5 mg/d: -0.41 [-0.72 to -0.10]) than placebo. Fingolimod also exhibited a favorable performance on other magnetic resonance imaging outcomes and improved the quality of life in patients. No significant difference was noted in the prevalence of adverse events between the fingolimod treatment group and the placebo/disease-modifying therapy groups. CONCLUSIONS: Fingolimod may offer benefits for RMS patients and presents an acceptable safety profile.

7.
Eur J Clin Pharmacol ; 76(3): 383-391, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31873765

RESUMO

PURPOSE: The aim of the present study was to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of remimazolam besylate following single ascending dose (SAD) and continuous infusion in healthy Chinese volunteers. METHODS: This was a randomized phase I study conducted in two parts. Part I was a double-blind, placebo- and midazolam-controlled, SAD study among healthy Chinese participants with a remimazolam dose of 0.025-0.4 mg/kg. Part II was an open-label, midazolam-controlled, continuous infusion study. Bispectral index (BIS) monitoring and Modified Observers Assessment of Alertness and Sedation (MOAA/S) score assessment were used to assess the PD properties. RESULTS: The half-life range of remimazolam was from 34.1 ± 8.1 to 59.8 ± 20.5 min in the SAD study. The sedation function was initially observed at the dose of 0.05 mg/kg remimazolam. Doses of ≥ 0.075 mg/kg exerted a peak sedation effect within 1-2 min after injection, resulting in a deeper and more rapid sedation. In the 2 h continuous infusion, remimazolam showed a deeper sedation and more rapid recovery than midazolam. For general anesthesia, an induction dosage of 0.2 mg/kg/min and a maintenance dosage of 1 mg/kg/h can achieve a satisfactory efficacy effect. CONCLUSIONS: Remimazolam was safe and well tolerated in healthy Chinese participants. Based on the phase I clinical study, we suggest that remimazolam besylate demonstrates greater sedation and quicker recovery from sedation than midazolam.

8.
Curr Drug Metab ; 20(13): 1060-1072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31755383

RESUMO

BACKGROUND: Cardiovascular disease has one of the highest mortality rates among all the diseases. Platelets play an important role in the pathogenesis of cardiovascular diseases. Platelet membrane glycoprotein GPIIb/IIIa antagonists are the most effective antiplatelet drugs, and pulaimab is one of these. The study aims to promote individual medication of pulaimab [anti-GPIIb/IIIa F(ab)2 injection] by discovering the pharmacological relationship among the dose, concentration, and effects. The goal of this study is to establish a population pharmacokineticpharmacodynamic model to evaluate the antiplatelet effect of intravenous pulaimab injection. METHODS: Data were collected from 59 healthy subjects who participated in a Phase-I clinical trial. Plasma concentration was used as the pharmacokinetic index, and platelet aggregation inhibition rate was used as the pharmacodynamic index. The basic pharmacokinetics model was a two-compartment model, whereas the basic pharmacodynamics model was a sigmoid-EMAX model with a direct effect. The covariable model was established by a stepwise method. The final model was verified by a goodness-of-fit method, and predictive performance was assessed by a Bootstrap (BS) method. RESULTS: In the final model, typical population values of the parameters were as follows: central distribution Volume (V1), 183 L; peripheral distribution Volume (V2), 349 L; Central Clearance (CL), 31 L/h; peripheral clearance(Q), 204 L/h; effect compartment concentration reaching half of the maximum effect (EC50), 0.252 mg/L; maximum effect value (EMAX), 54.0%; and shape factor (γ), 0.42. In the covariable model, thrombin time had significant effects on CL and EMAX. Verification by the goodness-of-fit and BS methods showed that the final model was stable and reliable. CONCLUSION: A model was successfully established to evaluate the antiplatelet effect of intravenous pulaimab injection that could provide support for the clinical therapeutic regimen.

9.
Schizophr Bull ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603232

RESUMO

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = -0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

10.
Thromb Res ; 181: 127-134, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31401416

RESUMO

OBJECTIVE: Venous thromboembolism (VTE) is a common cardiovascular disease, in which pulmonary embolism (PE) is potentially life-threatening. Accurate biological markers for the early diagnosis of VTE are needed. The purpose of this study was to analyze and validate the predictive value of microRNAs for the diagnosis of VTE. METHODS: A comprehensive literature review was conducted using the PubMed, Embase, and Cochrane Library databases and is current through Sep 27, 2018. The diagnostic value of microRNAs for VTE was analyzed by creating a summary receiver operating characteristic curve (SROC) and calculating the area under the curve (AUC). RESULTS: Our analysis included 12 articles assessing a total of 1057 individuals. The most frequently researched microRNA was miR-134, and the pooled results of the predictive ability of this miRNA with 95% confidence intervals (CIs) showed an average sensitivity of 0.82 (0.69-0.91) and an average specificity of 0.83 (0.68-0.92). The average AUC for the SROC curves was 0.89 (0.86-0.92). For other microRNAs, AUC values >0.8 were considered as potential diagnostic indices. These microRNAs included miR-1233, miR-134, miR-145, miR-483-3p, miR-582, miR-532, and miR-195. CONCLUSIONS: MicroRNAs may act as novel diagnostic biomarkers for VTE, and miR-1233, miR-134, miR-145, miR-483-3p, miR-582, miR-532, and miR-195 are prime candidates. Of these, research on miR-134 is the most extensive and reliable.


Assuntos
MicroRNA Circulante/metabolismo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Humanos , Tromboembolia Venosa/patologia
11.
BMC Infect Dis ; 19(1): 583, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277607

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients. METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were considered as estimates of the effect. RESULTS: The meta-analysis included 17 studies that assessed a total of 4273 patients. First, carriers of HLA-A *24 were associated with an increased risk of hypersensitivity among patients with HIV who received antiretroviral therapy (OR: 12.12; P = 0.018). Second, five SNPs of HLA-B genotypes, including *18 (OR: 1.63; P = 0.028), *35 (OR: 2.31; P = 0.002), *39 (OR: 11.85; P = 0.040), *51 (OR: 1.66; P = 0.028), and *81 (OR: 8.11; P = 0.021), were associated with an increased risk of hypersensitivity. Conversely, carriers of HLA-B *15 were associated with a reduced risk of hypersensitivity (OR: 0.43; P < 0.001). Third, HLA-C *04 was associated with an increased risk of hypersensitivity (OR: 3.09; P < 0.001), whereas a lower risk for hypersensitivity was observed in patients who were carriers of HLA-C *02 (OR: 0.22; P = 0.030), *03 (OR: 0.53; P = 0.049), and *07 (OR: 0.61; P = 0.044). Finally, carriers of HLA-DRB1 *05 (OR: 0.18; P = 0.006) and *15 (OR: 0.23; P = 0.013) were associated with a reduced risk of hypersensitivity among patients receiving antiretroviral therapy. CONCLUSIONS: The findings of this meta-analysis indicated patients carrying HLA-A *24, HLA-B *18, *35, *39, *51, *81, HLA-C *04 were associated with a higher risk of hypersensitivity. Conversely, subjects carrying HLA-B *15, HLA-C *02, *03, *07, HLA-DRB1 *05, *15 were associated with a reduced risk of hypersensitivity.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Hipersensibilidade a Drogas/genética , Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/efeitos adversos , Didesoxinucleosídeos/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Razão de Chances
12.
Medicine (Baltimore) ; 98(14): e15088, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946364

RESUMO

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations.Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing).Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher trough SDC (1.20 ±â€Š0.50 ng/mL) than recommended trough SDC for heart failure patients. Trough SDC was not significantly influenced by mutations of OATP1B1 388A>G (P = .890), 521T>C (P = .054), and OATP1B3 699G>A (P = .854). Patients with OATP1B1 521T>C mutant-type carrier had slightly higher trough SDC (0.98 ±â€Š0.53 ng/mL) than those with wild-type carrier (0.74 ±â€Š0.40 ng/mL) when they have repaired renal function.Heart failure patients with severe renal dysfunction (GFR<60 mL/min) and/or OATP1B1 521T>C mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring.


Assuntos
Cardiotônicos/sangue , Digoxina/sangue , Taxa de Filtração Glomerular/efeitos dos fármacos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Mutação , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Idoso , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , China , Digoxina/administração & dosagem , Digoxina/efeitos adversos , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Prospectivos
13.
J Clin Pharm Ther ; 44(2): 300-311, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30636182

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Oxcarbazepine (OXC) is a widely used antiepileptic drug whose effect mainly depends on its active metabolite 10-hydroxycarbazepine (MHD). This study established a population pharmacokinetic (PPK) model of MHD in Chinese children with epilepsy and conducted a dosage simulation in order to provide support for individualized OXC treatment. METHODS: Ninety-one plasma sampling points from 88 paediatric patients were retrospective collected. MHD concentrations were detected, and patients' clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modelling approach. The goodness-of-fit (GOF) plots, bootstrap method, prediction-corrected visual predictive check (pcVPC) and normalized prediction distribution errors (NPDE) were performed to evaluate the final model. External model validations by an independent group of paediatric patients (10 patients, 10 blood samples) were conducted. The steady-state trough concentrations of MHD were determined by Monte Carlo simulations for doses ranging from 8 to 60 mg/kg/day. RESULTS: A one-compartment model with first-order elimination successfully described the data. The typical values for MHD clearance (CL/F), distribution volume (V/F) and absorption rate constant (Ka) were 3.25 L/h/70 kg, 151.41 L/70 kg and 0.598 h-1 , respectively. The CL/F and V/F of MHD were related to body weight (WT) via an empirical allometric model. Internal and external validations demonstrated a good predictability of the final model. Monte Carlo simulations revealed that for most paediatric patients, a dosing regimen of 20-30 mg/kg/d bid maybe sufficient to reach MHD therapeutic range. WHAT IS NEW AND CONCLUSION: A PPK model of MHD in Chinese paediatric patients was successfully established. A priori dosing guideline was proposed considering WT and MHD plasma concentrations, providing a basis for OXC dosage calculations and adjustments in Chinese epileptic children.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Modelos Biológicos , Oxcarbazepina/administração & dosagem , Adolescente , Anticonvulsivantes/farmacocinética , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Método de Monte Carlo , Dinâmica não Linear , Oxcarbazepina/farmacocinética , Guias de Prática Clínica como Assunto , Medicina de Precisão , Estudos Retrospectivos
14.
Medicine (Baltimore) ; 97(45): e12996, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407287

RESUMO

OBJECTIVES: Although platinum-based chemotherapy is widely used for advanced ovarian cancer (OC), genetic polymorphisms can influence the chemotherapeutic response. This study investigated the association between XRCC1 polymorphisms Arg194Trp, Arg280His, and Arg399Gln, and overall survival (OS) in OC patients who received platinum-based chemotherapy. METHODS: We systematically searched PubMed, Embase, the Cochrane library, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases for relevant studies from inception to October, 2017. OS was calculated using a random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. RESULTS: Five studies involving 1159 OC patients were included. When compared with 194ArgArg, 194TrpTrp (hazard ratio [HR] 1.09, 95% confidence interval [CI] 0.71-1.69, P = .69) and 194TrpArg (HR 1.00, 95% CI 0.78-1.28, P = .98) carriers were not associated with OS. Similarly, compared with 280ArgArg carriers, neither 280HisHis (HR 1.39, 95% CI 0.82 to -2.34, P = .22) nor 280HisArg (HR 0.98, 95% CI 0.73 to -1.31, P = .90) affected OS. Furthermore, there were no significant differences in OS between 399GlnGln (HR 1.00, 95% CI 0.46-2.16, P > .99), 399GlnArg (HR 1.05, 95% CI 0.81-1.37, P = .70), and 399ArgArg. Finally, subgroup analysis suggested that 399GlnGln significantly decreased OS when the percentage of III or IV cases was >80.0% (HR 1.79, 95% CI 1.22-2.62, P = .003), while OS was increased when this percentage was <80.0% (HR 0.47, 95% CI 0.28-0.79, P = .004). CONCLUSIONS: This study indicated that XRCC1 Arg194Trp, Arg280His, and Arg399Gln did not affect OS after platinum-based chemotherapy in OC patients. However, disease status could affect the relationship between Arg399Gln and OS in these patients.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas , Compostos de Platina/uso terapêutico , Polimorfismo de Nucleotídeo Único , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Modelos de Riscos Proporcionais , Resultado do Tratamento
15.
Zhongguo Zhong Yao Za Zhi ; 43(17): 3498-3505, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30347918

RESUMO

A total of twenty-two compounds were isolated from the 95% EtOH extract of Eclipta prostrata by various purification steps, and their structures were established as ecliptalignin A (1),ecliptasaponin Ⅰ (2), ecliptasaponin Ⅱ (3), echinocystic acid (4), 3-oxo-16α-hydroxy-olean-12-en-28-oic acid (5), acacetin-7-O-rutinoside (6), luteoloside (7), apigenin (8), luteolin (9), acacetin (10), skullcapflavone Ⅱ (11), kaempferol (12), kaempferide (13), quercetin (14), 4',7-dihydroxyl-3',6'-dimethoxylisoflavone-7-O-glucoside (15), ecliptal (16), 5-hydroxymethyl-(2,2',5',2″)-terthienyl tiglate (17), psoralen (18), isopsoralen (19), wedelolactone (20), crinumaquine (21), and 2,3,9,12-tetramethoxyprotoberberine (22) mainly based on the spectroscopic techniques, of which 1 was a new lignin analogue, and 5, 6, 10-13, 15, 18, 19, 21 and 22 were isolated form this plant for the first time.


Assuntos
Eclipta/química , Compostos Fitoquímicos/análise , Flavonas/análise , Flavonas/isolamento & purificação , Lignina/análise , Lignina/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Saponinas/análise , Saponinas/isolamento & purificação
16.
Pharmacogenomics J ; 18(6): 721-729, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30250148

RESUMO

Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included. The summary ORs suggested that 521CC (OR: 2.31; 95% CI: 1.15-4.63; P = 0.019), 521TC (OR: 1.34; 95% CI: 1.02-1.76; P = 0.034), and 521CC + TC (OR: 1.82; 95% CI: 1.32-2.51; P < 0.001) were associated with a greater risk of statin-induced myopathy than 521TT. The higher incidence of statin-induced myopathy was found to be significantly correlated with the C allele compared with the T allele (OR: 1.89; 95% CI: 1.36-2.62; P < 0.001). In addition, we observed that 521CC + TC was associated with an increased risk of myopathy in individuals who received simvastatin (OR: 2.35; 95% CI: 1.08-5.12; P = 0.032) or rosuvastatin (OR: 1.69; 95% CI: 1.07-2.67; P = 0.024) when compared with 521TT. The 521C allele was associated with a greater risk of cerivastatin-induced myopathy than the T allele (OR: 1.95; 95% CI: 1.47-2.57; P < 0.001). The findings of this study indicated that SLCO1B1 T521C was associated with a significantly higher risk of statin-induced myopathy, especially for simvastatin, rosuvastatin, and cerivastatin. Future studies should be conducted in subjects receiving specific types of drugs, and any potential adverse events need to be explored.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Doenças Musculares/induzido quimicamente , Doenças Musculares/genética , Variantes Farmacogenômicos , Polimorfismo Genético , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico , Farmacogenética , Piridinas/efeitos adversos , Medição de Risco , Fatores de Risco , Rosuvastatina Cálcica/efeitos adversos , Sinvastatina/efeitos adversos
17.
Patient Prefer Adherence ; 12: 1273-1278, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050289

RESUMO

Background: The objective of this study was to evaluate the impact of pharmaceutical care on the knowledge, adherence, and efficacy of hormone therapy in climacteric women participated in multidisciplinary collaborative clinic, launched by Peking University First Hospital (Beijing, People's Republic of China) in 2012. Methods: A total of 296 patients were recruited (intervention group n=150, control group n=146). The patients in the intervention group visited the multidisciplinary collaborative clinic for their initial hormone therapy, receiving individualized pharmaceutical care (PC), whereas the control group visited only the general clinic without PC. The pill count method, knowledge assessment questionnaire (Cronbach's α=0.80), and the modified Kupperman Index were used to assess the knowledge, adherence, and efficacy at months 3, 6, and 12. Results: The intervention group, which received PC, showed significantly higher and better knowledge, adherence, and efficacy than the control group, demonstrating the effectiveness of the PC provided. The knowledge scores of the intervention and control groups at months 3, 6, and 12 were (73.12 vs 59.28), (77.63 vs 66.19), and (80.81 vs 66.64); the data for adherence were (90.97% vs 82.17%), (93.21% vs 87.79%), and (95.81% vs 93.38%); and the values of the modified Kupperman Index were (17.15 vs 24.05), (13.22 vs 22.01), and (12.21 vs 23.15), respectively. Conclusion: PC improved the knowledge, adherence, and efficacy of hormone therapy in climacteric women. Therefore, the multidisciplinary collaborative model investigated in our study should be advocated in other health care institutions for the benefit of more patients. Further large-sample and long-term studies should be conducted to evaluate the effects of PC on patient clinical outcomes, including its impact on the safety and efficacy of long-term use of hormone therapy, as well as the economic benefits.

18.
Phytomedicine ; 38: 125-134, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29425645

RESUMO

BACKGROUND: Sailuotong (SLT) is a standard Chinese preparation made from extracts of Panax ginseng (ginseng), Ginkgo biloba (ginkgo), and Crocus sativus (saffron). Preliminary clinical trials and animal experiments have demonstrated that SLT could improve cognition of vascular dementia (VD). PURPOSE: To avoid incident drug-drug interaction which is easily encountered in patients of VD, the potential influence of SLT on main drug-metabolic cytochromes P450 enzymes (CYP450) was investigated. METHOD: A "cocktail probes" approach was employed to evaluate the activities of CYP450. A rapid and selective analysis method was developed to examine 5 CYP probe drugs and their specific metabolites in plasma by using online SPE followed by a single LC-MS/MS run. After pretreatment for 2 weeks with SLT, ginseng, gingko, saffron or water (control), a cocktail solution containing caffeine, losartan, omeprazole, dextromethorphan and midazolam was given to rats orally. The plasma was obtained at different time intervals and then measured for the concentration of probes and their metabolites using developed SPE-LC-MS/MS method. Activity of five isozymes was estimated by comparing plasma pharmacokinetics of substrates and their metabolites (caffeine/paraxanthine for CYP1A2, losartan/E-3174 for CYP2C11, omeprazole/5-hydroxyl omeprazole for CYP2C6, dextromethorphan/dextrophan for CYP2D2 and midazolam/1-hydroxyl midazolam for CYP3A1/2) between control and drug treatment groups. RESULT: Compared with control group, repeated administration of SLT induced CYP1A2 by enhancing AUC paraxanthine / AUC caffeine to144%. The influence is attributed to its herbal component of ginseng to a large extent. Meanwhile, metabolic ability towards losartan was significantly elevated in SLT and gingko group by 31% and 25% respectively, indicating weak induction of CYP2C11 in rats. The analysis on probes of omeprazole and dextromethorphan showed a lack of influence on CYP 2C6 and CYP2D2 in all treated groups. In terms of CYP3A1/2, SLT decreased AUC ratio of 1-hydroxyl midazolam to midazolam by 39% and extended the half-life of midazolam apparently. Besides, significantly decreased systematic exposure of midazolam suggested the inhibition on metabolism of CYP3A1/2 is likely secondary to the interaction on absorption at intestinal level. The inhibition of SLT on CYP3A was likely attributed to ginseng and gingko cooperatively. CONCLUSION: Further observation on herb-drug interaction should be considered during clinical application of SLT.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Interações Ervas-Drogas , Animais , Cafeína/sangue , Cafeína/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Meia-Vida , Losartan/farmacocinética , Masculino , Midazolam/sangue , Midazolam/farmacocinética , Omeprazol/farmacocinética , Ratos Wistar
19.
Biol Open ; 6(8): 1130-1136, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28642243

RESUMO

Osteoarthritis (OA) is a common and dynamic disease of the joints, including the articular cartilage, underlying bones and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec) is known to affect many biological processes; however, its effects on articular chondrocytes remain unclear. This study aimed to assess the effects of Tec on articular cartilage. In vitro, Tec inhibited the expression levels of type X collagen, cyclooxigenase-2, matrix metalloproteinase (MMP)-3 and MMP-13, but enhanced the expression of Runx1, type II collagen and aggrecan in the presence of IL-1ß. Meanwhile, Tec inhibited apoptosis through the Bax/Bcl-2/caspase-3 pathway, upregulating p-Bad, downregulating the Bax/Bcl-2 ratio, and activating caspase-3 compared with IL-1ß treatment only. Moreover, this process was partially regulated by NF-κB P65. In vivo, the chondroprotective effects of Tec were assessed by establishing a model of surgically induced OA. Tec-treated joints exhibited fewer osteoarthritic changes than saline-treated joints. Meanwhile, 1.5 µg/kg Tec treatment produced a greater protective effect than 0.75 µg/kg Tec. The Osteoarthritis Research Society International (OARSI) scoring system, employed to assess histopathological grading of the models, as well immunohistochemistry for Aggrecan Neoepitope and MMP-3, further confirmed the results. In conclusion, this study showed that Tec plays a chondroprotective role in the OA process by preventing articular cartilage degeneration and chondrocyte apoptosis via the NF-κB P65 pathway.

20.
Pharmacotherapy ; 37(7): e71-e75, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28543284

RESUMO

Oxcarbazepine is a second-generation antiepileptic drug that is used to treat partial seizures. Although it has been increasingly used in pregnant women, its fetal safety has not been fully validated. We describe a 12-hour-old neonate who developed neonatal abstinence syndrome (NAS) after intrauterine exposure to oxcarbazepine. The neonate was born via cesarean section to a mother who took oxcarbazepine 300 mg/day for treatment of seizures throughout her pregnancy. Approximately 12 hours after birth, the infant developed paroxysmal jitter, which mainly presented as increased excitability, irritability, limb shaking, and increased muscle tone. These symptoms resolved by day 9 of life. Although NAS occurs most often after in utero exposure to opioids, exposure to other drugs during pregnancy may contribute to a small proportion of NAS cases. To our knowledge, this is the second case report of oxcarbazepine-induced NAS. Pregnant women with epilepsy should weigh the pros and cons of continuing oxcarbazepine during their pregnancy when they are prescribed this drug. For infants with in utero oxcarbazepine exposure, comprehensive assessments and examinations are necessary for screening oxcarbazepine-induced NAS.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/análogos & derivados , Síndrome de Abstinência Neonatal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adulto , Anticonvulsivantes/sangue , Carbamazepina/efeitos adversos , Carbamazepina/sangue , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome de Abstinência Neonatal/sangue , Oxcarbazepina , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue
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