Timely Pulmonary Tuberculosis Diagnosis Based on the Epidemiological Disease Spectrum: Population-Based Prospective Cohort Study in the Republic of Korea.

BACKGROUND: Timely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. OBJECTIVE: We aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. METHODS: The Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. RESULTS: Among the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. CONCLUSIONS: Timely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Estimating the prevalence and clinical significance of chronic obstructive pulmonary disease-obstructive sleep apnea overlap in South Korea.

INTRODUCTION: Concurrent obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are referred to as COPD-OSA overlap. We investigated the prevalence and clinical significance of COPD-OSA overlap in the general population of South Korea. METHODS: Data were obtained from the 2019 Korea National Health and Nutrition Examination Survey. Participants ≥40 years of age with complete STOP-Bang questionnaire and spirometry data were included. OSA was presumed in individuals with a STOP-Bang score of ≥3. COPD was determined using forced expiratory volume at 1 s/forced vital capacity <0.7. Participants were classified on the basis of the STOP-Bang score and spirometry findings. Clinical characteristics, comorbidities, and quality of life (using the EuroQoL 5-dimension instrument) were compared between the overlap group and COPD-alone or OSA-alone groups. RESULTS: Among the 3157 participants, 6.9 % demonstrated COPD-OSA overlap. Individuals with OSA alone and COPD alone were 31.8 % and 5.2 %, respectively. The overlap group included more males, ever smokers, and frequent alcohol drinkers than the COPD- or OSA-alone groups. The overlap group had more diagnoses of hypertension, diabetes, and stroke than the COPD-alone group. The risk of anxiety/depression was approximately 2.5 times higher in the overlap group than in the COPD-alone group. COPD-OSA overlap was a significant risk factor for anxiety/depression after adjusting for age, sex, household income, and education levels. CONCLUSION: COPD-OSA overlap is not rare within the general population of South Korea. Patients with overlap showed more comorbidities and higher levels of anxiety/depression than those in the COPD-alone group.

Characteristics of subclinical tuberculosis compared to active symptomatic tuberculosis using nationwide registry cohort in Korea: prospective cohort study.

Objective: The clinical manifestations of tuberculosis (TB) range from asymptomatic to disseminated depending on the microbiological and immunological status, making the diagnosis challenging. To improve our understanding of the disease progression mechanism, we aimed to identify the characteristics of subclinical TB and important predictors of symptom development. Methods: From July 2018 to June 2019, we systemically collected data from the National Surveillance System of South Korea on patients with pulmonary TB, and compared the characteristics of subclinical and active symptomatic TB patients. Results: A total of 4,636 patients with pulmonary TB were included, and the prevalence of subclinical TB was 37.1% (1,720/4,636). In subclinical TB patients, the positivity rates of acid-fast bacilli (AFB) smear and culture were 16.2 and 50.2%, respectively. Subclinical TB patients were younger (55.6 ± 19.2 vs. 60.7 ± 19.5, P < 0.001), had a higher body mass index (21.7 ± 3.1 vs. 21.0 ± 3.5, P < 0.001), less under Medicaid support, and had lower rates of chronic lung disease, AFB smear and culture positivity, and bilateral disease. Regarding the characteristic differences of individual TB-related symptoms, age was positively associated with dyspnoea and general weakness but negatively associated with chest pain, haemoptysis, and weight loss. Male patients were more prone to weight loss. Chronic lung disease was related to symptoms including cough/phlegm, dyspnoea, and haemoptysis, while autoimmune diseases were associated with fever and weight loss. Conclusions: The development of TB-related symptoms was associated with microbiological burden and clinical characteristics including underlying comorbidities, which should be evaluated carefully.

Risk adjustment model for tuberculosis compared to non-tuberculosis mycobacterium or latent tuberculosis infection: Center for Personalized Precision Medicine of Tuberculosis (cPMTb) cohort database.

BACKGROUND: The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. METHODS: Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. RESULTS: Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. CONCLUSIONS: Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. TRIAL REGISTRATION: This study registered ClinicalTrials.gov NO. NCT05280886.

Do patients attempt and succeed in quitting smoking during tuberculosis treatment? A prospective cohort study.

BACKGROUND: Despite a well-known relation between smoking tobacco and the tuberculosis epidemic, the factors associated with smoking cessation in tuberculosis patients are unclear. This study aims to examine the cascade of smoking cessation and the factors associated with persistent smoking among tuberculosis patients. METHODS: We conducted a prospective cohort study enrolling adult patients with pulmonary tuberculosis between 2016 and 2019 in the Republic of Korea. We examined the smoking status at baseline, followed the current smokers, re-examined their smoking status after 6 months of anti-tuberculosis treatment, and identified the factors associated with persistent smoking. RESULTS: Of the 419 enrolled patients, 109 (26.0%) were current smokers at baseline. Of the 79 current smokers who completed the 6-month survey, 24 (30.4%) succeeded in quitting smoking after 6 months of treatment. The adjusted odds ratio for persistent smoking was 6.57 (95% confidence interval [CI], 1.76-27.83) for drinking and 0.15 (95% CI, 0.03-0.68) for diabetes comorbidity. CONCLUSION: Drinking alcohol and diabetes comorbidity were important factors in smoking cessation. Only one third of the tuberculosis patients in our study cohort succeeded in quitting smoking during the 6-month treatment period. More aggressive interventions for smoking cessation should be adopted within the national anti-tuberculosis program.

Risk of loss to follow-up among tuberculosis patients in South Korea: whom should we focus on?

Introduction: In South Korea, public-private mix (PPM) has been a key strategy in national tuberculosis (TB) control program. This study aimed to identify rate of loss to follow-up (LTFU) among TB patients in nationwide PPM institutions and their risk factors. Methods: A nationwide prospective observational study including drug susceptible TB patients diagnosed from the 1st day to the 10th day of every month between July 2018 and December 2020 in PPM institutions was designed. Multivariable survival models in which death and failure were designated as events with competing risk were used to investigate risk factors for LTFU. Results: A total of 14,942 patients were included. Of them, 356 (2.4%) had an LTFU. Risk factors for LTFU were: underweight patients (adjusted hazard ratio (aHR): 1.47, 95% CI: 1.12-1.92), patients living alone (aHR: 1.43, 95% CI: 1.16-1.76), heavy drinkers (aHR: 1.67, 95% CI: 1.16-2.39), those with malignancy (aHR: 1.49, 95% CI: 1.07-2.05), foreigners (aHR: 5.96, 95% CI: 4.51-7.89), and those with previous TB history reported as an unfavorable outcome (aHR: 4.43, 95% CI: 2.77-7.08). Effect of age on LTFU was not significant. Brief interruption of anti-TB treatment (less than two months) in current session was associated with subsequent LTFU [adjusted odds ratio: 13.09 (10.29-16.66)]. Conclusion: Identifying vulnerability of patients such as living alone, being heavy alcoholics, being foreigners or having previous TB history reported as an unfavorable outcome is required. Thorough case management for these vulnerable groups could be feasible with collaboration between public and private sectors.

Effects of underweight and overweight on mortality in patients with pulmonary tuberculosis.

Background: Poor nutrition increases disease severity and mortality in patients with tuberculosis (TB). There are gaps in our understanding of the effects of being underweight or overweight on TB in relation to sex. Methods: We generated a nationwide TB registry database and assessed the effects of body mass index (BMI) on mortality in patients with pulmonary TB. The cause of death was further classified as TB-related or non-TB-related deaths. First, logistic regression analysis was performed to assess the association between BMI (a continuous variable) and mortality, and subgroup analyses of the multivariable logistic regression model were performed separately in male and female patients. Second, we categorized BMI into three groups: underweight, normal weight, and overweight, and assessed the impact of being underweight or overweight on mortality with reference to normal weight. Results: Among 9,721 patients with pulmonary TB, the mean BMI was 21.3 ± 3.4; 1,927 (19.8%) were underweight, and 2,829 (29.1%) were overweight. In multivariable logistic regression analysis, mortality was significantly increased with the decrement of BMI (adjusted odds ratio [aOR] = 0.893, 95% confidence interval [CI] = 0.875-0.911). In subgroup analyses, underweight patients had significantly higher odds of mortality, especially TB-related deaths (aOR = 2.057, 95% CI = 1.546-2.735). The association with mortality and male patients was higher (aOR = 2.078, 95% CI = 1.717-2.514), compared with female patients (aOR = 1.724, 95% CI = 1.332-2.231). Being overweight had a significant protective effect against TB-related death only in females (aOR = 0.500, 95% CI = 0.268-0.934), whereas its effect on non-TB-related death was observed only in males (aOR = 0.739, 95% CI = 0.587-0.930). Conclusion: Being underweight was linked to high mortality, whereas being overweight had beneficial effects in patients with pulmonary TB.

Deaths from tuberculosis: differences between tuberculosis-related and non-tuberculosis-related deaths.

Objective: Tuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide. The first step in developing strategies to reduce TB mortality is to identify the direct causes of death in patients with TB and the risk factors for each cause. Methods: Data on patients with TB systemically collected from the National Surveillance System of South Korea from January 2019 to December 2020 were included in this study. We analyzed the clinical characteristics associated with TB and non-TB-related deaths, including TB-related symptoms, comorbidities, and radiographic and microbiological findings. Results: Of the total of 12,340 patients with TB, 61% were males with a mean age of 61.3 years. During the follow-up period, the overall mortality rate was 10.6%, with TB-related deaths accounting for 21.3% of all TB deaths. The median survival time in the TB-related death group was 22 days. TB-related death was associated with older age, lower body mass index (BMI), dyspnea, fever, general weakness, bilateral radiographic patterns, and acid-fast bacilli (AFB)-positive smears. Non-TB-related deaths were associated with older age, male sex, lower BMI, comorbidities of heart, liver, kidney, and central nervous system (CNS) diseases, CNS TB involvement, the presence of dyspnea, general weakness, and bilateral radiographic patterns. Conclusion: Patients with high-risk TB must be identified through cause-specific mortality analysis, and the mortality rate must be reduced through intensive monitoring of patients with a high TB burden and comorbidities.

Prediction models for respiratory outcomes in patients with COVID-19: integration of quantitative computed tomography parameters, demographics, and laboratory features.

Background: We aimed to develop integrative machine-learning models using quantitative computed tomography (CT) parameters in addition to initial clinical features to predict the respiratory outcomes of coronavirus disease 2019 (COVID-19). Methods: This was a retrospective study involving 387 patients with COVID-19. Demographic, initial laboratory, and quantitative CT findings were used to develop predictive models of respiratory outcomes. High-attenuation area (HAA) (%) and consolidation (%) were defined as quantified percentages of the area with Hounsfield units between -600 and -250 and between -100 and 0, respectively. Respiratory outcomes were defined as the development of pneumonia, hypoxia, or respiratory failure. Multivariable logistic regression and random forest models were developed for each respiratory outcome. The performance of the logistic regression model was evaluated using the area under the receiver operating characteristic curve (AUC). The accuracy of the developed models was validated by 10-fold cross-validation. Results: A total of 195 (50.4%), 85 (22.0%), and 19 (4.9%) patients developed pneumonia, hypoxia, and respiratory failure, respectively. The mean patient age was 57.8 years, and 194 (50.1%) were female. In the multivariable analysis, vaccination status and levels of lactate dehydrogenase, C-reactive protein (CRP), and fibrinogen were independent predictors of pneumonia. The presence of hypertension, levels of lactate dehydrogenase and CRP, HAA (%), and consolidation (%) were selected as independent variables to predict hypoxia. For respiratory failure, the presence of diabetes, levels of aspartate aminotransferase, and CRP, and HAA (%) were selected. The AUCs of the prediction models for pneumonia, hypoxia, and respiratory failure were 0.904, 0.890, and 0.969, respectively. Using the feature selection in the random forest model, HAA (%) was ranked as one of the top 10 features predicting pneumonia and hypoxia and was first place for respiratory failure. The accuracies of the cross-validation of the random forest models using the top 10 features for pneumonia, hypoxia, and respiratory failure were 0.872, 0.878, and 0.945, respectively. Conclusions: Our prediction models that incorporated quantitative CT parameters into clinical and laboratory variables showed good performance with high accuracy.

Differential effects of sex on tuberculosis location and severity across the lifespan.

Disparities exist between sexes regarding tuberculosis (TB) incidence, as well as disease severity and outcome. Using a nationwide TB registry database, we explored the impact of sex and age on extrapulmonary TB (EPTB) among all enrolled patients by (1) calculating the female proportion for every age category according to TB-affected locations, (2) calculating the proportions of EPTB stratified by sex according to age, (3) conducting multivariable analysis to examine the impact of sex and age on EPTB likelihood, and (4) assessing the odds of EPTB for female compared to male as reference in every age category. Further, we explored the impact of sex and age on disease severity among pulmonary TB (PTB) patients. Of all the TB patients, 40.1% were female, with a male-to-female ratio of 1.49. The proportion of females was lowest in their fifties, resembling a U-shape. The male-to-female ratios in PTB and EPTB were 1.67 and 1.03, respectively. Compared to men, women were significantly associated with EPTB in their forties, fifties, and sixties. Female patients with PTB had significantly lower odds of having cavitation and positive smear test results in their fifties. Significant differences were found concerning TB location and severity between sexes, especially during reproductive age.

Clinical phenotypes of chronic cough categorised by cluster analysis.

BACKGROUND: Chronic cough is a heterogeneous disease with various aetiologies that are difficult to determine. Our study aimed to categorise the phenotypes of chronic cough. METHODS: Adult patients with chronic cough were assessed based on the characteristics and severity of their cough using the COugh Assessment Test (COAT) and the Korean version of the Leicester Cough Questionnaire. A cluster analysis was performed using the K-prototype, and the variables to be included were determined using a correlation network. RESULTS: In total, 255 participants were included in the analysis. Based on the correlation network, age, score for each item, and total COAT score were selected for the cluster analysis. Four clusters were identified and characterised as follows: 1) elderly with mild cough, 2) middle-aged with less severe cough, 3) relatively male-predominant youth with severe cough, and 4) female-predominant elderly with severe cough. All clusters had distinct demographic and symptomatic characteristics and underlying causes. CONCLUSIONS: Cluster analysis of age, score for each item, and total COAT score identified 4 distinct phenotypes of chronic cough with significant differences in the aetiologies. Subgrouping patients with chronic cough into homogenous phenotypes could provide a stratified medical approach for individualising diagnostic and therapeutic strategies.

Unilateral diffuse alveolar haemorrhage with microscopic polyangiitis: A case report.

Diffuse alveolar haemorrhage (DAH) is a life-threatening condition caused by widespread damage to the small pulmonary vessels. Common chest imaging findings in patients with DAH show bilateral diffuse airspace opacities. DAH complicating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, including microscopic polyangiitis, should be considered as a differential diagnosis in patients with progressive dyspnea, reduced haemoglobin levels, and alveolar opacities on chest imaging. We report the case of a 78-year-old woman who presented with unilateral DAH, severe dyspnea, and anaemia. DAH was confirmed using bronchoalveolar lavage. Laboratory test results, including ANCA, positive anti-myeloperoxidase antibody, and negative anti-proteinase 3, led to a diagnosis of microscopic polyangiitis. Rituximab and methylprednisolone were administered. The patient's symptoms, laboratory test results, and chest radiography findings improved after the initiation of treatment. This case highlights the importance of prompt recognition of clinical symptoms and signs, including dyspnea and anaemia, for the diagnosis of DAH.

Association of Underlying Comorbidities and Sites of tuberculosis: an analysis using surveillance data.

BACKGROUND: Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site. METHODS: We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB. RESULTS: A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52-4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08-6.99). CONCLUSIONS: We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas.

The cascade of care for latent tuberculosis infection in congregate settings: A national cohort analysis, Korea, 2017-2018.

Background: In 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework. Materials and methods: We undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment. Results: Among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20-34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people "not initiating treatment" (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95-3.86). Nine-month isoniazid monotherapy therapy was associated with "not completing treatment," compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16-1.41). Conclusion: Among participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

Time delays and risk factors in the management of patients with active pulmonary tuberculosis: nationwide cohort study.

Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0-40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639-2.687; p < 0.001] and heavy alcohol intake (adjusted OR 1.505; 95% CI 1.187-1.907; p < 0.001). The median healthcare delay was 5.0 (1.0-14.0) days. A longer healthcare delay was associated with malignancy (adjusted OR 1.351; 95% CI 1.069-1.709; p = 0.012), autoimmune disease (adjusted OR 2.445; 95% CI 1.295-4.617; p = 0.006), and low bacterial burden manifested as an acid-fast bacillus smear-negative and tuberculosis polymerase chain reaction-negative status (adjusted OR 1.316; 95% CI 1.104-1.569; p = 0.002). Active case-finding programmes need to focus on patients with heavy alcoholism or neuropsychiatric diseases. To ensure early PTB detection, healthcare providers must carefully monitor patients with malignancy, autoimmune disease, or a high index of suspicion for PTB.

Hidden loss to follow-up among tuberculosis patients managed by public-private mix institutions in South Korea.

In South Korea, public-private mix (PPM) was launched in 2011. This retrospective cohort study sought to determine the rate of loss to follow-up (LTFU) among drug-susceptible tuberculosis (DS-TB) patients in all nationwide PPM institutions, and the risk factors for LTFU. National notification data for DS-TB patients diagnosed between August 2011 and July 2014 in PPM institutions were analysed. Determination of LTFU included detection of instances where patients were transferred out, but when they did not attend at other TB centres in the following two months. Univariable and multivariable competing risk models were used to determine risk factors for LTFU. 73,046 patients with 78,485 records were enrolled. Nominally, 3426 (4.4%) of records were LTFU. However, after linking the multiple records in each patient, the percentage of LTFU was 12.3% (9004/73,046). Risk factors for LTFU were: being foreign-born (3.13 (95% CI 2.77-3.53)), prior LTFU (2.31 (2.06-2.59)) and greater distance between the patient's home and the TB centre (4.27 (4.03-4.53)). 'Transfer-out' was a risk factor in patients managed by treatment centres close to home (1.65 (1.49-1.83)), but protective for those attending centres further (0.77 (0.66-0.89)) or far-away (0.52 (0.46-0.59)) from home. By considering the complete picture of a patient's interactions with healthcare, we identified a much higher level of LTFU than previously documented. This has implications for how outcomes of treatment are reported and argues for a joined-up national approach for the management and surveillance of TB patients, in nations with similar healthcare systems.

Cluster analysis categorizes five phenotypes of pulmonary tuberculosis.

Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications.