Incidence, Severity, and Mortality of Influenza During 2010-2020 in Korea: A Nationwide Study Based on the Population-Based National Health Insurance Service Database.

BACKGROUND: The epidemiology of influenza is commonly used to understand and establish relevant health policies for emerging respiratory infections, including coronavirus disease 2019 (COVID-19). However, Korea has no confirmed nationwide data on influenza incidence, severity, and mortality rate. METHODS: We conducted a cross-sectional study to obtain epidemic data on influenza at the national level using National Health Insurance claims data during 2010 to 2020. Influenza cases were defined as 90-day timeframe episodes based on all inpatient and outpatient claims data with disease code J09, J10, and J11. Influenza incidence, severity, and mortality rate were calculated, and logistic regressions were performed to assess the associations of demographic characteristics and comorbidity with influenza-related hospitalization, severe illness, and death. RESULTS: There were 0.4-5.9% influenza cases in the population from 2010 to 2020, with 9.7-18.9%, 0.2-0.9%, and 0.03-0.08% hospitalized, used in the intensive care unit, and dead, respectively. Age-standardized incidence and mortality rates were 424.3-6847.4 and 0.2-1.9 per 100,000 population, respectively. While more than half of the influenza cases occurred in populations aged younger than 20 years, deaths in older than 60 years accounted for more than two-thirds of all deaths. CONCLUSION: This study provided the simplest but most important statistics regarding Korean influenza epidemics as a reference. These can be used to understand and manage other new acute respiratory diseases, including COVID-19, and establish influenza-related policies.

Trends in the prescription of benzodiazepines for the elderly in Korea.

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.

Association of cardiovascular health screening with mortality, clinical outcomes, and health care cost: a nationwide cohort study.

OBJECTIVE: To determine whether a cardiovascular disease (CVD) health screening program is associated with CVD-related health conditions, incidence of cardiovascular events, mortality, healthcare utilization, and costs. METHODS: Cohort study of a 3% random sample of all Korea National Health Insurance members 40years of age or older and free of CVD or CVD-related health conditions was conducted. A total 443,337 study participants were followed-up from January 1, 2005 through December 31, 2010. RESULTS: In primary analysis, the hazard ratios for CVD mortality, all-cause mortality, incident composite CVD events, myocardial infarction, cerebral infarction, and cerebral hemorrhage comparing participants who attended a screening exam during 2003-2004 compared to those who did not were 0.58 (95% CI: 0.53-0.63), 0.62 (95% CI: 0.60-0.64), 0.82 (95% CI: 0.78-0.85), 0.84 (95% CI: 0.75-0.93), 0.84 (95% CI: 0.79-0.89), and 0.73 (95% CI: 0.67-0.80), respectively. Screening attenders had higher rates of newly diagnosed hypertension, diabetes mellitus, and dyslipidemia, lower inpatient days of stay and cost, and lower outpatient cost compared to non-attenders. CONCLUSIONS: Participation in CVD health screening was associated with lower rates of CVD, all-cause mortality, and CVD events, higher detection of CVD-related health conditions, and lower healthcare utilization and costs.

Impact of continuity of care on mortality and health care costs: a nationwide cohort study in Korea.

PURPOSE: Continuity of care is considered a core element of high-quality primary care, but its impact on mortality and health care costs is unclear. We aimed to determine the impact of continuity of care on mortality, costs, and health outcomes in patients with newly diagnosed cardiovascular risk factors. METHODS: We conducted a cohort study of a 3% nationwide random sample of Korean National Health Insurance enrollees. A total of 47,433 patients who had received new diagnoses of hypertension, diabetes, hypercholesterolemia, or their complications in 2003 or 2004 were included. We determined standard indices of continuity of care-most frequent provider continuity (MFPC), modified, modified continuity index (MMCI), and continuity of care index (COC)-and evaluated their association with study outcomes over 5 years of follow-up. Outcome measures included overall mortality, cardiovascular mortality, incident cardiovascular events, and health care costs. RESULTS: The multivariable-adjusted hazard ratios (HRs) for all-cause mortality, cardiovascular mortality, incident myocardial infarction, and incident ischemic stroke comparing participants with COC index below the median to those above the median were HR = 1.12 (95% CI, 1.04-1.21), 1.30 (1.13-1.50), 1.57 (1.28-1.95), and 1.44 (1.27-1.63), respectively. Similar findings were obtained for other indices of continuity of care. Lower continuity of care was also associated with increased inpatient and outpatient days and costs. CONCLUSIONS: Lower indices of continuity of care in patients with newly diagnosed hypertension, diabetes, and hypercholesterolemia were associated with higher all-cause and cardiovascular mortality, cardiovascular events, and health care costs. Health care systems should be designed to support long-term trusting relationships between patients and physicians.

Approval status of essential therapeutic drugs for systemic sclerosis versus that of drugs for rheumatoid arthritis.

Objective: Systemic sclerosis, a rare disease characterized by chronic multisystem fibrosis, requires lifelong management, necessitating enough insurance coverage for the patient. Official drug approval is the first step to ensuring that the drug is covered by insurance. In this study, we investigated the approval status of essential therapeutic drugs for systemic sclerosis across eight countries and compared it with that of drugs for rheumatoid arthritis. Methods: The essential therapeutic drug lists for systemic sclerosis and rheumatoid arthritis were taken from the guidelines of the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Official drug approval status for the selected drugs was confirmed by searching representative Internet databases from eight countries: the United States, the United Kingdom, Germany, France, Italy, Switzerland, Japan, and the Republic of Korea. Results: A total of 21 and 16 drugs were selected for systemic sclerosis and rheumatoid arthritis, respectively. The drug approval rates of the 21 drugs for systemic sclerosis varied among countries. Most drugs used to treat pulmonary arterial hypertension, which were developed recently and are expensive, are approved by most countries; however, most older drugs-which are still essential for management of Raynaud's phenomenon, digital ulcers, interstitial lung disease, and skin fibrosis-are not approved by most countries. By contrast, almost all of the 16 drugs used to treat rheumatoid arthritis, whether old or new, are approved by most countries. Conclusion: Approval rates for drugs used to treat systemic sclerosis, a rare disease, are much lower than those for drugs used to treat rheumatoid arthritis. Thus, approval rates of essential therapeutic drugs for systemic sclerosis need to improve, which will benefit patients by increasing the number of drugs covered by insurance.

Health Inequities in Cancer Incidence According to Economic Status and Regions Are Still Existed Even under Universal Health Coverage System in Korea: A Nationwide Population Based Study Using the National Health Insurance Database.

PURPOSE: The purpose of this study is to determine the level of health equity in relation to cancer incidence. MATERIALS AND METHODS: We used the National Health Insurance claims data of the National Health Insurance Service between 2005 and 2022 and annual health insurance and medical aid beneficiaries between 2011 and 2021 to investigate the disparities of cancer incidence. We calculated age-sex standardized cancer incidence rates by cancer and year according to the type of insurance and the trend over time using the annual percentage change. We also compared the hospital type of the first diagnosis by cancer type and year and cancer incidence rates by cancer type and region in 2021 according to the type of insurance. RESULTS: The total cancer incidence increased from 255,971 in 2011 to 325,772 cases in 2021. The absolute difference of total cancer incidence rate between the NHI beneficiaries and the medical aid (MA) recipients increased from 510.1 cases per 100,000 population to 536.9 cases per 100,000 population. The odds ratio of total cancer incidence for the MA recipients increased from 1.79 (95% confidence interval [CI], 1.77 to 1.82) to 1.90 (95% CI, 1.88 to 1.93). Disparities in access to hospitals and regional cancer incidence were profound. CONCLUSION: This study examined health inequities in relation to cancer incidence over the last decade. Cancer incidence was higher in the MA recipients, and the gap was widening. We also found that regional differences in cancer incidence still exist and are getting worse. Investigating these disparities between the NHI beneficiaries and the MA recipients is crucial for implementing of public health policies to reduce health inequities.

An epidemic of cataract surgery in Korea: the effects of private health insurance on the National Health Insurance Service.

OBJECTIVES: In Korea, the National Health Insurance Service (NHIS) covers essential healthcare expenses, including cataract surgery. To address concerns that private health insurance (PHI) might have inflated the need for such procedures, we investigated the extent of the PHI-attributable increase in cataract surgery and its impact on NHIS-reimbursed expenses. METHODS: This retrospective, observational study uses nationwide claims data for cataract surgery from 2016 to 2020. We examined trends in utilization and cost, and we estimated the excess numbers of (1) cataract operations attributable to PHI and (2) types of intraocular lenses used for cataract surgery in 2020. RESULTS: Between 2016 and 2020, a 36.8% increase occurred in the number of cataract operations, with increases of 63.5% and 731.8% in the total healthcare costs reimbursed by NHIS and PHI, respectively. Over a 5-year period, the surgical rate per 100,000 people doubled for patients aged <65 years (from 328 in 2016 to 664 in 2020). Among the 619,771 cases in 2020 of cataract surgery reimbursed by the Korean diagnosis-related group system, more non-NHIS-covered intraocular lenses were used for patients aged <65 years than ≥65 years (68.1 vs. 14.2%). In 2020 alone, an estimated 129,311 excess operations occurred, accounting for an excess cost of US$115 million. CONCLUSIONS: A dramatic increase in the number and cost of cataract operations has occurred over the last 5 years. The PHI-related increase in operations resulted in increased costs to NHIS. Measures to curtail the non-indicated use of cataract surgery should be implemented regarding PHI.

Utility of the REBA MTB-Rifa® assay for rapid detection of rifampicin resistant Mycobacterium tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (TB), including resistance to both rifampicin (RIF) and isoniazid (INH) referred to as multidrug-resistant tuberculosis (MDR-TB), has become an increasing global threat in recent years. Effective management of patients infected with MDR-TB strains requires identifying such patients by performing conventional drug-susceptibility testing (DST) on bacteria isolated from sputum, a process that can take up to 2 months. This delay in diagnosis can result in worsening and continued transmission of MDR-TB. Molecular methods that rely upon nucleic acid amplification of specific alleles known to be associated with resistance to specific drugs have been helpful in shortening the time to detect drug resistant TB. METHODS: We investigated the utility of the REBA MTB-Rifa®, a commercially available line probe assay (LPA) for detecting rifampicin (RIF) resistance in the RIF resistance-determining region (RRDR) of the rpoB gene. Altogether, 492 Mycobacterium tuberculosis (M. tuberculosis) clinical isolates and additional 228 smear- and culture-positive sputum samples with confirmed M. tuberculosis were collected from subjects with suspected MDR-TB in South Korea. The results were compared with conventional phenotypic DST and sequencing of the rpoB gene. RESULTS: A total of 215 of the 492 isolates were resistant to RIF by conventional DST, and of which 92.1% (198/215) were MDR-TB strains. The REBA MTB-Rifa® assay identified RIF resistance in 98.1% (211/215) of these isolates but failed to identify resistance in four phenotypically RIF resistant isolates. These four isolates lacked mutations in the RRDR but three were confirmed to be MDR-TB strains by sequencing. The sensitivity and specificity of this test for clinical isolates was thus 98.1% (211/215) and 100% (277/277), respectively. When applied directly to 228 smear positive sputum samples, the sensitivity and the specificity of REBA MTB-Rifa® assay was 100% (96/96, 132/132), respectively. CONCLUSIONS: These findings support the use of the REBA MTB-Rifa® assay for rapid detection of RIF resistance on clinical isolates and smear positive sputum samples. The results also suggest that RIF resistance is a good surrogate marker of MDR-TB in South Korea and the need to add more probes to other LPAs which can cover newly identified mutations relevant to RIF resistance.

The predictability of claim-data-based comorbidity-adjusted models could be improved by using medication data.

BACKGROUND: Recently, claim-data-based comorbidity-adjusted methods such as the Charlson index and the Elixhauser comorbidity measures have been widely used among researchers. At the same time, there have been an increasing number of attempts to improve the predictability of comorbidity-adjusted models. We tried to improve the predictability of models using the Charlson and Elixhauser indices by using medication data; specifically, we used medication data to estimate omitted comorbidities in the claim data. METHODS: We selected twelve major diseases (other than malignancies) that caused large numbers of in-hospital mortalities during 2008 in hospitals with 700 or more beds in South Korea. Then, we constructed prediction models for in-hospital mortality using the Charlson index and Elixhauser comorbidity measures, respectively. Inferring missed comorbidities using medication data, we built enhanced Charlson and Elixhauser comorbidity-measures-based prediction models, which included comorbidities inferred from medication data. We then compared the c-statistics of each model. RESULTS: 247,712 admission cases were enrolled. 55 generic drugs were used to infer 8 out of 17 Charlson comorbidities, and 106 generic drugs were used to infer 14 out of 31 Elixhauser comorbidities. Before the inclusion of comorbidities inferred from medication data, the c-statistics of models using the Charlson index were 0.633-0.882 and those of the Elixhauser index were 0.699-0.917. After the inclusion of comorbidities inferred from medication data, 9 of 12 models using the Charlson index and all of the models using the Elixhauser comorbidity measures were improved in predictability but, the differences were relatively small. CONCLUSION: Prediction models using Charlson index or Elixhauser comorbidity measures might be improved by including comorbidities inferred from medication data.

The impact of the COVID-19 pandemic in the healthcare utilization in Korea: Analysis of a nationwide survey.

BACKGROUND: COVID-19 has brought changes in daily life and increased the medical burden. This study aims to evaluate the delays in healthcare services and related factors in the general population during the COVID-19 pandemic. METHODS: We took a nationally representative sample and conducted a mobile phone-based survey. The study was conducted anonymously. Of the 3377 subjects who consented to participate, a total of 2097 finished the survey. The primary outcome was respondents' experiences with delayed (1) health screenings, (2) non-urgent medical visits, (3) medical visits for chronic disease, and (4) emergency visits during the COVID-19 pandemic. RESULTS: Of 2097 respondents, females, residents of the Seoul metropolitan area, those with private insurance, those without chronic diseases, smokers, and drinkers had higher risk of delays in health screening and non-urgent medical visits after adjustment. Among chronic disease patients, those who were over 60 years old (adjusted odds ratio 0.36, 95% CI 0.14-0.92) showed lower risk of delayed medical visit. Residents of the Seoul metropolitan area, those with private insurance, smokers, and drinkers were all associated with experiencing delayed health screening and non-urgent medical visits had higher risk of delays in chronic disease visits and emergent medical visits. CONCLUSIONS: Delayed access to healthcare services is associated with poor outcomes and may cause different complications. Efforts are needed to prevent delays in medical use due to infectious diseases such as COVID-19. Considering the possibility of the emergence of infectious diseases, various countermeasures are needed to prevent delays in medical visit.

Mutations in extensively drug-resistant Mycobacterium tuberculosis that do not code for known drug-resistance mechanisms.

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.

Genetic diversity of Mycobacterium tuberculosis isolates from a tertiary care tuberculosis hospital in South Korea.

Tuberculosis (TB) remains an immense public health problem in the Republic of Korea despite a more than fivefold decrease in the prevalence of the disease over the last 3 decades. The rise in drug-resistant TB has compounded the situation. We analyzed 208 clinical isolates of M. tuberculosis from the National Masan Tuberculosis Hospital by spoligotyping, IS6110 restriction fragment length polymorphism (RFLP), and 24-locus-based mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing to assess the diversity and transmission dynamics of the tubercle bacilli in the Republic of Korea. The majority of the isolates (97.1%) belonged to the Beijing genotype. Cluster analysis by MIRU-VNTR yielded a low clustering rate of 22.3%, with most of the clusters comprising isolates with diverse drug resistance patterns. The discriminatory capacity of the typing methods was high for RFLP and MIRU-VNTR (allelic diversity [h] = 0.99) but low for spoligotyping (h = 0.31). Although analysis of 19 MIRU-VNTR loci was needed to achieve maximum discrimination, an informative set of 8 loci (960, 1955, 2163b, 2165, 2996, 3192, 4052, and 4348) (h = 0.98) that was able to differentiate most of the closely related strains was identified. These findings suggest that 24-locus-based MIRU-VNTR typing is a likely suitable alternative to RFLP to differentiate clinical isolates in this setting, which is dominated by M. tuberculosis Beijing strains. Within the study limits, our results also suggest that the problem of drug-resistant TB in the Republic of Korea may be largely due to acquired resistance as opposed to transmission.

Polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in Mycobacterium tuberculosis isolates from South Korean Patients with drug-resistant tuberculosis.

The aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic polypeptide capreomycin are all widely used in second-line therapy for patients who develop multidrug-resistant tuberculosis. We have characterized a set of 106 clinical isolates of Mycobacterium tuberculosis using phenotypic drug susceptibility testing (DST) to determine the extent of resistance to each agent and cross-resistance between agents. These results were compared with polymorphisms in the DNA sequences of ribosome-associated genes previously implicated in resistance and with the clinical outcomes of subjects from whom these isolates were obtained. Thirty-six (34%) of these isolates displayed resistance to one or more of these agents, and the majority of these (20 of 36) showed cross-resistance to one or more agents. Most (33 of 36) of the resistant isolates showed polymorphisms in the 16S ribosome components RpsL and rrs. Three resistant strains (3 of 36) were identified that had no known polymorphisms in ribosomal constituents. For kanamycin and streptomycin, molecular DST significantly outperformed phenotypic DST using the absolute concentration method for predicting 4-month sputum conversion (likelihood ratios of 4.0 and 2.0, respectively) and was equivalent to phenotypic DST using the National Committee for Clinical Laboratory Standards (NCCLS)-approved agar proportion method for estimating MIC (likelihood ratio, 4.0). These results offer insight into mechanisms of resistance and cross-resistance among these agents and suggest that the development of rapid molecular tests to distinguish polymorphisms would significantly enhance clinical utility of this important class of second-line antituberculosis drugs.

Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis.

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.

Evaluation of the diagnostic utility of a whole-blood interferon-gamma assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals.

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% (P < 0.0001) 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 (P < 0.0001). 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.

Variations in the hospital standardized mortality ratios in Korea.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of diabetes and smoking on mortality in tuberculosis.

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.

Alcohol consumption and the risk of type 2 diabetes mellitus: effect modification by hypercholesterolemia: the Third Korea National Health and Nutrition Examination Survey (2005).

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice.

Mycolic acids are attractive diagnostic markers for tuberculosis (TB) infection because they are bacteria-derived, contain information about bacterial species, modulate host-pathogen interactions and are chemically inert. Here, we present a novel approach based on mass spectrometry. Quantification of specific precursor → fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity. We next used this tool in a retrospective case-control study of patients with pulmonary TB with varying disease burdens from South Korea, Vietnam, Uganda and South Africa. MAs were extracted from small volume sputum (200 µl) and analysed without the requirement for derivatization. Infected patients (70, 19 of whom were HIV+) could be separated from controls (40, 20 of whom were HIV+) with a sensitivity and specificity of 94 and 93%, respectively. Furthermore, we quantified MA species in lung tissue of TB-infected mice and demonstrated effective clearance of MA levels following curative rifampicin treatment. Thus, our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers of TB infection.