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Background/Aims@#This study aimed to investigate the timing and predictors of death during treatment among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB) in South Korea. @*Methods@#This was a retrospective cohort study that included MDR/RR-TB cases notified between 2011 and 2017 in South Korea. @*Results@#Among 7,226 MDR/RR-TB cases, 699 (9.7%) died at a median of 167 days (IQR 51–358 d) from the initiation of MDR-TB treatment. The cumulative proportion of all-cause death was 35.5% at 90 days and 52.8% at 180 days from treatment initiation. TB-related deaths occurred at a median of 133 days (IQR 32–366 d), which was significantly earlier than the median of 184 days (IQR 68–356 d) for non-TB-related deaths (p = 0.002). In a multivariate analysis, older age was the factor most strongly associated with death, with those aged ≥ 75 years being 68 times more likely to die (aHR 68.11, 95% CI 21.75–213.26), compared those aged ≤ 24 years. In addition, male sex, comorbidities (cancer, human immunodeficiency virus, and end stage renal disease), the lowest household income class, and TB-specific factors (previous history of TB treatment, smear positivity, and fluoroquinolone resistance) were identified as independent predictors of all-cause death. @*Conclusions@#This nationwide study highlights increased deaths during the intensive phase and identifies high-risk groups including older people and those with comorbidities or socioeconomic vulnerabilities. An integrated and comprehensive strategy is required to reduce mortality in patients with MDR/RR-TB, particularly focusing on the early stages of treatment and target populations.
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Background/Aims@#To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM. @*Methods@#This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI). @*Results@#The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67–0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01). @*Conclusions@#Metformin use in patients with TB–DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.
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Background@#Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. @*Methods@#The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. @*Results@#The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). @*Conclusion@#A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.
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Background@#The treatment outcomes of patients with multidrug/rifampin-resistant (MDR/RR) tuberculosis (TB) are important indicators that reflect the current status of TB management and identify the key challenges encountered by TB control programs in a country. @*Methods@#We retrospectively evaluated the treatment outcomes as well as predictors of unfavorable outcomes in patients with MDR/RR-TB notified from 2011 to 2017, using an integrated TB database. @*Results@#A total of 7,226 patients with MDR/RR-TB were included. The treatment success rate had significantly increased from 63.9% in 2011 to 75.1% in 2017 (P < 0.001). Among unfavorable outcomes, the proportion of patients who failed, were lost to follow up, and were not evaluated had gradually decreased (P< 0.001). In contrast, TB-related death rate was not significantly changed (P= 0.513), while the non-TB related death rate had increased from 3.2% in 2011 to 11.1% in 2017 (P < 0.001). Older age, male sex, immigrants, low household income, previous history of TB treatment, and comorbidities were independent predictors of unfavorable outcomes. Of the 5,308 patients who were successfully treated, recurrence occurred in 241 patients (4.5%) at a median 18.4 months (interquartile range, 9.2–32.4) after completion treatment. @*Conclusion@#The treatment outcomes of patients with MDR/RR-TB has gradually improved but increasing deaths during treatment is an emerging challenge for MDR-TB control in Korea. Targeted and comprehensive care is needed for vulnerable patients such as the elderly, patients with comorbidities, and those with low household incomes.
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We aimed to review the current data composition of the Korean Tuberculosis and Post-Tuberculosis Cohort, which was constructed by linking the Korean Tuberculosis Surveillance System (KNTSS; established and operated by the Korean Disease Control and Prevention Agency since 2000) and the National Health Information Database (NHID; established by the National Health Insurance Service in 2012). The following data were linked: KNTSS data pertaining to patients diagnosed with tuberculosis between 2011 and 2018, NHID data of patients with a history of tuberculosis and related diseases between 2006 and 2018, and data (obtained from the Statistics Korea database) on causes of death. Data from 300 117 tuberculosis patients (177 206 men and 122 911 women) were linked. The rate of treatment success for new cases was highest in 2015 (86.7%), with a gradual decrease thereafter. The treatment success rate for previously treated cases showed an increasing trend until 2014 (79.0%) and decreased thereafter. In total, 53 906 deaths were confirmed among tuberculosis patients included in the cohort. The Korean Tuberculosis and Post-Tuberculosis Cohort can be used to analyze different measurement variables in an integrated manner depending on the data source. Therefore, these cohort data can be used in future epidemiological studies and research on policy-effect analysis, treatment outcome analysis, and health-related behaviors such as treatment discontinuation.
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The Korean government’s strategy to combat coronavirus disease 2019 (COVID-19) has focused on non-pharmaceutical interventions, such as social distancing and wearing masks, along with testing, tracing, and treatment; overall, its performance has been relatively good compared to that of many other countries heavily affected by COVID-19. However, little attention has been paid to health equity in measures to control the COVID-19 pandemic. The study aimed to examine the unequal impacts of COVID-19 across socioeconomic groups and to suggest potential solutions to tackle these inequalities. The pathways linking social determinants and health could be entry points to tackle the unequal consequences of this public health emergency. It is crucial for infectious disease policy to consider social determinants of health including poor housing, precarious working conditions, disrupted healthcare services, and suspension of social services. Moreover, the high levels of uncertainty and complexity inherent in this public health emergency, as well as the health and socioeconomic inequalities caused by the pandemic, underscore the need for good governance other than top-down measures by the government. We emphasize that a people-centered perspective is a key approach during the pandemic era. Mutual trust between the state and civil society, strong accountability of the government, and civic participation are essential components of cooperative disaster governance.
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OBJECTIVES@#Epidemiological evidence of associations between ambient particulate matter (PM) and tuberculosis (TB) risk is accumulating. Two previous studies in Korea found associations between air pollution—especially sulfur dioxide (SO2)—and TB. In this study, we conducted an annual time-series cross-sectional study to assess the effect of PM with an aerodynamic diameter less than 10 μm (PM10) on TB risk in seven major cities of Korea from 2010 to 2016, taking into account time lag and long-term cumulative exposure. @*METHODS@#Age-standardized TB notification rates were derived using the Korea National TB Surveillance System. Annual average PM10 concentrations were obtained from annual Korean air quality reports. We applied a generalized linear mixed model with unconstrained distributed lags of exposure to PM10. We adjusted for potential confounders such as age, health behaviors, and area-level characteristics. @*RESULTS@#Both average annual PM10 concentrations and age-standardized TB notification rates decreased over time. The association between cumulative exposure to PM10 and TB incidence became stronger as a longer exposure duration was considered. An increase of one standard deviation (5.63 μg/m3) in PM10 exposure for six years was associated with a 1.20 (95% confidence interval, 1.17 to 1.22) times higher TB notification rate. The marginal association of exposure duration with the TB notification rate was highest at four and five years prior to TB notification. This association remained consistent even after adjusting it for exposure to SO2. @*CONCLUSIONS@#The findings of this study suggest that cumulative exposure to PM10 may affect TB risk, with a potential lag effect.
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OBJECTIVES@#Epidemiological evidence of associations between ambient particulate matter (PM) and tuberculosis (TB) risk is accumulating. Two previous studies in Korea found associations between air pollution—especially sulfur dioxide (SO2)—and TB. In this study, we conducted an annual time-series cross-sectional study to assess the effect of PM with an aerodynamic diameter less than 10 μm (PM10) on TB risk in seven major cities of Korea from 2010 to 2016, taking into account time lag and long-term cumulative exposure. @*METHODS@#Age-standardized TB notification rates were derived using the Korea National TB Surveillance System. Annual average PM10 concentrations were obtained from annual Korean air quality reports. We applied a generalized linear mixed model with unconstrained distributed lags of exposure to PM10. We adjusted for potential confounders such as age, health behaviors, and area-level characteristics. @*RESULTS@#Both average annual PM10 concentrations and age-standardized TB notification rates decreased over time. The association between cumulative exposure to PM10 and TB incidence became stronger as a longer exposure duration was considered. An increase of one standard deviation (5.63 μg/m3) in PM10 exposure for six years was associated with a 1.20 (95% confidence interval, 1.17 to 1.22) times higher TB notification rate. The marginal association of exposure duration with the TB notification rate was highest at four and five years prior to TB notification. This association remained consistent even after adjusting it for exposure to SO2. @*CONCLUSIONS@#The findings of this study suggest that cumulative exposure to PM10 may affect TB risk, with a potential lag effect.
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BACKGROUND@#The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA).@*METHODS@#The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected.@*CONCLUSION@#NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.
الملخص
BACKGROUND: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA).METHODS: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: Mycobacterium avium complex, M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, or M. kansasii; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected.CONCLUSION: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.
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BACKGROUND@#Tuberculosis (TB) is a major infectious disease in South Korea causing substantial disease burden, particularly in the elderly. This study aimed to identify the case detection rate of mobile TB screening for the elderly conducted in the Jeollanam-do region and to analyze risk factors of active TB.@*METHODS@#We screened the elderly population (≥65 years old) in Jeollanam-do from August to December 2017. Chest radiography was performed for all participants. Participants with TB presumptive signs were asked to submit sputum specimen(s). Sputum smear, culture, and polymerase chain reaction analyses were performed. Cascade analysis, chi-squared tests, and Fisher exact tests were used to evaluate screening performance.@*RESULTS@#In total, 12,402 participants were screened, and 211 (1.7%) were suspected to have active TB; 181 of the suspected patients (85.8%) underwent sputum smear test, and 16 (8.8%) patients were confirmed to have TB. The TB prevalence among the elderly was bacteriologically confirmed to be 129 per 100,000 individuals, which was similar to national TB notification data for the same age groups. The proportion of active TB cases increased with age, and differed based on sex and past TB history. However, TB-related symptoms, comorbidity status, and TB screening history within 12 months were not predictive of active TB.@*CONCLUSION@#This study identified that the prevalence rate was similar to national TB notification data from the same age groups. Periodic, community-based, systematic TB screening among the elderly population is recommended.
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BACKGROUND: Tuberculosis (TB) is a major infectious disease in South Korea causing substantial disease burden, particularly in the elderly. This study aimed to identify the case detection rate of mobile TB screening for the elderly conducted in the Jeollanam-do region and to analyze risk factors of active TB. METHODS: We screened the elderly population (≥65 years old) in Jeollanam-do from August to December 2017. Chest radiography was performed for all participants. Participants with TB presumptive signs were asked to submit sputum specimen(s). Sputum smear, culture, and polymerase chain reaction analyses were performed. Cascade analysis, chi-squared tests, and Fisher exact tests were used to evaluate screening performance. RESULTS: In total, 12,402 participants were screened, and 211 (1.7%) were suspected to have active TB; 181 of the suspected patients (85.8%) underwent sputum smear test, and 16 (8.8%) patients were confirmed to have TB. The TB prevalence among the elderly was bacteriologically confirmed to be 129 per 100,000 individuals, which was similar to national TB notification data for the same age groups. The proportion of active TB cases increased with age, and differed based on sex and past TB history. However, TB-related symptoms, comorbidity status, and TB screening history within 12 months were not predictive of active TB. CONCLUSION: This study identified that the prevalence rate was similar to national TB notification data from the same age groups. Periodic, community-based, systematic TB screening among the elderly population is recommended.
الموضوعات
Aged , Humans , Asian People , Communicable Diseases , Comorbidity , Korea , Mass Screening , Pilot Projects , Polymerase Chain Reaction , Prevalence , Radiography , Risk Factors , Sputum , Thorax , Tuberculosisالملخص
BACKGROUND: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. METHODS: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. RESULTS: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. CONCLUSIONS: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.
الموضوعات
Diagnosis , Extensively Drug-Resistant Tuberculosis , Korea , Linezolid , Methods , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Polymerase Chain Reaction , Tuberculosisالملخص
Much controversy surrounds the issue of whether HIV infection is a risk factor for developing multidrug-resistant tuberculosis (MDR-TB). In this study, we evaluated the prevalence of and risk factors for MDR-TB in HIV-infected patients at the National Medical Center of Korea. We reviewed the medical records of HIV/TB co-infected patients from January 2005 to May 2011; the drug susceptibility profiles were available for 55 patients. Of these, 32.7% had MDR-TB, which was approximately 3.6 times higher than the prevalence among the general population. Additionally, there were more additional AIDS-defining clinical illnesses in the MDR-TB group than in the non-MDR-TB group (27.8% vs 5.4%, P = 0.032). These results suggest that HIV infection and HIV-related immunosuppresion may contribute to the development of MDR-TB.