Nationwide Treatment Outcomes of Patients With Multidrug/Rifampin-Resistant Tuberculosis in Korea, 2011-2017: A Retrospective Cohort Study (Korean TB-POST).

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.

Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis.

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 ± 0.016, 0.053 ± 0.017, 0.043 ± 0.016, and 0.019 ± 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 ± 0.028 for the HRZE group and 0.154 ± 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483.

Heterogeneous effects of COVID-19 control measures on tuberculosis in South Korea: an analysis of case notification data.

Coronavirus disease (COVID-19) responses such as social distancing practices can decrease health care access and tuberculosis (TB) notification, particularly among individuals aged 60 years or older. Conversely, they can increase TB notification among younger individuals. These results may be attributable to household transmission and the similarity of TB respiratory symptoms to COVID-19.

Evaluating the impact of the nationwide public-private mix (PPM) program for tuberculosis under National Health Insurance in South Korea: A difference in differences analysis.

BACKGROUND: Public-private mix (PPM) programs on tuberculosis (TB) have a critical role in engaging and integrating the private sector into the national TB control efforts in order to meet the End TB Strategy targets. South Korea's PPM program can provide important insights on the long-term impact and policy gaps in the development and expansion of PPM as a nationwide program. METHODS AND FINDINGS: Healthcare is privatized in South Korea, and a majority (80.3% in 2009) of TB patients sought care in the private sector. Since 2009, South Korea has rapidly expanded its PPM program coverage under the National Health Insurance (NHI) scheme as a formal national program with dedicated PPM nurses managing TB patients in both the private and public sectors. Using the difference in differences (DID) analytic framework, we compared relative changes in TB treatment outcomes-treatment success (TS) and loss to follow-up (LTFU)-in the private and public sector between the 2009 and 2014 TB patient cohorts. Propensity score matching (PSM) using the kernel method was done to adjust for imbalances in the covariates between the 2 population cohorts. The 2009 cohort included 6,195 (63.0% male, 37.0% female; mean age: 42.1) and 27,396 (56.1% male, 43.9% female; mean age: 45.7) TB patients in the public and private sectors, respectively. The 2014 cohort included 2,803 (63.2% male, 36.8% female; mean age: 50.1) and 29,988 (56.5% male, 43.5% female; mean age: 54.7) patients. In both the private and public sectors, the proportion of patients with transfer history decreased (public: 23.8% to 21.7% and private: 20.8% to 17.6%), and bacteriological confirmed disease increased (public: 48.9% to 62.3% and private: 48.8% to 58.1%) in 2014 compared to 2009. After expanding nationwide PPM, absolute TS rates improved by 9.10% (87.5% to 93.4%) and by 13.6% (from 70.3% to 83.9%) in the public and private sectors. Relative to the public, the private saw 4.1% (95% confidence interval [CI] 2.9% to 5.3%, p-value < 0.001) and -8.7% (95% CI -9.7% to -7.7%, p-value <0.001) higher rates of improvement in TS and reduction in LTFU. Treatment outcomes did not improve in patients who experienced at least 1 transfer during their TB treatment. Study limitations include non-longitudinal nature of our original dataset, inability to assess the regional disparities, and verify PPM program's impact on TB mortality. CONCLUSIONS: We found that the nationwide scale-up of the PPM program was associated with improvements in TB treatment outcomes in the private sector in South Korea. Centralized financial governance and regulatory mechanisms were integral in facilitating the integration of highly diverse South Korean private sector into the national TB control program and scaling up of the PPM intervention nationwide. However, TB care gaps continued to exist for patients who transferred at least once during their treatment. These programmatic gaps may be improved through reducing administrative hurdles and making programmatic amendments that can help facilitate management TB patients between institutions and healthcare sectors, as well as across administrative regions.

The burden and predictors of latent tuberculosis infection among immigrants in South Korea: a retrospective cross-sectional study.

BACKGROUND: Approximately one-fourth of the global population is latently infected with Mycobacterium tuberculosis. An understanding of the burden of latent tuberculosis infection (LTBI) among immigrants compared with the general Korean population should be the first step in identifying priority groups for LTBI diagnosis and treatment. The study aimed to compute the age-standardized LTBI prevalence and predictors among immigrants with LTBI in South Korea. METHODS: In 2018, the Korea Disease Control and Prevention Agency implemented a pilot LTBI screening project for immigrants using a chest radiography and the QuantiFERON Gold In-Tube assay. A standardized prevalence ratio (SPR) was computed to compare the LTBI burden in immigrants and the general Korean population. RESULTS: During the duration of the project, a total of 8108 immigrants (5134 males and 2974 females) underwent LTBI screening. The SPR of 1.547 (95% confidence interval [CI] 1.468-1.629) in males and 1.261 (95% CI 1.177-1.349) in females were both higher than the Korean reference population. Furthermore, among the immigrants, those aged < 40 years and Korean diaspora visa holders had a higher SPR. CONCLUSION: This study found a higher LTBI prevalence among immigrant population in South Korea compared to that in the general Korean population, and the SPR was higher among those aged < 40 years and the Korean diaspora. The findings can be used as baseline evidence for including immigrants in South Korea in the at-risk group with a priority need for LTBI screening and treatment.

Association of social deprivation and outdoor air pollution with pulmonary tuberculosis in spatiotemporal analysis.

The objective of this study was to identify the association between social deprivation, outdoor air pollution, and tuberculosis (TB) incidence rate or mortality rate. The study sample comprised 25 districts in Seoul, Korea. We used two public data derived from the Community Health Survey and Seoul Statistics. The geographic information system analysis and random effects Poisson regression were applied to explore the association of social deprivation and air pollution with TB incidence and mortality. An 1 ppb increase in sulfur dioxide (SO2) concentration was significantly associated with the risk of TB incidence (risk ratio [RR] = 1.046, 95% confidence interval [CI]: 1.028, 1.065). An 1 unit increase in the deprivation index was significantly related to a6% increase in the mortality of TB (RR = 1.063, 95% CI: 1.031, 1.097). : Our results imply that social deprivation and air pollution may affect the different TB outcomes. Effective policy-making for TB control should reflect the differing outcomes between TB incidence and mortality.

Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the ß' subunit of RNA polymerase.

Rifampicin resistance, a defining attribute of multidrug-resistant tuberculosis, is conferred by mutations in the ß subunit of RNA polymerase. Sequencing of rifampicin-resistant (RIF-R) clinical isolates of Mycobacterium tuberculosis revealed, in addition to RIF-R mutations, enrichment of potential compensatory mutations around the double-psi ß-barrel domain of the ß' subunit comprising the catalytic site and the exit tunnel for newly synthesized RNA. Sequential introduction of the resistance allele followed by the compensatory allele in isogenic Mycobacterium smegmatis showed that these mutations respectively caused and compensated a starvation enhanced growth defect by altering RNA polymerase activity. While specific combinations of resistance and compensatory alleles converged in divergent lineages, other combinations recurred among related isolates suggesting transmission of compensated RIF-R strains. These findings suggest nutrient poor growth conditions impose larger selective pressure on RIF-R organisms that results in the selection of compensatory mutations in a domain involved in catalysis and starvation control of RNA polymerase transcription.

Linezolid for treatment of chronic extensively drug-resistant tuberculosis.

BACKGROUND: Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS: We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS: By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS: Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).

Laparoscopic approach to mucocele of appendiceal mucinous cystadenoma: feasibility and short-term outcomes in 24 consecutive cases.

BACKGROUND: Mucocele of the appendix is an uncommon condition where luminal distention by mucin is usually attributable to a mucinous cystadenoma. From a surgical standpoint, it is critical that the mucin-filled tumor remains intact during resection. Spillage of mucin into peritoneal cavity may otherwise lead to pseudomyxoma peritonei. Although acute appendicitis is managed successfully by laparoscopic appendectomy, the potential for rupture has fueled concerns over laparoscopic resection of appendiceal mucoceles. Our aim was to evaluate feasibility, safety, and short-term outcomes of laparoscopic resection in patients with a mucocele of appendix secondary to mucinous cystadenoma. METHODS: Data collected prospectively at the Department of Surgery from October 2005 to December 2013 were reviewed, selecting all instances of preoperatively identified appendiceal mucoceles, which was confirmed as mucinous cystadenomas by histology after elective laparoscopic surgery. Patient demographics, surgical data (operative procedures and times, intraoperative complications), and short-term postoperative outcomes were analyzed retrospectively. RESULTS: Twenty-four consecutive patients (female 14) were studied. Mean age was 60.0 years (range 42-81 years). Surgical procedures included simple appendectomy (1/24, 4.2 %), partial cecectomy (15/24, 62.5 %), and ileocecal resection (8/24, 33.3 %). Mean operative time was 108.5 min (range 40-205 min). No intraoperative spillage of mucin occurred due to inadvertent rupture of tumor. Resection margins uniformly were negative for tumor. Mean maximal length and diameter of tumors were 7.9 cm (range 3.0-20.0 cm) and 3.2 cm (range 1.0-7.5 cm), respectively. One patient (4.2 %) suffered postoperative morbidity (wound infection). CONCLUSIONS: A laparoscopic approach proved feasible and safe for surgical management of appendiceal mucocele due to mucinous cystadenoma. However, long-term follow-up is warranted for more conclusive support.

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012.

BACKGROUND: Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea. METHODS: New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed. RESULTS: The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ≥3 previous TB episodes, ≥1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ≥35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ≥50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history. CONCLUSIONS: Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00341601.

Beyond reducing direct medical cost: examining health outcomes in tuberculosis through a difference-in-differences analysis of South Korea's out-of-pocket payment exception policy.

Background: Universal health coverage and social protection are major global goals for tuberculosis. This study aimed to investigate the effects of an expanded policy to guarantee out-of-pocket costs on the treatment outcomes of patients with tuberculosis. Methods: By linking the national tuberculosis report and health insurance data and performing covariate-adjusted propensity-score matching, we constructed data on health insurance beneficiaries (treatment group) who benefited from the out-of-pocket payment exemption policy and medical aid beneficiaries as the control group. Using difference-in-differences analysis, we analyzed tuberculosis treatment completion rates and mortality in the treatment and control groups. Results: A total of 41,219 persons (10,305 and 30,914 medical aid and health insurance beneficiaries, respectively) were included in the final analysis (men 59.6%, women 40.4%). Following the implementation of out-of-pocket payment exemption policy, treatment completion rates increased in both the treatment and control groups; however, there was no significant difference between the groups (coefficient, -0.01; standard error, 0.01). After the policy change, the difference in mortality between the groups increased, with mortality decreasing by approximately 3% more in the treatment group compared with in the control group (coefficient: -0.03, standard error, 0.01). Conclusion: There are limitations to improving treatment outcomes for tuberculosis with an out-of-pocket payment exemption policy alone. To improve treatment outcomes for tuberculosis and protect patients from financial distress due to the loss of income during treatment, it is essential to proactively implement complementary social protection policies.

Timing and predictors of death during treatment in patients with multidrug/rifampin-resistant tuberculosis in South Korea.

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.

A Quasi-experimental Study on the Effect of Pre-entry Tuberculosis Screening for Immigrants on Treatment Outcomes in South Korea: A Difference-in-Differences Analysis.

OBJECTIVE: This study ascertains the effects of the pre-entry tuberculosis (TB) screening policy, which was implemented as a strategy for managing TB among immigrants, on the treatment outcomes of immigrants in South Korea. METHODS: This study linked three different datasets from 2013 to 2018, namely (1) Korean National Tuberculosis Surveillance System; (2) National Health Information Database for patients diagnosed with TB with ICD code A15-A19, B90, or U84.3; and (3) Statistics Korea database related to cause of deaths. To identify the effect of the policy, cohorts comprising Korean and immigrant TB patients notified before (January 1, 2013-December 31, 2015) and after (September 1, 2016-December 31, 2018), the implementations of the policy were established. A difference-in-differences (DID) analysis of the treatment success and mortality rates was performed. RESULTS: Data from 100,262 TB patients were included in the analysis (before policy implementation: 1240 immigrants and 65,723 Koreans; after policy implementation: 256 immigrants and 33,043 Koreans). The propensity score matching-DID analysis results showed that the difference in the treatment success rate between immigrants and Koreans decreased significantly, from 16% before to 6% after the policy implementation. The difference in the mortality rate between the two groups decreased from - 3% before to - 1% after the policy implementation; however, this difference was insignificant. CONCLUSION: The treatment outcomes of immigrant TB patients in South Korea improved after the implementation of the pre-entry active TB screening policy. Future immigrant TB policies should consider establishing active patient support strategies and a healthcare collaboration system between countries.

Relationship between metformin use and mortality in tuberculosis patients with diabetes: a nationwide cohort study.

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). CONCLUSION: 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.

Association of MUC6-minisatellite variants with susceptibility to rectal carcinoma.

A secreted MUC6 mucin is reported to be expressed highly in the stomach and gall bladder. In previous our study, the five minisatellites were identified and a significant association between MUC6-MS5 alleles and gastric cancer was reported. Because of aberrant MUC6 expression is often found in gastrointestinal diseases, we evaluated a relationship between MUC6-MS5 and susceptibility to colorectal cancers. Case-control study was performed with 1,103 cancer-free controls and 414 rectal cancer cases. A significant association (OR = 2.70) between short rare MUC6-MS5 alleles (7, 9 repeats) and the occurrence of cancer was observed in rectal cancer [95 % confidence interval (CI), 1.12-6.54; p = 0.022]. Furthermore, a comparison by gender showed the differences in the association ratios between rectal cancer and short rare MUC6-MS5 alleles: male, 3.97 (CI: 1.36-11.5; p = 0.006) versus female 0.91 (CI: 0.18-4.75; p = 0.913). We also examined the association according to lymphovascular invasion (LVI). The frequency of LVI positive rectal cancer was increased in short rare allele cases than in the total rectal cases: 16.2 % versus 42.9 %. Therefore, we suggest that the short rare MUC6-MS5 alleles may be related to cancer development in male and these cancer cases may be related the bad prognosis.

Gender differences in tuberculosis patients with comorbidity: A cross-sectional study using national surveillance data and national health insurance claims data in South Korea.

The coexistence of tuberculosis and other chronic diseases complicates disease management. Particularly, the lack of information on the difference in the prevalence of chronic diseases in tuberculosis based on age and gender can hinder the establishment of appropriate public health strategies. This study aimed to identify age- and gender-based differences in the prevalence of chronic diseases as comorbidities in patients with tuberculosis. An anonymized data source was established by linking the national health insurance claims data to the Korean national tuberculosis surveillance data from 2014 to 2018. The prevalence of chronic diseases was stratified by gender and age (age groups: ≤64, 65-74, and ≥75 years), and the differences in the prevalence of chronic diseases were analyzed by multinomial logistic regression and classified using the Charlson Comorbidity Index. A total of 148,055 patients with tuberculosis (61,199 women and 86,856 men) were included in this study. Among the patients aged ≥65 years, 48.2% were female and 38.1% were male. In this age group, the probability of chronic disease comorbidity was higher in female patients than in male patients. The prevalence of congestive heart failure and dementia as comorbidities in patients with tuberculosis increased more drastically with age in women than in men. Thus, the present study confirmed gender and age differences in the distribution of comorbidities among patients with tuberculosis. A more comprehensive gender-responsive approach for patients with tuberculosis and chronic diseases is required to alleviate the double burden of infectious diseases and non-communicable diseases in an aging society.

Unequal burdens of COVID-19 infection: a nationwide cohort study of COVID-19-related health inequalities in Korea.

OBJECTIVES: While the Korean government's response to the coronavirus disease 2019 (COVID-19) pandemic is considered effective given the relatively low mortality rate, issues of inequality have been insufficiently addressed. This study explored COVID-19-related health inequalities in Korea. METHODS: Age standardization for various health inequality indices was derived using data from the Korean National Health Insurance Service, the Korea Disease Control and Prevention Agency, and the Microdata Integrated Service of Statistics Korea. The slope index of inequality (SII) and relative index of inequality (RII) were calculated for socioeconomic variables, while absolute difference (AD) and relative difference (RD) were used for gender and disability inequalities. RESULTS: We observed a number of COVID-19-related health outcome inequalities. Gender inequality was particularly noticeable in infection rates, with the rate of women 1.16 times higher than that of men. In contrast, socioeconomic inequality was evident in vaccination rates, with a 4.5-fold (SII, -4.519; 95% confidence interval, -7.403 to -1.634) difference between the highest and lowest household income groups. Regarding clinical progression post-infection, consistent findings indicated higher risk for men (RD for hospitalization, 0.90; severe cases, 0.54; and fatality, 0.65), individuals with disabilities (RD for hospitalization, 2.27; severe cases, 2.29; and fatality, 2.37), and those from lower socioeconomic groups (SII for hospitalization, 1.778; severe cases, 0.089; and fatality, 0.451). CONCLUSIONS: While the infection risk was nearly ubiquitous, not everyone faced the same level of risk post-infection. To prevent further health inequalities, it is crucial to develop a thoughtful policy acknowledging individual health conditions and resources.

Real-world impact of the fixed-dose combination on improving treatment outcomes of drug-susceptible tuberculosis: a comparative study using multiyear national tuberculosis patient data.

BACKGROUND: The fixed-dose combination (FDC) for first-line antituberculosis (TB) treatment has long been a standard practice worldwide; however, there is limited evidence on whether the use of FDC improves long-term treatment outcomes in the real-world setting. METHODS: We identified 32 239 newly diagnosed patients with drug-susceptible (DS) TB in 2015 and 2016 who had been prescribed FDC or non-FDC TB treatment from a multiyear (2013-2018) national TB cohort database that linked the Korean National Tuberculosis Surveillance System, the National Health Insurance Database and the Health Insurance Review and Assessment Service database. Inverse probability of treatment weighting (IPTW) with a propensity score was used to control for differences in patient characteristics between 5926 patients with TB treated with FDC and 26 313 patients with non-FDC. Multivariable logistic regression analyses were performed to assess for the factors influencing treatment outcomes between the two groups. RESULTS: After IPTW, new patients with DS-TB treated with FDC had higher treatment completion rate (83.9% vs 78.9%, p<0.01) and lower death rates (8.2% vs 9.8%, p<0.01) with similar TB recurrence rate (2.3% vs 2.4%) compared with those treated with non-FDC. In multivariable analyses, FDC use had higher odds treatment completion (adjusted OR 1.45; 95% CI 1.34 to 1.56). Patients with TB with younger age (relative to 70+ age) and higher income level had higher odds for treatment completion. Use of FDC did not influence TB recurrence after treatment completion (adjusted HR 0.94; 95% CI 0.77 to 1.16). The acquired drug resistance rate was similar between the two groups (drug-resistant TB in FDC 4.7% vs non-FDC 5.3%; p=0.80). CONCLUSION: In Korea, prescription of FDC to treat newly diagnosed patients with DS TB improved patient's treatment completion. Use of FDC did not increase the risks of TB recurrence or development of drug resistance.

Retreatment after loss to follow-up reduces mortality in patients with multidrug/rifampicin-resistant tuberculosis.

Background: This study evaluated the risk factors of long-term mortality in patients with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in South Korea who were lost to follow-up (LTFU). Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases, which included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Post-treatment outcomes of patients who were LTFU were compared with those of patients who achieved treatment success. Results: Of the 7226 MDR/RR-TB cases, 730 (10.1%) were LTFU. During a median follow-up period of 4.2 years, 101 (13.8%) of the LTFU patients died: 25 deaths (3.4%) were TB related and 76 (10.4%) were non-TB related. In the LTFU group, the adjusted hazard ratio (aHR) of all-cause mortality (aHR 2.50, 95% CI 1.99-3.15, p<0.001), TB-related mortality (aHR 5.38, 95% CI 3.19-9.09, p<0.001) and non-TB-related mortality (HR 2.21, 95% CI 1.70-2.87, p<0.001) was significantly higher than that in the treatment success group. Independent risk factors for all-cause mortality in the LTFU group were age >55 years, fluoroquinolone resistance, cancer and no retreatment. In the LTFU patients who did not receive retreatment, the risk of non-TB-related mortality (aHR 5.00, 95% CI 1.53-16.37, p=0.008) and consequent all-cause mortality (aHR 2.18, 95% CI 1.08-4.40, p=0.030) was significantly higher than that of patients who received retreatment. Conclusion: Non-TB-related mortality was the main cause of death and might be reduced by retreatment in LTFU patients with MDR/RR-TB.

Sex differences in the impact of diabetes mellitus on tuberculosis recurrence: a retrospective national cohort study.

OBJECTIVES: Whether diabetes mellitus (DM) increases tuberculosis (TB) recurrence risk is debatable. We determined the effect of DM on TB recurrence. METHODS: This retrospective nationwide cohort study included patients with TB who successfully completed TB treatment during 2011-2017 and were followed up for TB recurrence until August 2020. We performed subdistribution hazard model analyses stratified by sex to assess DM risk related to TB recurrence after successful treatment. RESULTS: Of 199,571 participants who had received successful TB treatment, 47,952 (24%) had DM. There were more men (64.4%), positive acid-fast bacilli smears (35.9%), and positive cultures (49.5%) in the DM group. There were 6208 (3.1%) TB recurrences during 5.1 years of follow-up: 38.9% and 26.6% occurred 1 and 1-2 years after treatment completion, respectively. The recurrence rate was higher in the DM group (3.8%) than in the non-DM group (2.9%, P <0.0001). DM was associated with a higher TB recurrence risk, especially in men (adjusted hazard ratio 1.23, 95% confidence interval 1.15-1.32) but not in women (adjusted hazard ratio 0.96, 95% confidence interval 0.85-1.09). CONCLUSION: The TB recurrence rate after successful treatment was higher in patients with DM than in patients without DM. DM is associated with TB recurrence in men.