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In multi-regional clinical trials, hierarchical linear models have been actively studied because they can reflect that patients in the same region share common intrinsic and extrinsic factors. In this paper, we investigate the statistical properties of the hierarchical linear model including a random effect in the intercept. The big advantage of the random intercept hierarchical linear model is that it can control the type I error rates of testing the overall treatment effect when there are no or clinically negligible regional differences in the treatment effect. Moreover, we compare the pros and cons with the hierarchical linear model in which the random effect is included in the slope. For the two hierarchical linear models, the model selection criteria are determined according to the magnitude of the difference in treatment effect across the regions, and we provide the criteria through simulation studies.
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Modelos Lineares , Humanos , Simulação por ComputadorRESUMO
Background and Objectives: Hand grip strength (HGS) and osteoporosis are known to be closely related to the health condition of the elderly, respectively. Comprehensive studies including adults over middle age were insufficient. This study aimed to investigate the relationship between HGS with osteoporosis and health-related quality of life (HRQoL) in adults aged >40 years. Materials and Methods: This cross-sectional analysis included data from 13,966 people aged >40 years between 2015 to 2018 provided by the Korea National Health and Nutrition Examination Survey. The HGS was divided into strong and weak quartiles, defined as the highest and lowest quartiles, respectively. We used the European Quality of Life Scale-Five dimensions (EQ-5D) for HRQoL. We performed multiple logistic regression and post hoc analysis to confirm the relationship between the four groups and HRQoL. Results: Osteoporotic patients with weak HGS showed the lowest EQ-5D index (0.87 ± 0.01) among all groups and had a significantly impaired HRQoL in all EQ-5D dimensions, at least 1.75 times more than healthy individuals with strong HGS (0.95 ± 0.00). Osteoporotic patients with weak HGS showed, notably, 2.68 times more impaired mobility compared to healthy individuals with strong HGS among all five dimensions of the EQ-5D. In self-care, significant sex differences in impaired HRQoL were observed (males 6.03, 2.23-16.35; females 2.51, 1.70-3.71). Conclusions: Weak HGS and the presence of osteoporosis were associated with low HRQoL, respectively. Middle-aged and older adults with both weak HGS and osteoporosis showed poorer HRQoL compared to healthy middle-aged and older adults. This suggests that HGS is a possible factor for predicting poor HRQoL in adults aged >40 years with or without osteoporosis. It is necessary to assess the risk of low HRQoL by measuring HGS and confirming whether osteoporosis is accompanied in adults over middle age.
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Osteoporose , Qualidade de Vida , Idoso , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Inquéritos Nutricionais , Força da Mão , Estudos Transversais , Osteoporose/complicações , Osteoporose/epidemiologia , Inquéritos e QuestionáriosRESUMO
This review article sets out to examine the Type I error rates used in noninferiority trials. Most papers regarding noninferiority trials only state Type I error rate without mentioning clearly which Type I error rate is evaluated. Therefore, the Type I error rate in one paper is often different from the Type I error rate in another paper, which can confuse readers and makes it difficult to understand papers. Which Type I error rate should be evaluated is related directly to which paradigm is employed in the analysis of noninferiority trial, and to how the historical data are treated. This article reviews the characteristics of the within-trial Type I error rate and the unconditional across-trial Type I error rate which have frequently been examined in noninferiority trials. The conditional across-trial Type I error rate is also briefly discussed. In noninferiority trials comparing a new treatment with an active control without a placebo arm, it is argued that the within-trial Type I error rate should be controlled in order to obtain approval of the new treatment from the regulatory agencies. I hope that this article can help readers understand the difference between two paradigms employed in noninferiority trials.
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Ensaios Clínicos Controlados como Assunto/métodos , Ensaios Clínicos Controlados como Assunto/estatística & dados numéricos , Interpretação Estatística de Dados , Projetos de Pesquisa , Intervalos de Confiança , Humanos , Modelos Estatísticos , PlacebosRESUMO
A new three-arm parallel design was recently proposed to investigate the biosimilarity between a biological product and a reference product by using the relative distance. The purpose of this article is to extend their results to binary endpoints for three popular metrics: the risk difference, the log relative risk, and the log odds ratio. The relative distances based on the three metrics are defined, and corresponding test procedures are developed. The type I error rates and powers are investigated theoretically and empirically.
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Medicamentos Biossimilares/uso terapêutico , Determinação de Ponto Final/estatística & dados numéricos , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Algoritmos , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/farmacocinética , Humanos , Razão de Chances , Equivalência TerapêuticaRESUMO
The most widely used design for a Phase III comparative study for demonstrating the biosimilarity between a biosimilar product and a renovator biological product is the equivalence trial, whose aim is to show that the difference between two population means of a primary endpoint is less than a prespecified equivalence margin. A well-known sample size formula for the equivalence trial is given by [Formula: see text] Since this formula is obtained based on the approximate power rather than the exact power, we investigate in this article the accuracy of the sample size formula. We conclude that the sample size formula is very conservative. Specifically, we show that the exact power based on the sample size calculated from the formula to have power [Formula: see text] is actually [Formula: see text] under some conditions. Therefore, the use of the sample size formula may cause a huge extra cost to biotechnology companies. We propose that the sample size should be calculated based on the exact power precisely and numerically. The R code to calculate the sample size numerically is provided in this article.
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Medicamentos Biossimilares/uso terapêutico , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Descoberta de Drogas/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Tamanho da Amostra , Medicamentos Biossimilares/farmacocinética , Ensaios Clínicos Fase III como Assunto/métodos , Descoberta de Drogas/métodos , Humanos , Modelos Estatísticos , Equivalência TerapêuticaRESUMO
This pilot study aimed to investigate the immediate impact of low-intensity exercises with blood flow restriction (BFR) on older adults with knee osteoarthritis (KOA). Fifteen patients with KOA who were over 50 years old, participated and underwent low-intensity resistance knee exercises at 30% of their one-repetition maximum with BFR three times/week for two weeks. Pre- and post-exercise assessments included pain levels, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, isokinetic knee strength, lower extremity muscle volume (via leg circumference and muscle thickness), functional performance tests (timed up-and-go [TUG] and sit-to-stand [STS]), skeletal muscle index (SMI) using bioelectrical impedance analysis, and handgrip strength (HGS). Post-exercise, there was a significant reduction in pain. WOMAC scores showed significant improvements across all three domains: pain, stiffness, and physical function. In the TUG and STS tests, completion times were significantly reduced. Thigh and calf circumferences, as well as thigh muscle thickness significantly increased after exercise. Post-exercise SMI and HGS also significantly increased. However, isokinetic knee strength did not show significant changes. In conclusion, low-intensity BFR exercises provide immediate benefits in symptoms and physical performance for patients with KOA, potentially inducing local and systemic muscle mass increase, even after a short-term intervention.
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BACKGROUND: Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with heart failure reduced ejection fraction (HFrEF). This study aimed to assess the relative efficacy of vericiguat and sacubitril/valsartan through a systematic review, network meta-analysis, and non-inferiority tests. METHODS: A systematic review was conducted to identify the randomized phase 3 clinical trials involving vericiguat and sacubitril/valsartan. The hazard ratios (HRs) with 95% confidence intervals (CI) for cardiovascular death (CVD) and hospitalization due to HF (hHF) were extracted from these trials and synthesized via network meta-analysis. Non-inferiority testing of vericiguat was performed using a fixed-margin method with a predefined non-inferiority margin (1.24). Sensitivity analyses explored the impact of the time from hHF to screening. RESULTS: Among the 1366 studies, two trials (VICTORIA and PARADIGM-HF) met the inclusion criteria. Network meta-analysis demonstrated that the HR for CVD or hHF with vericiguat did not significantly differ from that for sacubitril/valsartan (HR: 0.88, 95% CI:0.62-1.23). The upper limit of the 95% CI was less than the predefined margin of 1.24, confirming vericiguat's non-inferiority to sacubitril/valsartan. Sensitivity analyses affirmed the robustness of the base-case results. CONCLUSION: Vericiguat exhibited a comparable risk of CVD or hHF when contrasted with sacubitril/valsartan. Importantly, in patients with HFrEF, vericiguat's efficacy was not statistically inferior to that of sacubitril/valsartan. These findings reinforce the potential of vericiguat as a viable treatment option for this patient population.
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca , Metanálise em Rede , Volume Sistólico , Tetrazóis , Valsartana , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Aminobutiratos/uso terapêutico , Humanos , Volume Sistólico/fisiologia , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Pirimidinas/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Compostos Heterocíclicos com 2 AnéisRESUMO
In this paper, we propose a new three-arm parallel design to investigate biosimilarity between a biosimilar product and an innovator biological product by using relative distance based on the absolute mean differences. In the proposed design, one arm is for the biosimilar product and the other two arms are for the innovator biological product. The distance between the biosimilar product and the innovator biological product is defined by the absolute mean different between two products. Similarly, the distance between the innovator biological products from two difference batches is defined. The relative distance is defined as the ratio of the two distances whose denominator is the distance between the innovator biological products from two different batches. In the proposed design, if the relative distance is less than a prespecified margin, we claim that the two products are claimed to be biosimilar. The statistical test based on the ratio estimator and the linearization method are developed to assess biosimilarity. The power functions of two tests are derived in large sample and compared numerically. Because the statistical test based on the ratio estimator is more powerful than the linearization method, we recommend the statistical test based on the ratio estimator.
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Algoritmos , Medicamentos Biossimilares/análise , Avaliação de Medicamentos/estatística & dados numéricosRESUMO
This article deals with the dependency(ies) of noninferiority test(s) when the two confidence interval method is employed. There are two different definitions of the two confidence interval method. One of the objectives of this article is to sort out some of the confusion in these two different definitions. In the first definition the two confidence interval method is considered as the fixed margin method that treats a noninferiority margin as a fixed constant after it is determined based on historical data. In this article the method is called the two confidence interval method with fixed margin. The issue of the dependency(ies) of noninferiority test(s) does not occur in this case. In the second definition the two confidence interval method incorporates the uncertainty associated with the estimation for the noninferiority margin. In this article the method is called the two confidence interval method with random margin. The dependency(ies) occurs, because the two confidence interval method(s) with random margin shares the same historical data. In this article we investigate how the dependency(ies) affects the unconditional and conditional across-trial type I error rates.
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Intervalos de Confiança , Ensaios Clínicos Controlados Aleatórios como Assunto , Aprovação de Drogas , HumanosRESUMO
A thorough QT trial is typically designed to test for two sets of hypotheses. The primary set of hypotheses is for demonstrating that the test treatment will not prolong QT interval. The second set of hypotheses is to demonstrate the assay sensitivity of the positive control treatment in the study population. Both analyses require multiple comparisons by testing the treatment difference measured repeatedly at multiple selected time points. Tsong and Zhong (2010) indicated that for prolongation testing, this involves an intersection-union test that leads to the reduction of study power. It requires type II error rate adjustment in order to maintain proper sample size and power of the test. Tsong et al. (2010) indicated also that the assay sensitivity analysis is carried out using a union-intersection test that leads to the inflation of the family-wise type I error rate. Type I error rate adjustment is required to control the family-wise type I error rate. Zhang and Machado (2008) proposed the sample size calculation of test-placebo QT response difference based on simulation with a multivariate normal distribution model. Even though the results are generally used as guidance for sample size determination for balanced arm TQT trials, they are limited in generalization to various advanced and adaptive designs of TQT trials (Zhang, 2011 ; Tsong, 2013). In this article, we propose a power equation based on multivariate normal distribution of TQT trials. Sample sizes of various TQT designs can be obtained through numerical iteration of the equation.
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Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Humanos , Tamanho da AmostraRESUMO
BACKGROUND: Korean ginseng (Panax ginseng C.A. Meyer) has been used as a botanical medicine throughout the history of Asian traditional Oriental medicine. Formulated red ginseng (one form of Korean ginseng) has been shown to have antioxidant and chemopreventive effects. METHODS: This study investigated the cytoprotective effects and mechanism of action of Korean red ginseng extract (RGE) against severe ROS production and mitochondrial impairment in a cytotoxic cell model induced by AA + iron. RESULTS: RGE protected HepG2 cells from AA + iron-induced cytotoxicity by preventing the induction of mitochondrial dysfunction and apoptosis. Moreover, AA + iron-induced production of ROS and reduction of cellular GSH content (an important cellular defense mechanism) were remarkably attenuated by treatment with RGE. At the molecular level, treatment with RGE activated LKB1-dependent AMP-activated protein kinase (AMPK), which in turn led to increased cell survival. The AMPK pathway was confirmed to play an essential role as the effects of RGE on mitochondrial membrane potential were reversed upon treatment with compound C, an AMPK inhibitor. CONCLUSIONS: Our results demonstrate that RGE has the ability to protect cells from AA + iron-induced ROS production and mitochondrial impairment through AMPK activation.
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Proteínas Quinases Ativadas por AMP/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mitocôndrias/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Substâncias Protetoras/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , RatosRESUMO
This paper proposes low-melting-point eutectic salts containing RbCl as electrolytes for light weight thermal batteries. The handleability of the eutectic salts was remarkably improved for commercialisation. Their performance as thermal battery molten-salt electrolytes was verified using tests on a single cell and a 12-cell stacked battery.
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A regulatory agency usually requires two independent positive trials of the same new drug for approval. If two different new drugs are approved with the λ-margin approach by using the same active control, it implies that four noninferiority trials share the same active control. Sharing the same active control generates dependencies among trials. In this paper we investigate how much such dependencies inflate the unconditional and conditional across-trial type I error rates, and we propose a new procedure to adjust the inflated unconditional across-trial type I error rates.
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Ensaios Clínicos Controlados como Assunto/métodos , Ensaios Clínicos Controlados como Assunto/estatística & dados numéricos , Aprovação de Drogas , Modelos Estatísticos , Projetos de Pesquisa/estatística & dados numéricos , Ensaios Clínicos como Assunto/métodosRESUMO
Haplotype, which is the sequence of SNPs in a specific chromosome, plays an important role in disease association studies. However, current sequencing techniques can detect the presence of SNP sites, but they cannot tell which copy of a pair of chromosomes the alleles belong to. Moreover, sequencing errors that occurred in sequencing SNP fragments make it difficult to determine a pair of haplotypes from SNP fragments. To help overcome this difficulty, the haplotype assembly problem is defined from the viewpoint of computation, and several models are suggested to tackle this problem. However, there are no freely available web-based tools to overcome this problem as far as we are aware. In this paper, we present a web-based application based on the genetic algorithm, named HapAssembler, for assembling a pair of haplotypes from SNP fragments. Numerical results on real biological data show that the correct rate of the proposed application in this paper is greater than 95% in most cases. HapAssembler is freely available at http://alex.chonnam.ac.kr/~drminor/hapHome.htm. Users can choose any model among four models for their purpose and determine haplotypes from their input data.
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Algoritmos , Haplótipos , Internet , Polimorfismo de Nucleotídeo Único , HumanosRESUMO
In non-inferiority trials that employ the synthesis method several types of dependencies among test statistics occur due to sharing of the same information from the historical trial. The conditions under which the dependencies appear may be divided into three categories. The first case is when a new drug is approved with single non-inferiority trial. The second case is when a new drug is approved if two independent non-inferiority trials show positive results. The third case is when two new different drugs are approved with the same active control. The problem of the dependencies is that they can make the type I error rate deviate from the nominal level. In order to study such deviations, we introduce the unconditional and conditional across-trial type I error rates when the non-inferiority margin is estimated from the historical trial, and investigate how the dependencies affect the type I error rates. We show that the unconditional across-trial type I error rate increases dramatically as does the correlation between two non-inferiority tests when a new drug is approved based on the positive results of two non-inferiority trials. We conclude that the conditional across-trial type I error rate involves the unknown treatment effect in the historical trial. The formulae of the conditional across-trial type I error rates provide us with a way of investigating the conditional across-trial type I error rates for various assumed values of the treatment effect in the historical trial.
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Ensaios Clínicos Controlados como Assunto/métodos , Interpretação Estatística de Dados , Simulação por Computador , HumanosRESUMO
BACKGROUND AND OBJECTIVES: The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes. METHODS: We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI. RESULTS: Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE. CONCLUSIONS: Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry.
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PURPOSE: Dyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD. METHODS: This multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150-500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non-HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment. FINDINGS: The difference in the mean percentage change in non-HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was -12.45% (95% CI, -17.18 to -7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non-HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. IMPLICATIONS: In these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non-HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.
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Dislipidemias/tratamento farmacológico , Fenofibrato/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Apolipoproteínas B/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , República da Coreia , Triglicerídeos/sangueRESUMO
BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (-29.8% vs. 3.6%, P<0.001) and non-HDL-C (-10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.
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Atorvastatina/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertrigliceridemia/tratamento farmacológico , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
In this study, we fabricated a cathode with lower amounts of additive materials and higher amounts of active materials than those of a conventional cathode. A thermal battery was fabricated using FeS2 treated foam as the cathode frame, and its feasibility was verified. X-ray diffraction, transmission electron microscopy, and scanning electron microscopy were used to analyze the effects of thermal sulfidation temperature (400 and 500°C) on the structure and surface morphology of the FeS2 foam. The optimal temperature for the fabrication of the FeSx treated foam was determined to be 500°C. The FeS2 treated foam reduced the interfacial resistance and improved the mechanical strength of the cathode. The discharge capacity of the thermal battery using the FeS2 treated foam was about 1.3 times higher than that of a thermal battery using pure Fe metal foam.
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A bioequivalence study is usually conducted with the same-day drug administration. However, hospitalization is occasionally separated for logistical, operational, or other reasons. Recently, there was a case of separate hospitalization because of difficulties in subject recruitment. This article suggests a better way of bioequivalence data analysis for the case of separate hospitalization. The key features are (1) considering the hospitalization date as a random effect than a fixed effect and 2) using "PROC MIXED" instead of "PROC GLM" to include incomplete subject data.