Search

Despite the continuous implementation of the government’s policy to strengthen NHI coverage, the health insurance coverage rate is still relatively low compared to other OECD countries. The increase in the use of non-essential non-covered medical services is known to be the main cause, and cataract surgery is receiving attention recently as a representative example.A DRG payment system has covered cataract surgery, and NHI has recently covered non-covered ophthalmic examinations. PHI has covered costs for premium lenses and non-covered ophthalmic examinations of cataract surgery. As such, if both NHI and PHI pay for the same medical service, there is a high possibility that the use of non-essential medical services and the cost will increase. Specifically, PHI pays for out-of-pocket costs and expensive multifocal lenses, lowering the patient’s price barrier and increasing the provider’s gross income. In other words, the terms and conditions of PHI that reimbursement for non-covered services without any management mechanism increase the number of surgery using expensive non-covered services according to the rational choice of each stakeholder, thereby affecting the finances of NHI.In order to effectively manage the use of non-essential non-covered medical services, it is necessary to review and manage the structural abnormalities caused by the wrong design of the initial PHI’s terms and conditions.

Objectives Delamanid is a new anti-TB drug, but few data exist on its use outside clinical trials. The purpose of this study was to evaluate the efficacy as well as the safety and tolerability of a delamanid-containing regimen for 24 weeks in the treatment of MDR- and XDR-TB. Methods We performed a retrospective cohort study among patients with MDR/XDR-TB who were treated with a delamanid-containing regimen in seven hospitals in South Korea. Results A total of 32 patients with MDR-TB, of which 6 (18.8%) were XDR-TB, were included and all completed 24 weeks of delamanid treatment. Of 19 patients (59.4%) who had positive culture sputum at the initiation of delamanid treatment, the proportion of culture conversion at 8 weeks was 72.2% (13 of 18) in solid medium and 50.0% (7 of 14) in liquid medium. The proportion of culture conversion at 24 weeks was 94.4% (17 of 18) in solid medium and 92.9% (13 of 14) in liquid medium. The median time to culture conversion was 33 days (range = 5-81) using solid medium and 57 days (range = 8-96) using liquid medium. Of the 32 patients, there was no serious adverse event or death. Three patients developed a transient QTcF of > 500 ms. Conclusions The use of delamanid combined with optimized background regimens has the potential to achieve high culture conversion rates at 24 weeks with an acceptable safety and tolerability profile in patients with MDR/XDR-TB.

Purpose: The aims of this study were to assess the presence of core patient safety practices in Korean hospitals and assess the differences in reporting and learning systems of patient safety, infrastructure, and safe practices by hospital characteristics. Methods: The authors developed a questionna...

The Organization for Economic Cooperation and Development, which has continuously evaluated the performance of healthcare systems, has recently invested much effort into hospital performance measurement. The purpose of this paper is to introduce the hospital performance measurement programs operated by international organizations or at the national level based on the OECD's hospital performance project. Health Insurance Review & Assessment service (HIRA)'s quality assessment was analyzed based on the analytical framework of the OECD's hospital performance project. The hospital performance measurement programs of WHO, Canada, Australia, United States and United Kingdom are briefly explored, in view of the conceptual framework, key performance dimensions and indicators that are currently in use. The OECD suggested seven key dimensions of hospital performance: timeliness, efficiency, continuity, effectiveness and appropriateness, staff orientation, patient orientation and safety. The analysis of the quality assessment program of HIRA, which operates 36 diseases and procedures and 347 indicators, shows that the numbers of indicators are relatively small in the areas of safety, patient centeredness and efficiency. Continuity of care and staff orientation are not fully developed also, but the situations are similar in other countries. In conclusion, hospital performance measurement using stable and comprehensive data should be developed to improve overall system performance, and discussions on a conceptual framework that can lay out directions and key performance domains need to take into place.

The hospital standardized mortality ratio (HSMR) has been widely used because it allows for robust risk adjustment using administrative data and is important for improving the quality of patient care.All inpatients discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were eligible for inclusion. Using the claims data, 29 most responsible diagnosis (MRDx), accounting for 80% of all inpatient deaths among these hospitals, were identified, and inpatients with those MRDx were selected. The final study population included 703 571 inpatients including 27 718 (3.9% of all inpatients) in-hospital deaths. Using logistic regression, risk-adjusted models for predicting in-hospital mortality were created for each MRDx. The HSMR of individual hospitals was calculated for each MRDx using the model coefficients. The models included age, gender, income level, urgency of admission, diagnosis codes, disease-specific risk factors, and comorbidities. The Elixhauser comorbidity index was used to adjust for comorbidities.For 26 out of 29 MRDx, the c-statistics of these mortality prediction models were higher than 0.8 indicating excellent discriminative power. The HSMR greatly varied across hospitals and disease groups. The academic status of the hospital was the only factor significantly associated with the HSMR.We found a large variation in HSMR among hospitals; therefore, efforts to reduce these variations including continuous monitoring and regular disclosure of the HSMR are required.The hospital standardized mortality ratio (HSMR) has been widely used because it allows for robust risk adjustment using administrative data and is important for improving the quality of patient care.All inpatients discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were eligible for inclusion. Using the claims data, 29 most responsible diagnosis (MRDx), accounting for 80% of all inpatient deaths among these hospitals, were identified, and inpatients with those MRDx were selected. The final study population included 703 571 inpatients including 27 718 (3.9% of all inpatients) in-hospital deaths. Using logistic regression, risk-adjusted models for predicting in-hospital mortality were created for each MRDx. The HSMR of individual hospitals was calculated for each MRDx using the model coefficients. The models included age, gender, income level, urgency of admission, diagnosis codes, disease-specific risk factors, and comorbidities. The Elixhauser comorbidity index was used to adjust for comorbidities.For 26 out of 29 MRDx, the c-statistics of these mortality prediction models were higher than 0.8 indicating excellent discriminative power. The HSMR greatly varied across hospitals and disease groups. The academic status of the hospital was the only factor significantly associated with the HSMR.We found a large variation in HSMR among hospitals; therefore, efforts to reduce these variations including continuous monitoring and regular disclosure of the HSMR are required.

The purpose of this study was to evaluate and compare the mental health of patients with retinitis pigmentosa (RP) with that of the general population of Korea.Online surveys were completed by patients registered with the KRPS (Korean Retinitis Pigmentosa Society), an online organization that promotes research on RP and provides advocacy and online and offline support and information for patients with RP. Control population was selected from the fourth round of the KNHANES (Korean National Health and Nutrition Examination Survey). One hundred eighty-seven patients with RP were matched with the control population using the propensity-score method to optimize comparative analysis.Stress was reported in 51.9% of RP patients and 29.4% of controls (p0.001). Depressive mood of at least 2 weeks' duration in the previous year was reported by 34.8 and 17.1% of patients and controls, respectively (p0.001). Suicidal thoughts were reported by 38.5 and 12.9% of patients and controls, respectively (p0.001), although there was no significant difference in the number of suicide attempts between the groups (2.1 vs. 1.6%, p = 0.703). In multivariate analysis, disability rating was significantly associated with stress (adjusted odds ratio, 0.46; 95% confidence interval, 0.24 to 0.88).People with RP had poorer mental health than the general population. Further investigations are warranted on the mental health of RP patients, and appropriate welfare services are needed to decrease the impact of mental illness in this population.

Background This study examined trends in the prescription of benzodiazepines for the elderly (age over 65 years) in Korea, a country with a higher level of spending on pharmaceuticals compared to that in other Organization for Economic Cooperation and Development (OECD) countries, and identified factors related to the inappropriate use of such drugs. Methods We used the National Health Insurance Claims Data (NHICD) for the period 2009–2013, including all reimbursed drug-prescribing information. Following the OECD’s prescribing quality indicators (PQIs), we looked at the prevalence, quantities, durations, and inappropriate (long-term or high-quantity) use of benzodiazepines, some of the most widely prescribed, but potentially inappropriate, drugs for the elderly. We also performed multivariate logistic regression analyses to identify factors related to the inappropriate use of these drugs. Results The annual prevalence of benzodiazepine prescribing for elderly subjects decreased slightly over time but remained high (37.9% in 2009 and 35.1% in 2013). There were also small decreases in the inappropriate long-term use of benzodiazepines over the five years, with a 0.6 decrease in the Defined Daily Dose and a 4.1 per 1,000 decreases in elderly user-days. The proportion of subjects using long-acting benzodiazepines also fell from 263.6 to 220.4 per 1,000 elderly patients. The regression analyses found that the inappropriate long-term use of benzodiazepines in the elderly was significantly related to the patients visiting several institutions and physicians prescribing more than 30 days’ worth of medication. Conclusions The prevalence of prescribing potentially inappropriate drugs, such as benzodiazepines, remains high in Korea. Policy efforts, such as a periodic assessment of prescribing, restricting prescribing days, and more practical guidelines, are needed to improve the quality of prescribing.

Early diagnosis of active tuberculosis (TB) remains an elusive challenge, especially in individuals with disseminated TB and HIV co-infection. Recent studies have shown a promise for the direct detection of pathogen-specific biomarkers such as lipoarabinomannan (LAM) for the diagnosis of TB in HIV-positive individuals. Currently, traditional immunoassay platforms that suffer from poor sensitivity and high non-specific interactions are used for the detection of such biomarkers. In this manuscript, we demonstrate the development of sandwich immunoassays for the direct detection of three TB-specific biomarkers, namely LAM, early secretory antigenic target 6 (ESAT6) and antigen 85 complex (Ag85), using a waveguide-based optical biosensor platform. Combining detection within the evanescent field of a planar optical waveguide with functional surfaces that reduce non-specific interactions allows for the ultra-sensitive and quantitative detection of biomarkers (an order of magnitude enhanced sensitivity, as compared to plate-based ELISA) in complex patient samples (urine, serum) within a short time. We also demonstrate the detection of LAM in urine from a small sample of subjects being treated for TB using this approach with excellent sensitivity and 100% corroboration with disease status. These results suggest that pathogen-specific biomarkers can be applied for the rapid and effective diagnosis of disease. It is likely that detection of a combination of biomarkers offers greater reliability of diagnosis, rather than detection of any single pathogen biomarker. NCT00341601.

Rifampin resistance in Mycobacterium tuberculosis is largely determined by mutations in an 80-bp rifampin resistance determining region (RRDR) of the rpoB gene. We developed a rapid single-well PCR assay to identify RRDR mutations. The assay uses sloppy molecular beacons to probe an asymmetric PCR of the M. tuberculosis RRDR by melting temperature ( T m ) analysis. A three-point T m code is generated which distinguishes wild-type from mutant RRDR DNA sequences in approximately 2 h. The assay was validated on synthetic oligonucleotide targets containing the 44 most common RRDR mutations. It was then tested on a panel of DNA extracted from 589 geographically diverse clinical M. tuberculosis cultures, including isolates with wild-type RRDR sequences and 25 different RRDR mutations. The assay detected 236/236 RRDR mutant sequences as mutant (sensitivity, 100%; 95% confidence interval [CI], 98 to 100%) and 353/353 RRDR wild-type sequences as wild type (specificity, 100%; 95% CI, 98.7 to 100%). The assay identified 222/225 rifampin-resistant isolates as rifampin resistant (sensitivity, 98.7%; 95% CI, 95.8 to 99.6%) and 335/336 rifampin-susceptible isolates as rifampin susceptible (specificity, 99.7%; 95% CI, 95.8 to 99.6%). All mutations were either individually identified or clustered into small mutation groups using the triple T m code. The assay accurately identified mixed (heteroresistant) samples and was shown analytically to detect RRDR mutations when present in at least 40% of the total M. tuberculosis DNA. This was at least as accurate as Sanger DNA sequencing. The assay was easy to use and well suited for high-throughput applications. This new sloppy molecular beacon assay should greatly simplify rifampin resistance testing in clinical laboratories.

Background. Highly lethal outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are increasing. Whole-genome sequencing of KwaZulu-Natal MDR and XDR outbreak strains prevalent in human immunodeficiency virus (HIV)-infected patients by the Broad Institute identified 22 novel mutations which were unique to the XDR genome or shared only by the MDR and XDR genomes and not already known to be associated with drug resistance. Methods. We studied the 12 novel mutations which were not located in highly-repetitive genes to identify mutations that were truly associated with drug resistance or were likely to confer a specific fitness advantage. Results. None of these mutations could be found in a phylogenetically and geographically diverse set of drug-resistant and drug-susceptible Mycobacterium tuberculosis isolates, suggesting that these mutations are unique to the KZN clone. Examination of the 600-basepair region flanking each mutation revealed 26 new mutations. We searched for a convergent evolutionary signal in the new mutations for evidence that they emerged under selective pressure, consistent with increased fitness. However, all but 1 rare mutation were monophyletic, indicating that the mutations were markers of strain phylogeny rather than fitness or drug resistance. Conclusions. Our results suggest that virulent XDR tuberculosis in immunocompromised HIV-infected patients can evolve without generalizable fitness changes or other XDR-specific mutations.

Background The exact role of neutrophils in the pathogenesis of TB is poorly understood. Recent evidence suggests that neutrophils are not simply scavenging phagocytes in Mycobacterium tuberculosis ( Mtb ) infection. Methods Three different types of clinical specimens from patients with active pulmonary TB who underwent lung surgery were examined: sputum, BAL fluid, and cavity contents. Differential cell separation and quantification were performed for intracellular and extracellular bacteria, and bacterial length was measured using microscopy. Results Neutrophils were more abundant than macrophages in sputum (86.6% ± 2.2% vs 8.4% ± 1.3%) and in BAL fluid (78.8% ± 5.8% vs 11.8% ± 4.1%). Inside the cavity, lymphocytes (41.3% ± 11.2%) were the most abundant cell type, followed by neutrophils (38.8% ± 9.4%) and macrophages (19.5% ± 7.5%). More intracellular bacilli were found in neutrophils than macrophages in sputum (67.6% ± 5.6% vs 25.2% ± 6.5%), in BAL fluid (65.1% ± 14.4% vs 28.3% ± 11.6%), and in cavities (61.8% ± 13.3% vs 23.9% ± 9.3%). The lengths of Mtb were shortest in cavities (1.9± 0.1 ± m), followed by in sputum (2.9 ± 0.1 μm) and in BAL fluid (3.6 ± 0.2 μm). Conclusions Our results show that neutrophils are the predominant cell types infected with Mtb in patients with TB and that these intracellular bacteria appear to replicate rapidly. These results are consistent with a role for neutrophils in providing a permissive site for a final burst of active replication of the bacilli prior to transmission.

Purpose. The performance of a computer-based adverse-drug-event (ADE) monitor is evaluated, and the characteristics of ADEs detected and undetected by the monitor are compared. Methods. A retrospective analysis was conducted to identify ADEs using pre-defined ADE alerts that were recognized by a computer-based ADE monitor in a 1300-bed, tertiary care, teaching hospital in Seoul, Korea. A subsequent chart review was conducted by a pharmacist to confirm the ADEs and identify ADEs unrecognized by the monitor. The performance of the monitor was evaluated for its sensitivity and positive predictive value in detecting an ADE. The differences in characteristics of ADEs were compared between computer-recognized ADEs and computer-unrecognized ADEs for severity, causality, preventability, associated clinical manifestations, and types of ADEs. Results. During a one-month period, a total of 598 patients from two intensive care units and five general wards were monitored to identify ADEs. The computer-based ADE monitor identified 148 ADEs, and the chart review identified 39 computer-unrecognized ADEs. The sensitivity of the computer-based ADE monitor was 79% (148 of 187). The computer-recognized ADEs were more severe than computer-unrecognized ADEs, but there were no statistically significant differences in the causality, preventability, and types of ADEs. The positive predictive value of the computer monitor was 21% (148 of 718). Conclusion. The computer-based ADE monitor successfully identified most of the ADEs and almost all of the severe ADEs that occurred in the hospitalized patients. However, the accuracy of the computer-based ADE monitor needs to be improved.

Extensively drug-resistant (XDR) tuberculosis (TB) is a major public health threat in South Korea.We analyzed baseline epidemiological data for 250 patients enrolled in an ongoing prospective observational study of TB at a large tertiary referral hospital in South Korea.Twenty-six subjects with XDR TB were identified; all were patients who had previously received TB therapy. Cumulative previous treatment duration (range, 18-34 months; odds ratio [OR], 5.6; 95% confidence interval [CI], 1.0-59), number of previously received second-line anti-TB drugs (OR, 1.3; 95% CI, 1.1-1.5), and female sex (OR, 3.2; 95% CI, 1.1-8.3) were significantly associated with XDR TB in crude analyses. After controlling for other factors in a multivariable model, cumulative previous treatment duration remained significantly associated with XDR TB (OR, 5.8; 95% CI, 1.0-61). Subjects with XDR TB were more likely to produce culture-positive sputum at 6 months, compared with patients with non-multidrug resistant TB (risk ratio, 13; 95% CI, 5.1-53). Kanamycin resistance was found to be predictive of 6-month culture positivity after adjustment for ofloxacin and streptomycin resistance (risk ratio, 3.9; 95% CI, 1.9-11).XDR TB was found to be associated with the cumulative duration of previous treatment with second-line TB drugs among subjects in a tertiary care TB hospital. Patients with XDR TB were more likely to not respond to therapy, and successful conversion of sputum culture results to negative was correlated with initial susceptibility to both fluoroquinolones and kanamycin but not to streptomycin.

BACKGROUND Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. METHODS Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. RESULTS Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. CONCLUSIONS Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

(See the Editorial Commentary by Daley and Horsburgh on pages 1064–5.) Microbial drug resistance has become a major public health concern worldwide. In the case of tuberculosis, the first global drug resistance survey, published in 1997, reported multidrug-resistant (MDR) tuberculosis (ie, resistant to at least isoniazid and rifampicin) in virtually every participating country [1]. Shortly thereafter, the World Health Organization (WHO) and many other partners launched the DOTS (directly observed treatment, short course)–Plus initiative for the programmatic management of MDR tuberculosis in middle- and low-income countries [2–4] because only a small fraction of MDR tuberculosis cases were diagnosed and treated worldwide [5]. Initially, this initiative focused on the availability, affordability, quality, and control of second-line drugs (SLDs) needed to treat MDR tuberculosis [6]. To the extent that the level of MDR tuberculosis in a country was a barometer for the strength of its basic tuberculosis control program, the partners recognized the risk of generating more highly drug-resistant tuberculosis [4]. Suddenly providing access to relatively obscure and toxic SLDs for treatment of MDR tuberculosis would likely lead to the development of widespread resistance to these same drugs. Indeed, in 2010, WHO estimated that 94 000 of 440 000 (21.4%) MDR tuberculosis cases worldwide may be the consequence of recently acquired resistance [5]. Therefore, WHO and its partners planned to introduce second-line treatment for MDR tuberculosis through an expanding series of pilot and demonstration projects [3, 4, 7]. These projects had to meet specific criteria that were developed to maximize cure rates and minimize the extent to which further drug resistance would develop [7, 8]. These criteria included, as examples, robust political commitment and leadership, a strong basic DOTS program, documented proficiency in phenotypic drug susceptibility testing (DST), strong individualized treatment regimens, 100% direct observation of MDR tuberculosis treatment, assiduous management of drug toxicities, and operational infection control measures. To increase access to SLDs and make them affordable, the Green Light Committee (GLC) established a pooled procurement mechanism consolidating demand into larger, more frequent, more predictable purchases [5, 6]. In turn, major pharmaceutical manufacturers offered 60%–90% price reductions for their brands of quality-assured antituberculosis drugs [6, 7, 9, 10]. Projects procured drugs through this mechanism. To prevent acquired resistance, self-selected programs in middle- and low-income countries applied to the GLC, which evaluated, assisted, approved, and monitored applicants. To evaluate whether programs met the criteria for access to SLDs, the GLC ensured that applicants (1) had strong basic DOTS programs and (2) met the criteria established by WHO's Scientific Panel on MDR Tuberculosis [7, 8]. Under these circumstances, the programs would be granted access to procure high-quality, reduced-price SLDs. From 1 January 2000 to 30 June 2011, the GLC approved 138 projects in 90 countries, representing 131 262 patients with MDR tuberculosis [11]. The GLC Secretariat tracked the procurement, distribution, and utilization of drugs, but there was no built-in mechanism to track acquired SLD resistance. To determine whether this GLC process, in the broad sense, could potentially reduce the frequency of acquired drug resistance, we launched the Preserving Effective TB Treatment Study (PETTS) to quantify the emergence of further resistance to SLD in GLC-approved MDR tuberculosis treatment programs, compared concurrently with non-GLC programs in 2 middle-income and 2 high-income countries.

To investigate the health behaviors of people with retinitis pigmentosa (RP) in the Republic of Korea.An online questionnaire was used to survey members of the Korean Retinitis Pigmentosa Society (KRPS), over 3 months from December 2010 to February 2011. Controls were selected from participants of the 4th Korean National Health and Nutrition Examination Survey and were matched with people with RP using the propensity score method to optimize comparative analysis. A semi-structured interview was also conducted with five members of the KRPS to identify potential reasons for physical inactivity and unhealthy diet and to develop effective interventions.A total of 194 eligible people with RP responded to the online survey, and 187 individuals were matched with the control population by propensity score matching. RP subjects reported a lower rate of current smoking and greater use of preventive healthcare services. However, people with RP were more physically inactive (50.8% vs 27.3%, p 0.001) and consumed more fast food (69.5% vs 58.3%, p = 0.024) than the control population.Physical inactivity and fast food consumption were more frequently reported in people with RP than the general population. Efforts to understand the possible reasons and develop interventions to improve these health behaviors are warranted.

While the protective nature of moderate alcohol consumption against diabetes mellitus is well known, inconsistent findings continue to be reported. The possibility of different mixes of effect modifiers has been raised as a reason for those inconsistent findings. Our study aim was to examine potential effect modifiers that can change the effect of alcohol consumption on type 2 diabetes.From data in the third Korea National Health and Nutrition Examination Survey, 3,982 individuals over the age of 30 years who had not been diagnosed with diabetes were selected for inclusion in the study population. Breslow and Day's test and the Wald test between hypercholesterolemia and alcohol consumption in a multiple logistic regression model were used to assess effect modification.Odds ratios for diabetes stratified by alcohol consumption strata and assessed using Breslow and Day's tests for homogeneity indicated that hypercholesterolemia was not a significant confounding factor (p=0.01). However, the Wald test for interaction terms, which is a conservative method of effect modification, was significant (p=0.03).The results indicate that moderate alcohol consumption is not necessarily protective for type 2 diabetes mellitus, if a person has hypercholesterolemia. People who have hypercholesterolemia should be aware of the risk associated with alcohol consumption, a risk that contrasts with the reported protective effect of moderate alcohol consumption on diabetes.

Background: We have previously reported that TNF-α levels correlate to total mycobacterial burden in tuberculosis (TB) patients. Objective: To characterize the dynamics of cytokine responses in TB patients during chemotherapy to identify potential surrogate markers for effective treatment. Methods: Following induction by culture filtrate proteins in whole blood, production patterns of TNF-α, IL-10, IFN-γ and IL-12 were measured in 23 non-multidrug-resistant (MDR)-TB and 16 MDR-TB patients and in 31 healthy controls. Rates of mycobacterial clearance from the sputum were then measured and compared. Results: Prior to the initiation of chemotherapy, TNF-α and IL-10 levels were significantly higher in TB patients than in healthy controls while IFN-γ and IL-12 levels were similar. During chemotherapy, the levels of all 4 cytokines increased. We evaluated these responses separately in patients that did and did not clear their sputum culture at 2 and 6 months. At 2 months, decreases in both IFN-γ and IL-12 correlated strongly with a successful early response, while after 6 months of therapy, when half (7/14) of MDR-TB patients were still sputum culture positive, downregulation of TNF-α was uniquely correlated with sputum conversion between the groups. Conclusion: Our findings suggest the possibility that the regulation of TNF-α production in whole blood may be a more specific indicator of sputum conversion at 6 months than IFN-γ, IL-12 or IL-10 in MDR-TB patients.

We evaluated the utility of the "QuantiFERON-TB Gold In-Tube" (QuantiFERON) test that uses tuberculosis (TB)-specific antigens for the diagnosis of latent infection in such individuals. We also examined the correlation between the interferon (IFN)-gamma response to these antigens and the exposure risk to TB by evaluating antigen-specific IFN-gamma release in comparison with IFN-gamma release in response to purified protein derivative (PPD) in 3 groups: medical students, nurses in a TB hospital, and TB patients. All nurses and TB patients responded to PPD, whereas 52% (P0.0001) and 79.2% (P = 0.04) responded to QuantiFERON, respectively. In the medical students, only 10.4% responded to QuantiFERON, whereas 85.2% were positive to PPD (P0.0001). There was also a significant correlation between the levels of IFN-gamma production and the duration of employment in the group of nurses at the TB hospital, suggesting ongoing exposure in this high-risk group. Thus, these results demonstrate that Mycobacterium tuberculosis-specific IFN-gamma release assay accurately discriminates low- and high-risk healthy subjects and might therefore be a useful diagnostic tool for the diagnosis of latent infection in Bacille Calmette-Guerin (BCG)-vaccinated individuals.

Background Diabetes mellitus is a risk factor for tuberculosis (TB) disease. There is evidence that diabetes also influences TB severity and treatment outcomes but information is incomplete and some published results have been inconsistent. Methods A longitudinal cohort study was conducted at the National Masan Tuberculosis Hospital in the Republic of Korea. Subjects presenting with a first episode of TB or for retreatment of TB were followed from enrollment through completion of treatment. Demographic, clinical, and microbiological variables were recorded, along with assessment of outcomes. Results were compared in TB patients with and without diabetes or smoking history. Data were adjusted for gender, age, cohort, educational level and alcohol consumption. Results The combined cohorts comprised 657 subjects. Diabetes was present in 25% and was associated with greater radiographic severity and with recurrent or relapsed TB. Diabetes and cigarette smoking independently increased the risk of death in the first 12 months after enrollment. Estimating the combined impact of diabetes and smoking yielded a hazard ratio of 5.78. Only 20% of diabetic subjects were non-smokers; 54% smoked ≥1 pack daily. In this cohort, the impact of diabetes on mortality was greater in patients younger than 50 years, compared to older patients. Conclusions In this cohort of Korean patients, diabetes exacerbated the severity of TB disease. Diabetic subjects who smoked ≥1 pack of cigarettes daily were at particularly high risk of death from TB. Strategies to improve TB outcomes could productively focus resources for patient education and TB prevention on the vulnerable population of younger diabetics, particularly those who also smoke.

Objective: This report is describing the development and implementation process of the knowledge‐based renal dose adjustment system at a university hospital. Method: From the hospital drug formulary which included about 1500 medications, clinical pharmacists selected 243 nephrotoxic medications which require dose adjustment in patients with renal impairment. Through literature review and consultation of clinical pharmacists, nephrologist, and infectious disease specialist, we developed an accordant renal dosing knowledge‐base and used them to build the rules for dosage adjustment alerts and to provide information related to alerts such as patients’age, gender, most recent weight, latest serum creatinine, calculated creatinine clearance, and recommended dosage for renal insufficiency. Status Report: As of August 2006, the renal dosing system which monitored drug prescription and generated real‐time alerting window to help physician to adjust drug doses in patients with renal impairment was implemented and has been operated well since initial implementation. Conclusion: Renal dosing system based upon knowledge‐based renal dosing guideline was successfully developed and implemented into a local clinical practicesetting.

배 경 :결핵의 조기치료와 전염방지를 위해서 신속하고 간편한 결핵진단법의 개발이 요구되고 있는 실정에서 결핵균에 특이한 38-kDa단백을 포함하여 금 콘쥬게이트에 결합된 유전자재조합 항원을 혈청과 반응시켜 항결핵 항체를 발견하도록 고안된 카드형태의 혈청학적 진단기법인 Xeniss Rapid TB kit가 결핵의 진단에 유용하게 이용될 수 있는 지를 알아보고자 하였다.방 법 :188명의 결핵환자(폐결핵 177명, 폐외결핵 11명)와 82명의 접촉자, 그리고 57명의 건강한 성인을 대상으로 하였으며, 연구대상자의 혈청을 이용하여 Xeniss Rapid TB kit의 민감도, 특이도, 양성예측율, 그리고 음성예측율을 조사하였다. 결 과 : 전체적인 민감도는 73.9%, 특이도 81.3%, 양상예측율 84.2%, 그리고 음성예측율은 85.8%였다. 진단시점부터 검사시점간의 시간간격에 따라서는 1개월 이내에서 61.5%로 가장 낮고 점차 증가하여 4-6개월 시점에 94.4%로 가장 높았으며 이후 점차 감소하여 12개월 이상 경과한 시점에서는 67.4%의 양성반응율을 보였다. 페외결핵 환자(90.9%)에서는 폐결핵 환자(72.8%)보다 양성반응율이 높았다. 객담도말양성 (76.2 대 68.4%), 방사선 사진상 중증 (79.3 대 63.3%), 공동성 병소(75.7 대 70.0%), 과거 치료력 (76.3 대 73.3%)이 있는 환자군에서 상대적으로 높은 양성반응율을 보였으며, 당뇨병을 동반한 환자군(69.0 대 74.8%)과 노인환자군(68.l 대 100%)에서는 상대적으로 낮은 양성반응율을 보였다. 건강성인군 7.0%, 환자가족군 17.5%에 비해 병원직원군에서 57.9%의 양성반응율을 보여 활동성 결핵환자와 장기간 지속적으로 접촉한 군에서 높은 양성반응율을 보였다. 결 론 : Xeniss Rapid TB kit는 신속하고 간편하며, 민감도와 특이도가 비교적 높고 특히, 폐외결핵에서는 높은 양성반응율을 보여 폐결핵, 폐외결핵, 그리고 감염자의 진단에 보조적 검사법으로 유용하게 이용될 수 있을 것으로 생각된다. 【Background : The rapid diagnostic tests for tuberculosis are needed to facilitate early treatment of tuberculosis and prevention of Mycobacterium tuberculosis transmission. The Xeniss Rapid TB kit is a rapid, card-based immunochromatographic test for the detection of antibodies directed against M. tuberculosis antigens including antigen 5(38-kDa antigen). The objective of this study was to evaluate the performance of the Xeniss Rapid TB kit for the diagnosis of active tuberculosis with serums from patients, asymptomatic healthy and close contact controls. Methods : 188 patients with active tuberculosis were tested; 177 with pulmonary tuberculosis(18 with combined pleurisy), and 11 with extrapulmonary tuberculosis. The control groups were composed of 82 close contacts and 57 healthy adults. Study subject were drawn from one national tuberculosis hospital for patients and close contacts, and another private hospital for healthy adults in Masan city, Korea. The Xeniss Rapid TB kit(Xeniss Life Science Co., Ltd., Seoul, Korea) was evaluated by using serum samples according to the instructions of the manufacturer by an investigator masked to the clinical and microbiological status of the study subjects. Results : The diagnostic sensitivity of the Xeniss Rapid TB kit was 73.9% in patients and specificities were 73.2% and 93.0% in close contact and healthy adults respectively. The positive predictive value in patients was 84.2% and the negative predictive value in controls was 85.8%. Conclusion : This study shows that the Xeniss Rapid TB test is a simple and fast method to diagnose active TB. The results of the sensitivity and specificites suggest that serodiagnosis using this point of care testing(POCT) device would be valuable and advantageous for screening tuberculosis in the clinical field.】