• Communications for Statistical Applications and Methods
• /
• v.27 no.6
• /
• pp.675-688
• /
• 2020

In survival analysis of observational data, the inverse probability weighting method and the Cox proportional hazards model are widely used when estimating the causal effects of multiple-valued treatment. In this paper, the two kinds of weights have been examined in the inverse probability weighting method. We explain the reason why the stabilized weight is more appropriate when an inverse probability weighting method using the generalized propensity score is applied. We also emphasize that a marginal hazard ratio and the conditional hazard ratio should be distinguished when defining the hazard ratio as a treatment effect under the Cox proportional hazards model. A simulation study based on real data is conducted to provide concrete numerical evidence.

• The Korean Journal of Applied Statistics
• /
• v.32 no.2
• /
• pp.173-185
• /
• 2019

Causal questions are prevalent in scientific research, for example, how effective a treatment was for preventing an infectious disease, how much a policy increased utility, or which advertisement would give the highest click rate for a given customer. Causal inference theory in statistics interprets those questions as inferring the effect of a given intervention (treatment or policy) in the data generating process. Causal inference has been used in medicine, public health, and economics; in addition, it has received recent attention as a tool for data-driven decision making processes. Many recent datasets are observational, rather than experimental, which makes the causal inference theory more complex. This review introduces key concepts and recent trends of statistical causal inference in observational studies. We first introduce the Neyman-Rubin's potential outcome framework to formularize from causal questions to average treatment effects as well as discuss popular methods to estimate treatment effects such as propensity score approaches and regression approaches. For recent trends, we briefly discuss (1) conditional (heterogeneous) treatment effects and machine learning-based approaches, (2) curse of dimensionality on the estimation of treatment effect and its remedies, and (3) Pearl's structural causal model to deal with more complex causal relationships and its connection to the Neyman-Rubin's potential outcome model.

• Journal of Powder Materials
• /
• v.4 no.3
• /
• pp.222-229
• /
• 1997

A P/M high speed steel of ASP 30 grade was austenitized, gas quenched and tempered at various conditional. The mechanical properties such as hardness, bend strength and fracture toughness were evaluated after heat treatment. The microstructure and the type and volume fraction of carbides were analyzed by an optical microscope, image analyzer and XRD. The primary carbides after the heat treatment were MC and $M_6C$ type. The volume of the total carbide varied from 10 to 15% depending on the austenitizing and tempering temperature. The tempering temperature for maximum hardness was at around 52$0^{\circ}C$. But the maximum bend strength was obtained at about 55$0^{\circ}C$. The fracture toughness was largely affected by the presence of retained austenite after gas quenching and secondary hardening during tempering.

• Communications for Statistical Applications and Methods
• /
• v.30 no.6
• /
• pp.631-652
• /
• 2023

In the two-condition within-subject mediation design, pairs of variables such as mediator and outcome are observed under two treatment conditions. The main objective of the design is to investigate the indirect effects of the condition difference (sum) on the outcome difference (sum) through the mediator difference (sum) for comparison of two treatment conditions. The natural condition variables mean the original variables, while the rotated condition variables mean the difference and the sum of two natural variables. The outcome difference (sum) is expressed as a linear model regressed on two natural (rotated) mediators as a parallel two-mediator design in two condition approaches: the natural condition approach uses regressors as the natural condition variables, while the rotated condition approach uses regressors as the rotated condition variables. In each condition approach, the total indirect effect on the outcome difference (sum) can be expressed as the sum of two individual indirect effects: within- and cross-condition indirect effects. The total indirect effects on the outcome difference (sum) for both condition approaches are the same. The invariance of the total indirect effect makes it possible to analyze the nature of two pairs of individual indirect effects induced from the natural conditions and the rotated conditions. The two-condition within-subject design is extended to the addition of a between-subject moderator. Probing of the conditional indirect effects given the moderator values is implemented by plotting the bootstrap confidence intervals of indirect effects against the moderator values. The expected indirect effect with respect to the moderator is derived to provide the overall effect of moderator on the indirect effect. The model coefficients are estimated by the structural equation modeling approach and their statistical significance is tested using the bias-corrected bootstrap confidence intervals. All procedures are evaluated using function lavaan() of package {lavaan} in R.

• Tuberculosis and Respiratory Diseases
• /
• v.83 no.1
• /
• pp.20-30
• /
• 2020

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only firs-tline drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

• Journal of Haehwa Medicine
• /
• v.16 no.2
• /
• pp.199-210
• /
• 2007

Objective & Methods : The case report is to observe 27 case of venesection with negative pressure therapy(buhang) operated at CV17 (Danjuong) on sudden palpitation. We carried out to analyze the distribution and Martin's evaluation and weighted scale by sex & age, patient conditional grade, accompanied symptoms, duration, number of treatments as well. Results : 1. Forties is significantly distributed on sudden palpitation. 2. Depression instance out of many accompanied symptoms is significantly distributed. 3. Mean of operant frequency is significantly resulted on 10 or 11 times. 4. The improvement on the weighted scale is over one grade. 5. Younger is high on the assessment of treatment on Martin's evaluation and weighted scale by age, while older is low. 6. Lesser one year and more three years is some significantly resulted on the assessment of treatment on Martin's evaluation and weighted scale by duration. 7. Pleurodynia, insomnia, distress in the stomach are effective more 90%, and depression, asthma are more 80% on the assessment of treatment on Martin's evaluation by accompanied symptoms, while asthma and pleurodynia are very significantly resulted on the assessment of treatment on weighted scale. 8. The assessment of treatment on Martin's evaluation and weighted scale have no connection with operant frequency. Conclusion : These results suggest that venesection with negative pressure therapy(buhang) operated at CV17 (Danjuong) has a therapeutic effect on on sudden palpitation.

• Korean Journal of Clinical Pharmacy
• /
• v.26 no.4
• /
• pp.312-317
• /
• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Archives of Plastic Surgery
• /
• v.50 no.4
• /
• pp.432-442
• /
• 2023

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

• The Korean Journal of Applied Statistics
• /
• v.36 no.5
• /
• pp.381-397
• /
• 2023

The most representative design used in clinical trials is randomization, which is used to accurately estimate the treatment effect. However, comparison between the treatment group and the control group in an observational study without randomization is biased due to various unadjusted differences, such as characteristics between patients. Propensity score weighting is a widely used method to address these problems and to minimize bias by adjusting those confounding and assess treatment effects. Inverse probability weighting, the most popular method, assigns weights that are proportional to the inverse of the conditional probability of receiving a specific treatment assignment, given observed covariates. However, this method is often suffered by extreme propensity scores, resulting in biased estimates and excessive variance. Several alternative methods including trimming, overlap weights, and matching weights have been proposed to mitigate these issues. In this paper, we conduct a simulation study to compare performance of various propensity score weighting methods under diverse situation, such as limited overlap, misspecified propensity score, and treatment contrary to prediction. From the simulation results overlap weights and matching weights consistently outperform inverse probability weighting and trimming in terms of bias, root mean squared error and coverage probability.

• Korean Journal of Animal Reproduction
• /
• v.27 no.3
• /
• pp.187-195
• /
• 2003

This study was carried out to improve of enucleation efficiency on porcine recipient oocytes preactivated. In ethanol or $Ca^{2+}$ ionophore, effect of repeating and combinational activation with 6-DMAP or cycloheximide compared with alone activated treatment. Recipient oocytes's activation by $Ca^{2+}$ ionophore combined with 6-DMAP or cycloheximide were significantly higher than alone treatment(P<0.05). Between repeating and alone treatments were not significantly different. In ethanol, repeating treatment was significantly lower than alone(P<0.05), and combination treatments were not significantly different. On the basis of these results, efficiency of enucleation, electrical fusion and in vitro development compared preactivated with non-preactivated recipient oocytes. Enucleation and fusion rates of preactivated oocytes were improved significantly compared with non-preactivated oocytes(90.7%, 71.8 vs 77.8%, 61.1%; P<0.05). Behind the back, cleavage and in vitro development rates were significantly lower than non-preactivated oocytes(38.7%, 19.3% vs 68.8%, 30.6%; P<0.05).