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.ope

Mortality of patients with chronic obstructive pulmonary disease: a nationwide populationbased cohort study

BACKGROUND/AIMS: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality in the world. There are no population-based studies on longterm mortality in COPD patients in Korea. METHODS: Using the large, population-based, National Health Insurance Service- National Sample Cohort (NHIS-NSC), we identified COPD patients using the International Classification of Disease-Tenth Revision (ICD-10) and prescription details in the NHIS-NSC during 2003 to 2013. We analyzed the survival curves of COPD patients by sex, age, and cause of death. RESULTS: A total of 14,127 individuals older than 40 years were diagnosed with COPD. There were a total of 3,695 deaths (26.2%) in COPD patients during the study period. The 5-year mortality of COPD patients was 25.4% (29.9% in males and 19.1% in females). The mortality rate increased rapidly with age. The most common cause of death in COPD was chronic lower respiratory disease. CONCLUSION: This study described long-term mortality in COPD patients in Korea. Higher mortality was observed in males, and it was closely related to age.ope

Evaluation of the Quality of Care among Hospitalized Adult Patients with Community-Acquired Pneumonia in Korea

Pneumonia is an important cause of morbidity and mortality. Since 2014, the Health Insurance Review and Assessment Service (HIRA) has assessed the overall quality of care among hospitalized adult patients with community-acquired pneumonia (CAP) provided by all medical institutions in Korea. A committee of the Korea Academy of Tuberculosis and Respiratory Diseases developed the hospital inpatient quality measures set for CAP consisting of eight core measures and five monitoring measures. The composite measure score was calculated. The medical records of hospitalized adult patients ages 18 years or more with CAP from October to December 2014 were evaluated. The data of 523 hospitals (42 tertiary hospitals [8.0%], 256 general hospitals [49%], and 225 hospitals [43.0%]) and 15,432 cases (tertiary hospitals, 1,673 cases [10.8%]; general hospitals, 8,803 cases [57.1%]; hospitals, 4,956 cases [32.1%]) were analyzed. We found large variations among institutions in terms of performance of care measures for CAP. For the composite measure score, the mean value was 66.7 (tertiary hospitals, 98.5; general hospitals, 79.2; hospitals, 43.8). Despite significant differences in measure scores between tertiary, general hospitals and hospitals, no significant differences were found in mortality between hospitals. Further studies are needed to determine the care measures appropriate for CAP.ope

Protocol of a Nationwide Observational Study among Patients with Nontuberculous Mycobacterium Pulmonary Disease in South Korea (NTM-KOREA)

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.ope

Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium avium complex pulmonary disease: a systematic review and meta-analysis

BACKGROUND: Macrolide is a key drug in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Macrolide-resistant MAC is gaining importance, but there are little data in clinical characteristics and treatment outcomes of macrolide-resistant MAC-PD (MR-MAC-PD). METHODS: We performed a systematic review and meta-analysis of published studies reporting clinical characteristics and treatment outcomes of patients with MR-MAC-PD. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. RESULTS: Nine studies (seven retrospective and two prospective) comprising 319 patients were identified through a database search. Around 73% were women, and 52% had the fibrocavitary form. Pooled sputum culture conversion rate after combined multiple antibiotics or surgical resection was 21% (95% confidence interval [CI], 14-30%), and the one-year all-cause mortality was 10% (95% CI, 5-20%). There was no significant difference in treatment outcomes between nodular bronchiectatic and fibrocavitary types. CONCLUSIONS: Even combination therapy with fluoroquinolone, aminoglycoside, and surgical resection, the treatment outcomes of MR-MAC-PD were poor. The investigation of new treatment modalities is urgent.ope

Tuberculosis Treatment in Patients with Comorbidities

Tuberculosis is a significant infectious problem in elderly patients with comorbidities in Korea. The age-associated diseases such as malignancy and diabetes mellitus may increase the risk of tuberculosis in this population. The medication treatments of tuberculosis in patients with comorbidities can cause adverse reactions to antituberculosis drugs and inadequate treatment responses. Thus, clinicians must carefully monitor the toxicity of antituberculosis therapy and the efficacy of treatment in patients with comorbidities.ope

Poor correlation between tuberculin skin tests and interferon-γ assays in close contacts of patients with multidrug-resistant tuberculosis

BACKGROUND AND OBJECTIVE: The results of tuberculin skin tests (TST) and QuantiFERON TB-Gold In-Tube (QFT-GIT) assays were compared in close contacts of patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: Close contacts of patients with bacteriologically confirmed MDR-TB (n = 101) were assessed. Most contacts were members of the households of patients, and 79 (78.2%) had received Bacille Calmette-Guerin (BCG) vaccination. Samples from each contact were tested using the TST and the QFT-GIT assay on the same day, and the concordance between these results was assessed using kappa (κ) coefficients. RESULTS: Forty-eight subjects (47.5%) showed positive responses on TST, using a 10-mm induration cut-off, and 54 (53.5%) were positive for the QFT-GIT assay. Of the 48 individuals who were TST positive, 34 (70.8%) were positive for the QFT-GIT assay. Of the 53 subjects who were TST negative, 33 (62.5%) were negative for the QFT-GIT assay. The overall agreement between the two tests (κ coefficient) was 0.33. The κ coefficient was higher in the 22 subjects who had not received BCG vaccination (κ = 0.48) than in the 79 subjects who had received BCG vaccination (κ = 0.29). CONCLUSION: The TST and QFT-GIT assays showed poor correlation in close contacts of patients with MDR-TB, especially those contacts who had received BCG vaccination.ope

Gene-Based Diagnosis of Tuberculosis from Oral Swabs with a New Generation Pathogen Enrichment Technique

A rapid and sensitive diagnosis is crucial for the management of tuberculosis (TB). A simple and label-free approach via homobifunctional imidoesters with a microfluidic platform (SLIM) assay showed a higher sensitivity than the Xpert MTB/RIF assay in the diagnosis of pulmonary TB (PTB). Here, we evaluated the efficacy of the SLIM assay for oral swab samples from cases of suspected PTB. Patients with clinically suspected PTB were prospectively enrolled and oral swab samples were processed using the SLIM assay and the attending physicians were blinded to the results of the SLIM assay. TB cases were defined as those treated with anti-TB chemotherapy for at least 6 months at the discretion of the specialists based on their clinical features and conventional laboratory results, including the Xpert assay. A total of 272 patients (with TB, n = 128 [47.1%]; without TB, n = 144 [52.9%]; mean age, 59.8 years) were enrolled. Overall, the sensitivity of the oral swab-based SLIM assay (65.6%) was higher than that of the sputum-based Xpert assay (43.4%; P = 0.001). Specifically, the SLIM oral swab assay showed a notably higher sensitivity in culture-negative TB cases compared with the Xpert assay (69.0% [95% CI: 49.2 to 84.7%] versus 7.4% [95% CI: 0.9 to 24.3%]; P = 0.001). The specificity of the SLIM and the Xpert assays was 86.1% (95% CI: 79.3 to 91.3%) and 100% (95% CI: 97.2 to 100%), respectively. When only culture-confirmed cases were analyzed, the SLIM oral swab was comparable to sputum Xpert in sensitivity (64.7% versus 54.3%, P = 0.26). The oral swab-based SLIM assay showed a superior sensitivity for TB diagnosis over the sputum-based Xpert assay, especially for culture-negative cases. IMPORTANCE The development of a rapid, accessible, and highly sensitive diagnostic tool is a major challenge in the control and management of tuberculosis. Gene-based diagnostics is recommended for the rapid diagnosis of pulmonary tuberculosis (PTB), but its sensitivity, such as Xpert MTB/RIF assay (Xpert), drops in cases with a low bacterial load. It can only be applied to sputum samples, and it is quite difficult for some patients to produce an adequate amount of sputum. We evaluated the clinical validity of an oral swab-based microfluidic system, i.e., the SLIM assay. The SLIM assay showed a significantly higher sensitivity than the Xpert assay, especially in smear-negative TB cases. This non-sputum-based SLIM assay can be a useful diagnostic test by overcoming the limitations of conventional sputum-based tests in pulmonary TB.ope

Diagnosis and treatment of multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) is a great public health concern worldwide. MDR-TB denotes bacillary resistance to at least isoniazid and rifampicin. Extensively drug-resistant tuberculosis (XDR-TB) is MDR-TB with additional bacillary resistance to any fluoroquinolone and at least one second-line injectable drug. The treatment of MDR-TB requires prolonged administration of a toxic second line anti-tuberculosis drug and generally has poor outcomes. XDR-TB requires more complex treatment and has higher mortality. MDR- and XDR-TB arise because of inadequate or interrupted administration of first-line treatment and can be transmitted in the community. Thus, prevention of the emergence of resistance is the first principle in the management of MDR/XDR-TB. To prevent the emergence of drug resistance and transmission of MDR/XDR-TB, the adequate prescription of an anti-TB drug by a physician and good adherence of patients are essential. In addition, rapid diagnosis of drug resistance using molecular tests such as a line probe assay and Xpert MTB/RIF and the programmatic management of MDR/XDR-TB by designing an effective regimen using available drugs (a newer generation of fluoroquinolone, second-line injectable drugs, second-line oral drugs, and pyrazinamide) based on a guideline are an important strategy for controlling MDR/XDR TB. Despite the long duration of treatment, the treatment success rate of MDR-TB for patients who started treatment in 2009 has been 48% according to the World Health Organization. Thus, to improve the treatment outcomes of MDR/XDR-TB, new drug development is necessary.ope

Prevalence and associated factors of diabetes mellitus among patients with tuberculosis in South Korea from 2011 to 2018: a nationwide cohort study

Objectives: This study aimed to identify the prevalence of diabetes mellitus (DM) among patients with tuberculosis (TB) using a nationwide cohort in South Korea. Design: A retrospective cohort study. Setting: This study used the Korean Tuberculosis and Post-Tuberculosis cohort, which was constructed by linking the Korean National Tuberculosis Surveillance, National Health Information Database (NHID) and Statistics Korea data for the causes of death. Participants: During the study period, all notified patients with TB with at least one claim in the NHID were included. Exclusion criteria were age less than 20 years, drug resistance, initiation of TB treatment before the study period and missing values in covariates. Outcome measures: DM was defined as having at least two claims of the International Classification of Diseases (ICD) code for DM or at least one claim of the ICD code for DM and prescription of any antidiabetic drugs. Newly diagnosed DM (nDM) and previously diagnosed DM (pDM) were defined as DM diagnosed after and before TB diagnosis, respectively. Results: A total of 26.8% (70 119) of patients were diagnosed with DM. The age-standardised prevalence increased as age increased or income decreased. Patients with DM were more likely to be men, older, had the lowest income group, had more acid-fast bacilli smear and culture positivity, had a higher Charlson Comorbidity Index score and had more comorbidities compared with patients without DM. Approximately 12.5% (8823) patients had nDM and 87.4% (61 296) had pDM among those with TB-DM. Conclusions: The prevalence of DM among patients with TB was considerably high in Korea. To achieve the goal of TB control and improve the health outcomes of both TB and DM, integrated screening of TB and DM and care delivery in clinical practice are necessary.ope