Beyond One-Size-Fits-All: Tailoring Teicoplanin Regimens for Normal Renal Function Patients Using Population Pharmacokinetics and Monte Carlo Simulation.

In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.

Clinical and functional outcomes of TKA after HTO or UKA: a New Zealand Joint Registry Study.

INTRODUCTION: Surgical options for patients with unicompartmental knee osteoarthritis include high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA). When managing younger patients with a higher chance of further surgery, the outcome of any subsequent conversion to total knee arthroplasty (TKA) also needs to be considered. The aim of this study was to compare implant survivorship and patient-reported outcomes for patients undergoing TKA after previous HTO or UKA, with comparisons for age, gender and comorbidities. METHODS: Revision risk and 6-month Oxford Knee Scores (OKS) from the New Zealand Joint Registry were compared for patients who underwent TKA after HTO (HTO-TKA; n = 1556) or UKA (UKA-TKA; n = 965) between 1999 and 2019, with a comparison group of primary TKA (n = 110,948). Mean follow-up was 8.2 years. RESULTS: Adjusted revision risk was similar for HTO-TKA and UKA-TKA groups (hazard ratio (HR) 1.04, p = 0.84); and risk for both groups were higher than primary TKA (HTO-TKA HR 1.45, p = 0.002; UKA-TKA HR 1.51, p = 0.01). Overall adjusted mean OKS at 6 months for HTO-TKA (36.2) was similar to primary TKA (36.8, p = 0.23); and both were higher than UKA-TKA (34.2, p < 0.001). For the youngest patient group (< 55 years), revision rates of UKA-TKA were two-fold higher than HTO-TKA (2.8 vs. 1.3 per 100 component yrs, p < 0.03). HTO-TKA had better OKS (37.5 vs. 34.1, p < 0.0001) for males. Mean OKS for UKA-TKA was lower than HTO-TKA for patients with ASA 1-2 (35.6 vs. 37.5, p < 0.01). CONCLUSION: The findings from this study suggest that revision rate following TKA after HTO and UKA are similar. However, TKA after HTO have superior functional outcomes compared with TKA after UKA and are comparable to functional outcomes post primary TKA. The results support the use of HTO for young, male and less co-morbid patients.

Intrapulmonary and Systemic Pharmacokinetics of Colistin Following Nebulization of Low-Dose Colistimethate Sodium in Patients with Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii.

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration-time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.

Distribution of Pt single atom coordination environments on anatase TiO2 supports controls reactivity.

Single-atom catalysts (SACs) offer efficient metal utilization and distinct reactivity compared to supported metal nanoparticles. Structure-function relationships for SACs often assume that active sites have uniform coordination environments at particular binding sites on support surfaces. Here, we investigate the distribution of coordination environments of Pt SAs dispersed on shape-controlled anatase TiO2 supports specifically exposing (001) and (101) surfaces. Pt SAs on (101) are found on the surface, consistent with existing structural models, whereas those on (001) are beneath the surface after calcination. Pt SAs under (001) surfaces exhibit lower reactivity for CO oxidation than those on (101) surfaces due to their limited accessibility to gas phase species. Pt SAs deposited on commercial-TiO2 are found both at the surface and in the bulk, posing challenges to structure-function relationship development. This study highlights heterogeneity in SA coordination environments on oxide supports, emphasizing a previously overlooked consideration in the design of SACs.

Application of surface-guided radiation therapy in prostate cancer: comparative analysis of differences with skin marking-guided patient setup.

PURPOSE: Surface-guided radiation therapy is an image-guided method using optical surface imaging that has recently been adopted for patient setup and motion monitoring during treatment. We aimed to determine whether the surface guide setup is accurate and efficient compared to the skin-marking guide in prostate cancer treatment. MATERIALS AND METHODS: The skin-marking setup was performed, and vertical, longitudinal, and lateral couch values (labeled as "M") were recorded. Subsequently, the surface-guided setup was conducted, and couch values (labeled as "S") were recorded. After performing cone-beam computed tomography (CBCT), the final couch values was recorded (labeled as "C"), and the shift value was calculated (labeled as "Gap (M-S)," "Gap (M-C)," "Gap (S-C)") and then compared. Additionally, the setup times for the skin marking and surface guides were also compared. RESULTS: One hundred and twenty-five patients were analyzed, totaling 2,735 treatment fractions. Gap (M-S) showed minimal differences in the vertical, longitudinal, and lateral averages (-0.03 cm, 0.07 cm, and 0.06 cm, respectively). Gap (M-C) and Gap (S-C) exhibited a mean difference of 0.04 cm (p = 0.03) in the vertical direction, a mean difference of 0.35 cm (p = 0.52) in the longitudinal direction, and a mean difference of 0.11 cm (p = 0.91) in the lateral direction. There was no correlation between shift values and patient characteristics. The average setup time of the skin-marking guide was 6.72 minutes, and 7.53 minutes for the surface guide. CONCLUSION: There was no statistically significant difference between the surface and skin-marking guides regarding final CBCT shift values and no correlation between translational shift values and patient characteristics. We also observed minimal difference in setup time between the two methods. Therefore, the surface guide can be considered an accurate and time-efficient alternative to skin-marking guides.

Outcome of dose-escalated intensity-modulated radiotherapy for limited disease small cell lung cancer.

PURPOSE: An optimal once-daily radiotherapy (RT) regimen is under investigation for definitive concurrent chemoradiotherapy (CCRT) in limited disease small cell lung cancer (LD-SCLC). We compared the efficacy and safety of dose escalation with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Between January 2016 and March 2021, patients treated with definitive CCRT for LD-SCLC with IMRT were retrospectively reviewed. Patients who received a total dose <50 Gy or those with a history of thoracic RT or surgery were excluded. The patients were divided into two groups (standard and dose-escalated) based on the total biologically effective dose (BED, α/ß = 10) of 70 Gy. The chemotherapeutic regimen comprised four cycles of etoposide and cisplatin. RESULTS: One hundred and twenty-two patients were analyzed and the median follow-up was 27.8 months (range, 4.4 to 76.9 months). The median age of the patients was 63 years (range, 35 to 78 years) and the majority had a history of smoking (86.0%). The 1- and 3-year overall survival rates of the escalated dose group were significantly higher than those of the standard group (93.5% and 50.5% vs. 76.7% and 33.3%, respectively; p = 0.008), as were the 1- and 3-year freedom from in-field failure rates (91.4% and 66.5% vs. 73.8% and 46.9%, respectively; p = 0.018). The incidence of grade 2 or higher acute and late pneumonitis was not significantly different between the two groups (p = 0.062, 0.185). CONCLUSION: Dose-escalated once-daily CCRT with IMRT led to improved locoregional control and survival, with no increase in toxicity.

How Pt Influences H2 Reactions on High Surface-Area Pt/CeO2 Powder Catalyst Surfaces.

The addition of platinum-group metals (PGMs, e.g., Pt) to CeO2 is used in heterogeneous catalysis to promote the rate of redox surface reactions. Well-defined model system studies have shown that PGMs facilitate H2 dissociation, H-spillover onto CeO2 surfaces, and CeO2 surface reduction. However, it remains unclear how the heterogeneous structures and interfaces that exist on powder catalysts influence the mechanistic picture of PGM-promoted H2 reactions on CeO2 surfaces developed from model system studies. Here, controlled catalyst synthesis, temperature-programmed reduction (TPR), in situ infrared spectroscopy (IR), and in situ electron energy loss spectroscopy (EELS) were used to interrogate the mechanisms of how Pt nanoclusters and single atoms influence H2 reactions on high-surface area Pt/CeO2 powder catalysts. TPR showed that Pt promotes H2 consumption rates on Pt/CeO2 even when Pt exists on a small fraction of CeO2 particles, suggesting that H-spillover proceeds far from Pt-CeO2 interfaces and across CeO2-CeO2 particle interfaces. IR and EELS measurements provided evidence that Pt changes the mechanism of H2 activation and the rate limiting step for Ce3+, oxygen vacancy, and water formation as compared to pure CeO2. As a result, higher-saturation surface hydroxyl coverages can be achieved on Pt/CeO2 compared to pure CeO2. Further, Ce3+ formed by spillover-H from Pt is heterogeneously distributed and localized at and around interparticle CeO2-CeO2 boundaries, while activated H2 on pure CeO2 results in homogeneously distributed Ce3+. Ce3+ localization at and around CeO2-CeO2 boundaries for Pt/CeO2 is accompanied by surface reconstruction that enables faster rates of H2 consumption. This study reconciles the materials gap between model structures and powder catalysts for H2 reactions with Pt/CeO2 and highlights how the spatial heterogeneity of powder catalysts dictates the influence of Pt on H2 reactions at CeO2 surfaces.

Current status and trends of pulmonary rehabilitation in South Korea: National level data analysis using Health Insurance Review and Assessment Service (HIRA) database from 2016 to 2018.

In South Korea, there are few studies to understand the current status of pulmonary rehabilitation in clinical practice and develop it. This study aimed to assess the current status and annual changes in the number and pattern of prescriptions for pulmonary rehabilitation before and after its insurance coverage. The trends of pulmonary rehabilitation before and after its insurance coverage commencement were evaluated using the data of 24,380 patients during the 3-year period from 2016 to 2018 that were archived by the National Health Information Database of the Health Insurance Review and Assessment Service in South Korea. The annual total number of patients who received pulmonary rehabilitation was stratified by the type of prescription, sex, age, type of insurance, medical institution, and region. In addition, the frequencies of pulmonary rehabilitation for various diagnoses were investigated using the major codes of the Korean Standard Classification of Disease. The patients who received pulmonary rehabilitation increased by approximately 2 times from 5936 in 2016 (before insurance coverage) to 10,474 in 2019. Before 2017, most patients underwent simple pulmonary rehabilitation coded as MM290. However, since the insurance coverage of rehabilitation exercise for pulmonary disease (MM440), the proportions of patients receiving them increased. Men underwent pulmonary rehabilitation more often than women, and >70% of the patients were aged >60 years. Most patients received pulmonary rehabilitation at tertiary hospitals in Seoul. In 2016, pulmonary rehabilitation was prescribed more frequently for cerebral infarction; after 2017, it was prescribed more frequently for lung cancer. This study summarized the current status and trends of pulmonary rehabilitation in South Korea before and after National Health Insurance Service coverage, which commenced on January 1, 2017. A significant increase in the number of pulmonary rehabilitations was confirmed after the insurance coverage.

A Rare Case of Well-Differentiated Parapharyngeal Liposarcoma.

Parapharyngeal liposarcoma is a rare malignant tumor, the pathogenesis of which is uncertain. Parapharyngeal liposarcoma often causes nonspecific clinical features, including dysphagia, globus sensation, and/or respiratory disturbances. The parapharyngeal space is a rare location for head and neck liposarcoma, and these lesions may therefore be confused with a variety of other tumors that can originate in this area. Here, we report a case of liposarcoma originating from the prestyloid parapharyngeal space and discuss the possible differential diagnosis on radiographic findings.

Quantitative measure of concrete fragment using ANN to consider uncertainties under impact loading.

In this study, numerical analysis was performed to predict amount of fragments and travel distance after collision of a concrete median barrier with a truck under impact loading using Smooth Particle Hydrodynamics (SPH). The obtained results of the SPH analysis showed that amount of fragments and the travel distance can be changed depending on different velocity-to-mass ratios under same local impact energy. Using the results of the SPH analysis, artificial neural network (ANN) was constructed to consider the uncertainties for the prediction of amount of fragments and travel distance of concrete after collision. In addition, the results of the ANN were compared with the results of multiple linear regression analysis (MRA). The ANN results showed better coefficient of determination (R2) than the MRA results. Therefore, the ANN showed improvement than the MRA results in terms of the uncertainties of the prediction of amount of fragments and travel distance. Using the constructed ANN, data augmentation was conducted from a limited number of analysis data using a statistical distribution method. Finally, the fragility curves of the concrete median barrier were suggested to estimate the probability of exceed specific amount of fragments and travel distance under same impact energy.

Prediction of Concrete Fragments Amount and Travel Distance under Impact Loading Using Deep Neural Network and Gradient Boosting Method.

In the present study, the amount of fragments generated and their travel distances due to vehicle collision with concrete median barrier (CMB) was analyzed and predicted. In this regard, machine learning was applied to the results of numerical analysis, which were developed by comparing with field test. The numerical model was developed using smoothed particle hydrodynamics (SPH). SPH is a mesh-free method that can be used to predict the amount of fragments and their travel distances from concrete structures under impact loading. In addition, deep neural network (DNN) and gradient boosting machine (GBM) were also employed as machine learning methods. In this study, the results of DNN, GBM, and numerical analysis were then compared with the conducted field test. Such comparisons revealed that numerical analysis generated lower error than both DNN and GBM. When prediction results of both the amount of fragments and their travel distances were considered, the result of DNN showed smaller errors than that of GBM. Therefore, in studies where machine learning is used to predict the amount of fragments and their travel distances, careful selection of an appropriate method from the various available machine learning methods such as DNN, GBM, and random forest is absolutely important.

Maternal and paternal effects on hyperuricaemia: a cross-sectional study from the seventh Korean National Health and Nutrition Examination Survey.

OBJECTIVE: As the heritability of hyperuricaemia remains largely unexplained, we analysed the association between parental and offspring hyperuricaemia at the phenotype level. METHODS: This cross-sectional study included data on 2373 offspring and both-parent pairs from the seventh Korean National Health and Nutrition Examination Survey. Logistic regression and generalised estimating equation analysis were used to evaluate the association between offspring and parental hyperuricaemia adjusting for metabolic risk factors and alcohol intake. RESULTS: Both maternal and paternal hyperuricaemia were associated with offspring hyperuricaemia among teenagers, but from the age of 20 years, a strong association was observed between offspring and paternal, rather than, maternal hyperuricaemia, and this could not be explained by metabolic risk factors such as obesity. However, there was a positive interaction between offspring alcohol intake and parental hyperuricaemia, and there was a stronger association between terciles of offspring alcohol intake and hyperuricaemia in the presence of parental hyperuricaemia: T1 (reference), T2 odds ratio (OR) 1.1 (0.3-4.6), and T3 OR 3.3 (1.4-7.9) (P for trend .017) vs. T1 (reference), T2 OR 0.7 (0.3-1.9), and T3 OR 1.1 (0.6-2.2) (P for trend .974). CONCLUSION: These results suggest a gene-environment interaction, especially with respect to alcohol intake for hyperuricaemia in Korean adults.

Uncertainty Relation for Errors Focusing on General POVM Measurements with an Example of Two-State Quantum Systems.

A novel uncertainty relation for errors of general quantum measurement is presented. The new relation, which is presented in geometric terms for maps representing measurement, is completely operational and can be related directly to tangible measurement outcomes. The relation violates the naïve bound ℏ/2 for the position-momentum measurement, whilst nevertheless respecting Heisenberg's philosophy of the uncertainty principle. The standard Kennard-Robertson uncertainty relation for state preparations expressed by standard deviations arises as a corollary to its special non-informative case. For the measurement on two-state quantum systems, the relation is found to offer virtually the tightest bound possible; the equality of the relation holds for the measurement performed over every pure state. The Ozawa relation for errors of quantum measurements will also be examined in this regard. In this paper, the Kolmogorovian measure-theoretic formalism of probability-which allows for the representation of quantum measurements by positive-operator valued measures (POVMs)-is given special attention, in regard to which some of the measure-theory specific facts are remarked along the exposition as appropriate.

Unilateral pleuroparenchymal fibroelastosis as a rare form of idiopathic interstitial pneumonia: A case report.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by predominantly upper lobe involvement with pleural fibrosis and subjacent parenchymal fibrosis. Recently, there have been increasing reports of PPFE, and PPFE might coexist with other interstitial lung diseases in the lower lobe and upper lobe. However, cases of unilateral PPFE are scarce. CASE SUMMARY: A 75-year-old Korean male presented to our hospital with chronic dry cough and exertional dyspnea. The patient's symptoms started 6 mo previously and had been gradually worsening. At the time of presentation, he felt dyspnea when walking at his own pace. Radiologic findings suggested PPFE, but the lesion was localized in the upper lobe of the right lung. After multidisciplinary discussion, a transbronchial lung biopsy in the right upper lobe revealed collapsed alveoli with parenchymal fibroelastosis, and elastic van Gieson staining demonstrated septal elastosis with intra-alveolar collagenosis, which met the histopathologic criteria of definite PPFE. After multidisciplinary discussion in an experienced interstitial lung disease center, we confirmed the diagnosis of unilateral PPFE. Furthermore, we confirmed the progression of PPFE on radiologic findings during the follow-up period. CONCLUSION: Clinicians should consider PPFE, even in cases with unilateral, predominantly upper lung involvement in interstitial lung disease patients through multidisciplinary discussion.

Oxidative Methane Conversion to Ethane on Highly Oxidized Pd/CeO2 Catalysts Below 400 °C.

Methane upgrading into more valuable chemicals has received much attention. Herein, we report oxidative methane conversion to ethane using gaseous O2 at low temperatures (<400 °C) and atmospheric pressure in a continuous reactor. A highly oxidized Pd deposited on ceria could produce ethane with a productivity as high as 0.84 mmol gcat -1 h-1 . The Pd-O-Pd sites, not Pd-O-Ce, were the active sites for the selective ethane production at low temperatures. Density functional theory calculations confirmed that the Pd-O-Pd site is energetically more advantageous for C-C coupling, whereas Pd-O-Ce promotes CH4 dehydrogenation. The ceria helped Pd maintain a highly oxidic state despite reductive CH4 flow. This work can provide new insight for methane upgrading into C2 species.

A One-Bag Rapid Desensitization Protocol for Paclitaxel Hypersensitivity: A Noninferior Alternative to a Multi-Bag Rapid Desensitization Protocol.

BACKGROUND: Desensitization is used to safely continue treatment with a culprit drug in patients with drug hypersensitivity. Currently, a multi-bag protocol is widely used for rapid desensitization, but performing the desensitization procedure is labor intensive as pharmacists and nurses need to prepare and administer diluted solutions. However, it has not been investigated whether dilution is essential for successful desensitization. OBJECTIVE: To investigate the efficacy and safety of a nondilution, 1-bag protocol in comparison with a conventional multi-bag protocol for desensitization of patients with paclitaxel hypersensitivity. METHODS: Patients who underwent paclitaxel desensitization between 2011 and 2018 were analyzed in this retrospective cohort study. The completion rate, time to completion, and occurrence and severity of breakthrough reaction (BTR) between a 1-bag protocol and a multi-bag protocol were compared. RESULTS: A total of 211 desensitization procedures were performed, of which 207 procedures (98.1%) were completed successfully. The administration time was significantly shorter in the 1-bag protocol group compared with the conventional multi-bag protocol group (266.0 ± 149.3 minutes vs 484.2 ± 178.6 minutes, P < .05) without differences in the completion rate (97.6% vs 98.9%, P = .645), the incidence of BTR (16.1% vs 27.6%, P = .778), and the proportion of severe BTR (2.6% vs 5.7%, P = .134). CONCLUSIONS: A nondilution, 1-bag protocol is noninferior to a multi-bag rapid desensitization protocol and can be a safe and effective option for paclitaxel desensitization.

Experimental and Numerical Investigation of Deformable Concrete Median Barrier.

In South Korea, the number of vehicles is gradually increasing. The number of heavy vehicles in 2010 increased up to 19% in less than five years. Therefore, the chances of heavy vehicle-concrete median barrier (CMB) collision also became higher than in the past; therefore, a need to study a stricter design level for improving the current CMB (CMB-15) under harsher environments arose. Accordingly, in the present study, a new concrete median barrier was designed under a stricter impact severity, SB6(420 kJ), compared to the current design impact severity, SB5-B (270 kJ). In particular, shock absorbing devices to absorb impact energy were applied to the CMB. An empty space allows the dowel bars to deform and absorb collision energy. Therefore, deformable CMB was designed and tested. The key parameters selected in our study were dowel bar and wire-mesh. A series of numerical analyses were conducted to evaluate the proposed new deformable CMB designs with shock absorbers. Finally, the optimal design, CMB-17S, was proposed after several evaluations of the proposed designs and a full-scale field test. It was found that, although the developed model did not accurately predict the impact sequence due to certain differences between the actual truck and the truck model, the permanent deformation after collision could be well predicted. Based on the observations from a full-scale impact test, it was recommended that the top part of the CMB should be strengthened since major volume loss occurred due to local impact, which appeared to be due to punching shear failure.

Clinical implications of discrepant results between genotypic MTBDRplus and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients.

BACKGROUND: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype-phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF). METHODS: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDRplus test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital. RESULTS: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrug-resistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti-TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF. CONCLUSIONS: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy.