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Original Research: Chest Infections |

Optimal Duration of Anti-TB Treatment in Patients With DiabetesAnti-TB Treatment in Patients With Diabetes Mellitus: Nine or Six Months? OPEN ACCESS

Jann-Yuan Wang, PhD; Ming-Chia Lee, MS; Chin-Chung Shu, MD; Chih-Hsin Lee, MD, PhD; Li-Na Lee, PhD; Kun-Mao Chao, PhD; Feng-Yee Chang, PhD
Author and Funding Information

From the Department of Internal Medicine (Dr Wang), the Department of Traumatology (Dr Shu), and the Department of Laboratory Medicine (Dr L. N. Lee), National Taiwan University Hospital, Taipei; the Department of Pharmacy (Mr M. C. Lee), Taipei Tzuchi Hospital, the Buddhist Tzuchi Medical Foundation, New Taipei; the Department of Pulmonary Medicine (Dr C. H. Lee), Wanfang Hospital, Taipei Medical University, Taipei; the Graduate Institute of Biomedical Electronics and Bioinformatics (Dr Chao), National Taiwan University, Taipei; and the Centers for Disease Control (Dr Chang), Taipei, Taiwan.

CORRESPONDENCE TO: Chih-Hsin Lee, MD, PhD, Department of Pulmonary Medicine, Wanfang Hospital, Taipei Medical University, School of Medicine, Taipei Medical University, #111, Section 3, Hsing-Long Rd, Taipei 116, Taiwan; e-mail: chlee.tw@gmail.com


FUNDING/SUPPORT: This study was supported by the National Science Council, Taiwan [Grant NSC 99-2314-B-002-088-MY2] and the Centers for Disease Control, Taiwan [Grant DOH-101-DC-1101].

This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction to noncommercial entities, provided the original work is properly cited. Information for reuse by commercial entities is available online.


Chest. 2015;147(2):520-528. doi:10.1378/chest.14-0918
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BACKGROUND:  Diabetes mellitus (DM) increases the risk of TB recurrence. This study investigated whether 9-month anti-TB treatment is associated with a lower risk of TB recurrence within 2 years after complete treatment than 6-month treatment in patients with DM with an emphasis on the impact of directly observed therapy, short course (DOTs).

METHODS:  Patients with pulmonary but not extrapulmonary TB receiving treatment of 173 to 277 days between 2002 and 2010 were identified from the National Health Insurance Research Database of Taiwan. Patients with DM were then selected and classified into two groups based on anti-TB treatment duration (9 months vs 6 months). Factors predicting 2-year TB recurrence were explored using Cox regression analysis.

RESULTS:  Among 12,688 patients with DM and 43,195 patients without DM, the 2-year TB recurrence rate was 2.20% and 1.38%, respectively (P < .001). Of the patients with DM, recurrence rate decreased from 3.54% to 1.19% after implementation of DOTs (P < .001). A total of 4,506 (35.5%) were classified into 9-month anti-TB treatment group. Although a 9-month anti-TB treatment was associated with a lower recurrence rate (hazard ratio, 0.76 [95% CI, 0.59-0.97]), the benefit disappeared (hazard ratio, 0.69 [95% CI, 0.43-1.11]) under DOTs. Other predictors of recurrence included older age, male sex, malignancy, earlier TB diagnosis year, culture positivity after 2 months of anti-TB treatment, and anti-TB treatment being ≤ 80% consistent with standard regimen.

CONCLUSIONS:  The 2-year TB recurrence rate is higher in a diabetic population in Taiwan and can be reduced by treatment supervision. Extending the anti-TB treatment by 3 months may also decrease the recurrence rate when treatment is not supervised.

Figures in this Article

TB, a global public health threat, is still one of the leading causes of death among infectious diseases, especially in developing countries.1 With the current standard of four combined drugs for 6 months, anti-TB treatment can cure most patients with TB, with a 2-year recurrence rate of 2% to 3%.2,3 The recurrence rate can be further reduced by implementing the policy of directly observed therapy, short course (DOTs).4 Although recurrence does occur, extended treatment of > 6 months is mainly recommended for extrapulmonary TB, drug-resistant TB, or when the regimen is modified because of adverse events, treatment failure, or nonadherence.5

The prevalence of diabetes mellitus (DM) is increasing worldwide, especially in Asia,6 where TB is also highly endemic.1 Numerous studies have presented convincing biologic evidence supporting the causal relationship of DM and impaired host immunity to TB.79 In Taiwan, DM is the most common systemic comorbidity of patients with TB (18.3%-22.1%).10 In a meta-analysis, the relative risk of TB recurrence in patients with DM compared with those without DM was 3.89 (95% CI, 2.43-6.23).11 Given the increased recurrence rate in this special population, it is imperative to know whether increasing the duration of anti-TB treatment will reduce the recurrence rate, especially after implementation of DOTs. However, there is paucity of studies focusing on this issue, perhaps because such studies require large cohorts with long-term follow-up.

As the mandatory universal health insurance program offering comprehensive medical care coverage, the National Health Insurance of Taiwan has covered up to 99% of residents in Taiwan since 1996.12 With a longitudinal follow-up of > 22 million subjects, the National Health Insurance Research Database (NHIRD) provides suitable research material to explore the impact of medical intervention on the outcome of special populations with long-term diseases. During the period since 2006, DOTs has been implemented in Taiwan. Thus, this study was conducted using the NHIRD to investigate the risk factors of TB recurrence in patients with DM, with special emphasis on the impact of anti-TB treatment duration and DOTs.

The institutional review board of National Taiwan University Hospital, Taipei, Taiwan approved this study (NTUH REC: 201112111RIC). As a retrospective study using an encrypted database, the institutional review board waived the need for informed consent.

Case Selection

Patients with pulmonary and without extrapulmonary TB diagnosed from 1996 to 2010 were identified (Fig 1). Those who were diagnosed after January 1, 2002 were selected because comprehensive data on mycobacteriology studies, including acid-fast smear, mycobacterial culture, identification, and drug susceptibility test (DST), were available in NHIRD since then. Given that drug-resistant TB, especially multidrug-resistant TB, was usually treated for > 9 months, only patients who received anti-TB regimen with a duration between 173 and 277 days were selected. Patients were also excluded if they received any non-first-line anti-TB drugs for > 14 days, to avoid inclusion of patients with drug-resistant TB or adverse reaction due to first-line anti-TB drugs. Patients were classified into two groups according to their treatment duration (6 vs 9 months) using 225 days as the cutoff.

Figure Jump LinkFigure 1 –  Flowchart of case selection from the National Health Insurance Research Database of Taiwan. DOTs = directly observed therapy, short course. HREZ = isoniazid, rifamycin, ethambutol, and pyrazinamide.Grahic Jump Location

The primary research outcome was TB recurrence, defined as recurrent episode of active TB within 2 years after completion of anti-TB treatment of the first episode of TB.1 Patients were followed up for 2 years after completion of anti-TB treatment, until TB recurrence, December 31, 2010, or withdrawal of health insurance.

Definition of Active TB

Active pulmonary TB was defined by at least two ambulatory visits or one inpatient record with a compatible diagnosis, plus at least one prescription of three or more anti-TB drugs and prescriptions of at least two anti-TB drugs simultaneously for ≥ 120 days within a period of 180 days (e-Appendix 1).13 Because there was no culture result in the NHIRD, DST ordered after 2 months of anti-TB treatment was used as a proxy for culture positivity after 2 months of anti-TB treatment under the assumption that DST was always done for all positive culture after 2 months of treatment.14 Anti-TB treatment was considered > 80% consistent with standard regimen if isoniazid, rifamycin, ethambutol, and pyrazinamide were given for > 48 days in the first 2 months and isoniazid and rifamycin for > 144 days in the first 6 months of anti-TB treatment. The date of complete treatment was defined as the last date of simultaneous intake of two or more anti-TB drugs and without further anti-TB treatment in the next 60 days. Because it is difficult to correctly determine the outcome of anti-TB treatment other than complete treatment, the number of TB cases with complete anti-TB treatment within 1 year identified in the NHIRD was verified with that reported from the Taiwan Centers for Disease Control (Taiwan CDC).

Definition of DM

Patients were considered as having DM if they had at least one hospital admission or three (or more) outpatient visits with a DM diagnostic code (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 250 and A-code A181) within 1 year.15 To avoid including women with gestational diabetes who returned to normoglycemia after child delivery, diabetes visit claims within 270 days before parturition were excluded.16 Chronic DM complications were identified by at least three ambulatory or inpatient visits with a compatible ICD-9-CM code (diabetic nephropathy 250.4; diabetic retinopathy 250.5; diabetic vasculopathy 250.6; diabetic neuropathy 250.7; and other diabetic complications 250.8 and 250.9).

Comorbidity and Income Status

Underlying comorbidities and low income were noted if they were present before the diagnosis of pulmonary TB according to previous publications (e-Appendix 1).13,17 AIDS was defined by at least two outpatient visits within a period of 180 days, or one inpatient record, or prescription of antiretroviral agents with compatible diagnoses (ICD-9-CM code 042-44 or V08).

Statistical Analysis

Correlation between case numbers in the NHIRD and Taiwan CDC were calculated by using Pearson correlation. Because of limited follow-up period, case numbers in 2010 were not considered in correlation analysis. Intergroup difference was calculated using independent-sample t test for continuous variables and the χ-square test or Fisher exact test for categorical variables, as appropriate.

Cox proportional hazards regression analysis was performed to evaluate the impact of age, sex, year of TB diagnosis, frequency of glycated hemoglobin (HbA1c) check-ups, presence of any diabetic complications and comorbidities, income status, culture positivity after 2 months of treatment, duration of anti-TB treatment (9 months vs 6 months), anti-TB treatment being > 80% consistent with standard regimen, and numbers of days covered by one or fewer anti-TB drugs in the initial 60 days and 180 days of anti-TB treatment on the risk of TB recurrence. Adjusted time-to-event curves were plotted based on regression estimates in the Cox model and average covariate values (average covariate method). Only variables with a two-sided P < .05 were kept in the final model. All analyses were performed using the SAS, version 9.2 (SAS Institute Inc).

Sensitivity Analysis

Sensitivity analyses were performed in three different subpopulations (Fig 1), including (1) cases diagnosed in the DOTs era (2006-2010) (sensitivity analysis 1); (2) receiving isoniazid, rifamycin, ethambutol, and pyrazinamide for > 54 days in the first 2 months and isoniazid and rifamycin for > 162 days in the first 6 months of anti-TB treatment (sensitivity analysis 2); and (3) cases receiving > 90 days of anti-DM medication within 365 calendar days (sensitivity analysis 3).16

A total of 151,571 cases of pulmonary but not extrapulmonary TB were identified in the NHIRD between 1996 and 2010 (Fig 1). Among them, 94,777 cases were diagnosed between 2002 and 2010. The number of pulmonary TB cases with complete anti-TB treatment within 1 year identified in the NHIRD has a good correlation with the number of all TB (Pearson correlation, 0.776) and pulmonary TB cases with complete treatment within 1 year (Pearson correlation, 0.981) reported by the Taiwan CDC (Fig 2).

Figure Jump LinkFigure 2 –  Numbers of TB and PTB cases reported by the TCDC and in the NHIRD as well as number of DM-pulmonary patients with TB selected from NHIRD for further analysis in this study. DM = diabetes mellitus; NHIRD = National Health Insurance Research Database; PTB = pulmonary TB; TCDC = Taiwan Centers for Disease Control.Grahic Jump Location

Between 2002 and 2010, 55,883 patients with pulmonary TB received anti-TB treatment between 6 and 9 months, during which the duration of any non-first-line anti-TB drugs was ≤ 14 days (Fig 1). Among them, 12,688 (22.7%) had concomitant DM, and the other 43,195 did not. The 2-year TB recurrence rates in the DM and non-DM groups were 2.20% (95% CI, 1.94%-2.45%) (279 recurrence cases) and 1.38% (95% CI, 0.89%-1.25%) (597 recurrence cases), respectively (P < .001 by test), both showing a trend of decreasing (Fig 3). The recurrence rate was significantly higher in the DM group in 2002 to 2006 and in 2009 than that in the group without DM.

Figure Jump LinkFigure 3 –  The 2-y TB recurrence rate and its 95% CI in patients with and without DM receiving anti-TB treatment of pulmonary TB between 6 and 9 mo during which the duration of non-first-line anti-TB drugs was ≤ 14 d in the National Health Insurance Research Database of Taiwan. *Represents significant difference (P < .05) between the two groups by χ2 test. See Figure 2 legend for expansion of abbreviation.Grahic Jump Location

Among the 12,688 patients with DM, 5,459 (43.0%) were diagnosed before the implementation of DOTs and 7,229 (57.0%) after. Anti-TB treatment was > 80% consistent with standard regimen in 2,089 (38.3%) of the former and 3,224 (44.6%) of the latter, respectively (P < 0.001 by χ2 test). The 2-year recurrence rate decreased from 3.54% (95% CI, 3.21%-3.86%) (193 recurrences) in pre-DOTs era to 1.19% (95% CI, 1.00%-1.38%) (86 recurrences) in the DOTs era (P < 0.001).

The clinical characteristics of the 12,688 cases are summarized in Table 1. The mean age was 65.8 ± 13.5 years, and 72.6% were men. The most common underlying comorbidity was malignancy (6.5%), followed by COPD (6.2%) and end-stage renal disease requiring long-term dialysis (2.1%). Among them, 4,506 patients (35.5%) were classified into the 9-month anti-TB treatment group (257.4 ± 15.7 days) and 8,182 (64.5%) into the 6-month group (194.3 ± 13.1 days). The distribution of the treatment duration is shown in e-Figure 1. Comparing with the 6-month group, patients in the 9-month group were younger and had a higher prevalence of any diabetic complication, a higher proportion of culture positivity after 2 months of anti-TB treatment, and a lower prevalence of malignancy and COPD. Patients in the 9-month group were more likely to receive HbA1c check-up in the first 2 months and check-ups more than once in the first 6 months. Although the mean differences were < 2 days, numbers of days covered by one or fewer anti-TB drugs in the initial 60 days and 180 days of anti-TB treatment were significantly higher in the 9-month group. The anti-TB treatment was less likely to be consistent with standard regimen in the 9-month group. The 2-year recurrence rate was 2.06% (95% CI, 1.82%-2.31%) and 2.23% (95% CI, 2.01%-2.53%) in the 9-month and 6-month treatment groups, respectively (P = .442).

Table Graphic Jump Location
TABLE 1 ]  Clinical Characteristics at the Diagnosis of Pulmonary TB and Treatment Course of the 12,688 Patients With Diabetes According to the Duration of Anti-TB Treatment

Data presented as No. (%) or mean ± SD. ATT = anti-TB treatment; DOTs = directly observed therapy, short course; HbA1c = glycated hemoglobin.

a 

Cases receiving isoniazid, rifamycin, ethambutol, and pyrazinamide for > 48 d in the first 2 months and isoniazid and rifamycin for > 144 d in the first 6 months of anti-TB treatment.

Of the 12,688 patients with DM, multivariate Cox regression analysis revealed that age (adjusted hazard ratio [HR], 0.97 [95% CI, 0.96-0.98] for per-year increment), later TB diagnosis year (adjusted HR, 0.81 [95% CI, 0.77-0.86] for per-year increment), anti-TB treatment being > 80% consistent with standard regimen (adjusted HR, 0.72 [95% CI, 0.56-0.93]), and 9-month anti-TB treatment (adjusted HR, 0.76 [95% CI, 0.59-0.97]) were associated with lower risk for TB recurrence, whereas male sex (adjusted HR, 1.40 [95% CI, 1.05-1.87]), malignancy (adjusted HR, 1.64 [95% CI, 1.03-2.63]), and culture positivity after 2-month anti-TB treatment (adjusted HR, 1.96 [95% CI, 1.36-2.83]) were associated with higher risk (Table 2). The adjusted time-to-recurrence curves of patients receiving 9-month and 6-month anti-TB treatment were shown in Figure 4A.

Table Graphic Jump Location
TABLE 2 ]  Independent Risk Factors for TB Recurrence Within 2 y After Completion of Anti-TB Treatment Among the 12,688 Patients With Diabetes, by Cox Proportional Hazards Regression Analysis

HR = hazard ratio.

Figure Jump LinkFigure 4 –  A-C, Adjusted time-to-recurrence curves for different anti-TB treatment duration were plotted based on regression estimates in the Cox model and average covariate values (average covariate method) in all of the 12,688 patients with diabetes (A), the 3,184 patients with diabetes with 90% consistent with standard anti-TB treatment (B), and the 10,253 patients with diabetes receiving > 90 days of antidiabetic medication within 365 calendar days (C). HR = hazard ratio.Grahic Jump Location

Among the 7,229 patients with DM with TB diagnosed in the DOTs era (sensitivity analysis 1), 2,383 (33.0%) were classified into the 9-month group. The 2-year recurrence rate was 1.01% (95% CI, 0.83%-1.18%) (24 recurrences) and 1.28% (95% CI, 1.08%-1.47%) (62 recurrences) in the 9-month and 6-month groups, respectively. Duration of anti-TB treatment was not an independent predictor of 2-year TB recurrence (Table 3, e-Table 1). Among the 3,184 and 10,253 cases that had a higher prescription consistencies with standard anti-TB treatment (sensitivity analysis 2) and DM medication (sensitivity analysis 3) (Fig 1), the 2-year TB recurrence rate was 2.14% (95% CI, 1.88%-2.39%) and 2.34% (95% CI, 2.08%-2.60%), respectively. Nine-month anti-TB treatment was a significant predictor in both sensitivity analyses (e-Table 1, Fig 4, Table 3). In all sensitivity analyses, age was an independent factor associated with 2-year TB recurrence (e-Table 1).

Table Graphic Jump Location
TABLE 3 ]  The Impact of Duration of Anti-TB Treatment (9 mo vs 6 mo) on 2-y TB Recurrence in Sensitivity Analyses

DM = diabetes mellitus. See Table 1 and 2 legends for expansion of other abbreviations.

a 

Cases who received isoniazid, rifamycin, ethambutol, and pyrazinamide for > 54 d in the first 2 mo and isoniazid and rifamycin for > 162 d in the first 6 mo of anti-TB treatment.

Using the NHIRD of Taiwan, a powerful tool to investigate the influence and long-term interactions between diseases and treatments, the study has three main findings. First, there is a consistent reduction in 2-year recurrence rate of TB in Taiwan from 2002 to 2010. Second, compatible with previous reports,11,18 the 2-year TB recurrence rate was higher in a diabetic population than that in a nondiabetic population, especially in the pre-DOTs era. Third, although 9-month anti-TB treatment is associated with a lower 2-year TB recurrence rate than 6-month treatment in patients with DM, the protective effect diminishes after implementation of DOTs.

Nonadherence to anti-TB treatment due to either patient or health system factors, as shown by the results of our multivariate analysis, is the chief cause of recurrence and acquired drug resistance in TB.4 By treatment supervision, most patient factors leading to nonadherence can be eliminated, resulting in reduction in TB recurrence.4 Under Taiwan’s National TB Program, DOTs program with TB care worker engagement countrywide has been provided to every smear-positive case since 2006. In 2007, the DOTs program was expanded to cover culture-positive cases and special risk groups, including aboriginal populations, uncooperative patients, and the homeless.19 After implementation of DOTs in Taiwan, the proportion of patients with DM whose anti-TB treatment was > 80% consistent with standard regimen significantly increased from 38.3% to 44.6%, and the 2-year TB recurrence rate in patients with DM significantly decreased from 3.54% to 1.19%. Along with the consistent reduction in TB recurrence in non-DM population, these findings support the continuous government commitment in TB control and the necessity of continuing to implement DOTs in Taiwan.

Prolonging anti-TB treatment is common when response is suboptimal but was not recommended as a routine practice for patients with DM by any treatment guidelines,5,20 including guidelines in Taiwan.14 Anti-TB treatment is recommended to be extended for another 3 months (for a total duration of 9 months) among patients with cavitary TB on initial chest radiography or in those with positive cultures after 2 months of treatment.20 Although a 9-month anti-TB treatment is associated with a lower 2-year recurrence rate in patients with DM, the protective effect waned in the post-DOTs subpopulation. According to the results of our analyses, one needs to treat approximately 370 patients (1/[1.28% − 1.01%]) for an extra 3 months to save one recurrence in the DOTs era. Because the retrieval of information on adverse events in the NHIRD is difficult and unreliable, this study cannot judge the benefit of reducing recurrence by the increased risk of adverse events and cost-effectiveness. Until further evidence supporting an extra 3 months in patients with DM becomes available, implementation of DOTs is still the most effective TB control policy to prevent TB recurrence.

The results of this study confirm the findings in previous reports that DM is consistently associated with an unfavorable outcome.11,18,21 In patients with DM, TB can worsen diabetic control through infection-related glucose intolerance or hyperglycemia caused by interactions between oral hypoglycemic drugs and anti-TB drugs, especially rifampicin.22,23 Similarly, DM may alter the pharmacokinetics of anti-TB drugs by affecting the oral absorption and decreasing the protein binding of drugs and by renal insufficiency or fatty liver with impaired drug clearance.24 Together with a compromised host immunity, suboptimal therapeutic concentration of anti-TB drugs may lead to unfavorable outcomes, including recurrence.

The findings that male sex and concomitant malignancy were associated with a higher TB recurrence rate were consistent with the risk factors of developing active TB in patients with DM in Taiwan.16 However, the finding that the risk of recurrence decreases with age is interesting. In a previous study using molecular genotyping to simultaneously detect the Beijing and non-Beijing strains of Mycobacterium tuberculosis, age was a significant predictor of multiple infections.25 It is speculated that young people have higher risk of TB exposure due to their lifestyle and social activity. It is also possible that young patients with TB acquire their TB because of a genetic and immune predisposition, because the incidence of TB is usually low in young populations.

The present study is limited by the unavailability of mycobacterial study results and radiologic findings. It is possible that anti-TB treatment was extended to 9 months simply because of poor health condition and therapeutic response, such as diabetic complication and persistent smear positivity (confounding by indication). The presence of diabetic complication implies poorly controlled diabetes, which impaired host immunity to TB.79 In addition, persistent smear positivity for acid-fast bacilli is an important predictor of relapse.26 If this is the case, the 2-year recurrence rate of patients receiving longer anti-TB treatment should be higher than those receiving shorter treatment, thus biasing the results toward the null. This implies that the true effect of 9-month anti-TB treatment on the 2-year recurrence rate is likely to be larger than current estimation. Furthermore, without data on genotyping, this study cannot discriminate relapse due to reactivation (the primary concern for extending the duration of anti-TB treatment) from relapse due to exogenous reinfection.27 The reduction in TB recurrence rate may partially be explained by the decrease of TB incidence in Taiwan during the study period.19 This again biased the result to the null and caused underestimation of protection from the 9-month anti-TB treatment. Third, the old age and high prevalence of comorbidities other than DM in the study patients limits the external generalizability of the study results.

There is a consistent decline in 2-year TB recurrence rate from 2002 to 2010 in Taiwan. The recurrence rate in patients with DM is higher than that in patients without DM and can be reduced by treatment supervision. Extending the anti-TB treatment by 3 months in patients with DM may also decrease recurrence rate when treatment is not supervised.

Author contributions: J.-Y. W. is guarantor of the paper. J.-Y. W. contributed to the drafting of the manuscript; J.-Y. W. and C.-H. L. contributed to the approval of the manuscript; M.-C. L., C.-C. S., and K.-M. C. contributed to the review of the manuscript; C.-H. L., L.-N. L., and F.-Y. C. contributed to the revision of the manuscript; C.-C. S. and K.-M. C. contributed to data processing; J.-Y. W., C.-H. L., and L.-N. L. contributed to performing statistical analysis; J.-Y. W., M.-C. L., and C.-H. L. designed the study; and F.-Y. C. contributed as the director responsible for general organization and instruction.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Other contributions: We thank the National Health Research Institute of Taiwan for providing the National Health Insurance Research Database, and Dr Chen-Yuan Chiang for his critique to improve the quality of the paper. Details of the computer code for statistical analyses are available from the corresponding author at chlee.tw@gmail.com.

Additional information: The e-Appendix, e-Figure, and e-Table can be found in the Supplemental Materials section of the online article.

CDC

Centers for Disease Control

DM

diabetes mellitus

DOTs

directly observed therapy, short course

DST

drug susceptibility test

HbA1c

glycated hemoglobin

HR

hazard ratio

ICD-9-CM

International Classification of Diseases, 9th Revision, Clinical Modification

NHIRD

National Health Insurance Research Database

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Figures

Figure Jump LinkFigure 1 –  Flowchart of case selection from the National Health Insurance Research Database of Taiwan. DOTs = directly observed therapy, short course. HREZ = isoniazid, rifamycin, ethambutol, and pyrazinamide.Grahic Jump Location
Figure Jump LinkFigure 2 –  Numbers of TB and PTB cases reported by the TCDC and in the NHIRD as well as number of DM-pulmonary patients with TB selected from NHIRD for further analysis in this study. DM = diabetes mellitus; NHIRD = National Health Insurance Research Database; PTB = pulmonary TB; TCDC = Taiwan Centers for Disease Control.Grahic Jump Location
Figure Jump LinkFigure 3 –  The 2-y TB recurrence rate and its 95% CI in patients with and without DM receiving anti-TB treatment of pulmonary TB between 6 and 9 mo during which the duration of non-first-line anti-TB drugs was ≤ 14 d in the National Health Insurance Research Database of Taiwan. *Represents significant difference (P < .05) between the two groups by χ2 test. See Figure 2 legend for expansion of abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4 –  A-C, Adjusted time-to-recurrence curves for different anti-TB treatment duration were plotted based on regression estimates in the Cox model and average covariate values (average covariate method) in all of the 12,688 patients with diabetes (A), the 3,184 patients with diabetes with 90% consistent with standard anti-TB treatment (B), and the 10,253 patients with diabetes receiving > 90 days of antidiabetic medication within 365 calendar days (C). HR = hazard ratio.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Clinical Characteristics at the Diagnosis of Pulmonary TB and Treatment Course of the 12,688 Patients With Diabetes According to the Duration of Anti-TB Treatment

Data presented as No. (%) or mean ± SD. ATT = anti-TB treatment; DOTs = directly observed therapy, short course; HbA1c = glycated hemoglobin.

a 

Cases receiving isoniazid, rifamycin, ethambutol, and pyrazinamide for > 48 d in the first 2 months and isoniazid and rifamycin for > 144 d in the first 6 months of anti-TB treatment.

Table Graphic Jump Location
TABLE 2 ]  Independent Risk Factors for TB Recurrence Within 2 y After Completion of Anti-TB Treatment Among the 12,688 Patients With Diabetes, by Cox Proportional Hazards Regression Analysis

HR = hazard ratio.

Table Graphic Jump Location
TABLE 3 ]  The Impact of Duration of Anti-TB Treatment (9 mo vs 6 mo) on 2-y TB Recurrence in Sensitivity Analyses

DM = diabetes mellitus. See Table 1 and 2 legends for expansion of other abbreviations.

a 

Cases who received isoniazid, rifamycin, ethambutol, and pyrazinamide for > 54 d in the first 2 mo and isoniazid and rifamycin for > 162 d in the first 6 mo of anti-TB treatment.

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