Sheng-Wei Pan

Statin Use Is Associated With a Lower Risk of TB

BACKGROUND: Statins are widely used to lower cholesterol levels and cardiovascular risk. Further, studies have shown that statins may decrease the risks of infectious diseases and infection‐related mortality; however, the association between statin use and active TB disease remains unclear. METHODS: Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population‐based study. Patients taking statins between 2000 and 2013, without antecedent TB disease, were included. Data from 102,424 statin users and 202,718 age‐, sex‐, and enrollment date–matched subjects were analyzed. The two cohorts were monitored until December 31, 2013, for incident TB disease. The definition of TB disease was validated using the claims database of Taipei Veterans General Hospital. RESULTS: The statin and matched cohorts were observed for 571,568 and 1,027,385 person‐years, respectively. Of the total 305,142 subjects, 1,264 (0.41%) developed subsequent TB disease. Validation study confirmed the accuracy of the definition of TB disease (sensitivity, 96.3%), with excellent interobserver agreement (&kgr; = 1.00). Multivariate analysis revealed a reduced risk of TB disease among the statin cohort (hazard ratio [HR], 0.53; 95% CI, 0.47‐0.61; P < .001). Compared with the matched group, statin use showed a dose‐response relationship with the incident TB disease risk (<180 cumulative defined daily doses [cDDDs]: HR, 1.06; 95% CI, 0.91‐1.24; P = .477; 180 to 365 cDDDs: HR, 0.57; 95% CI, 0.45‐0.72; P < .001; >365 cDDDs: HR, 0.27; 95% CI, 0.22‐0.33; P < .001). CONCLUSIONS: Statin use associates with a lower risk of incident TB disease.

Associations of Metabolic Syndrome and its Components With Mortality in the Elderly: A Cohort Study of 73,547 Taiwanese Adults.

Abstract Available evidence shows that metabolic syndrome (Mets) has clear adverse effects for middle-aged and pre-elderly adults; however, the effect of Mets on mortality among elderly adults remains unclear. In addition, the comparative utility of Mets and its component for predicting mortality among the elderly has not been clearly established. Using data from a large Taiwanese cohort, we evaluated the effect of Mets and its components on subsequent all-cause and cause-specific mortality overtime among the elderly. A total of 73,547 elders (age ≥65 years) participated in the Taipei Elderly Health Examination Program from 2007 to 2010. Mets was diagnosed using the adult treatment panel III criteria, and mortality was ascertained by using national death records. Time-dependent analysis was used to evaluate associations of Mets and its components with all-cause mortality, cardiovascular disease (CVD) mortality, and expanded CVD mortality. This retrospective cohort study found that 42.6% of elders had Mets. During 194,057 person-years of follow-up, 2944 deaths were observed. After adjusting for sociodemographic characteristics and comorbidities, Mets was associated with increased risk of expanded CVD mortality (hazard ratio [HR], 1.27; 95% CI, 1.10–1.46) but not all-cause or CVD mortality. Among Mets components, decreased high-density lipoprotein cholesterol (HDL-C, HR 1.25, 95% CI 1.13–1.37) and hyperglycemia (HR 1.21, 95% CI 1.12–1.31) were associated with a significant increase in all-cause mortality. Hypertension and low HDL-C were predictors of CVD mortality and expanded CVD mortality, and, as compared with Mets, were associated with a higher risk of expanded CVD mortality. The present findings indicate that, in elderly adults, individual components of Mets are better predictors of all-cause and cause-specific mortality than is Mets as a whole. Our results suggest that future efforts should focus on preventing and managing individual risk factors (particularly hypertension, low HDL-C, and hyperglycemia) rather than on “diagnosing” Mets in elders.

Latent Tuberculosis Infection and the Risk of Subsequent Cancer.

AbstractThe association of latent tuberculosis infection (LTBI) with subsequent cancer remains unclear. We investigated the risk of future cancer among tuberculosis (TB) contacts with or without subsequent TB activation. Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. TB contacts during 1997 to 2012 were included as the study cohort. Patients with antecedent cancer and TB were excluded. Data from 11,522 TB contacts and 46,088 age-, sex-, and enrollment date–matched subjects during 1997 to 2012 were analyzed. The 2 cohorts were monitored until December 31, 2012 for incidence of cancer and TB infection. LTBI was defined as a TB contact with subsequent TB activation. The primary endpoint was occurrence of newly diagnosed cancer. There was no difference in cancer development between the TB contact cohort and comparison cohort (log-rank test, P = 0.714). After multivariate adjustment, the hazard ratio (HR) for cancer among the LTBI patients was 2.29 [95% confidence interval (CI), 1.26–4.17; P = 0.007]. There was increase in cancer incidences for several specific cancer types, including multiple myeloma (HR 340.28), lung (HR 2.69), kidney and bladder (HR 6.16), hepatobiliary (HR 2.36), and gastrointestinal (HR 2.99) cancers. None of the 136 TB contacts who received isoniazid prophylaxis developed cancer. LTBI patients had a higher risk of future cancer.

The Risk of TB in Patients With Type 2 Diabetes Initiating Metformin vs Sulfonylurea Treatment

Background: Metformin and the sulfonylureas are common initial antidiabetic agents; the former has demonstrated anti‐TB action in in vitro and animal studies. The comparative effect of metformin vs the sulfonylureas on TB risk in patients with type 2 diabetes mellitus (T2DM) remains unclear. Methods: In this retrospective cohort study, patients without chronic kidney disease who received a T2DM diagnosis during 2003 to 2013 were identified from the Taiwan National Health Insurance Research Database. Participants with ≥ 2 years of follow‐up were reviewed and observed for TB until December 2013. Patients receiving metformin ≥ 60 cumulative defined daily dose (cDDD) and sulfonylureas < 15 cDDD in the initial 2 years were defined as metformin majors; it was the inverse for sulfonylurea majors. The two groups were matched 1:1 by propensity score and compared for TB risk by multivariate Cox regression analysis. Results: Among 40,179 patients with T2DM, 263 acquired TB (0.65%) over a mean follow‐up of 6.1 years. In multivariate analysis, the initial 2‐year dosage of metformin, but not that of the sulfonylureas, was an independent predictor of TB (60‐cDDD increase (adjusted hazard ratio [HR], 0.931; 95% CI, 0.877–0.990) after adjustment by cofactors, including adapted diabetes complication severity index. Metformin majors had a significantly lower TB risk than that of sulfonylurea majors before and after matching (HR, 0.477; 95% CI, 0.268–0.850 and HR, 0.337; 95% CI, 0.169–0.673; matched pairs, n = 3,161). Compared with the reference group (initial 2‐year metformin < 60 cDDD), metformin treatment showed a dose‐dependent association with TB risk (60–219 cDDD; HR, 0.860; 95% CI, 0.637–1.161; 220–479 cDDD, HR, 0.706; 95% CI, 0.485–1.028; ≥ 480 cDDD, HR, 0.319; 95% CI, 0.118–0.863). Conclusions: Metformin use in the initial 2 years was associated with a decreased risk of TB, and metformin users had a reduced risk compared with their sulfonylurea comparators.

The Risk of Depressive Disorder Among Contacts of Tuberculosis Patients in a TB-endemic Area: A Population-based Cohort Study.

AbstractTuberculosis (TB) disease may be transmitted to close contacts of index cases, causing physical illness. No studies have investigated the risk of developing depressive disorder among TB contacts in a TB-endemic area.Adult participants with a new diagnosis of TB contact (ICD-9-CM codes V01.1 plus chest radiographic order) since January 1, 2008, were identified from the National Health Insurance Research Database in Taiwan. A control cohort matched for age (±5 y), sex, enrolled years, and income level was selected. These 2 cohorts were followed until December 31, 2012, and observed for the development of depressive disorder. The Kaplan-Meier method and the log-rank test were used to examine the difference in cumulative incidences of depressive disorder between groups. Cox proportional-hazard models were used to calculate adjusted hazard ratios (aHRs) for depressive disorder.The TB contact cohort consisted of 9046 patients and matched controls of 36,184 ones. The mean age of TB contacts was 44.7 years, and 56.0% of them were women. During a mean follow-up period of 2.5 years, 127 (1.40%) TB contacts and 521 (1.44%) matched controls developed depressive disorder. TB exposure was found to be an independent risk factor of depressive disorder in women (aHR 1.34, 95% confidence interval [CI] 1.07–1.68), but not in men (aHR 0.71, 95% CI 0.48–1.06) after adjusting for age, comorbidities, and income levels. The risk of depression was significantly higher for female TB contacts than for matched controls in the first and second years (aHR 1.49, 95% CI 1.03–2.14; and aHR 1.53, 95% CI 1.05–2.23, respectively), but not thereafter. Of note, 67 (0.74%) TB contacts and 88 (0.24%) matched controls developed active TB, but none of them had subsequent depressive disorder during follow-up periods.Female TB contacts had an increased risk of depression within the first 2 years after exposure. Clinicians should consider conducting depression evaluations in addition to routine TB contact investigations in this subgroup population.

Microbiological Persistence in Patients With Mycobacterium avium Complex Lung Disease: The Predictors and the Impact on Radiographic Progression

Background Persistent growth of Mycobacterium avium complex (MAC) in the lungs indicates continuous infection in MAC lung disease (MAC-LD), but its clinical significance has not been investigated. We aimed to evaluate the predictors of persistent culture-positivity for MAC (MAC-PP) and its impact on radiographic deterioration in MAC-LD. Methods Patients with MAC-LD at multiple medical centers from 2011 to 2016 were enrolled retrospectively. Microbiological persistence of MAC-LD was defined as MAC-PP exceeding 1 year, in contrast with the negative-conversion group. The outcome was radiographic progression, namely, increased number of involved lung areas or cavitary formation. Results Among 126 patients with MAC-LD, 75 (60%) were in the MAC-PP group; these patients had a higher proportion of radiographic progression (54%) than patients in the negative-conversion group (odds ratio [OR], 3.318; 95% confidence interval, 1.146-9.612). Independent predictors of MAC-PP were low body mass index (BMI), radiographic nodular-bronchiectatic (NB) pattern, and increase in the highest grade of acid-fast bacilli smear (AFS). Patients with BMI <21 kg/m2, NB pattern, and positive AFS had an OR of 17.7 for MAC-PP, and those with ≥2 of the factors had a 4.5-fold increased OR for MAC-PP relative to the comparison group. Other than MAC-PP, the highest AFS grade and no anti-MAC treatment were correlated with radiographic progression. Conclusion Microbiological persistence in patients with MAC-LD is not uncommon and leads to an increased risk of radiographic progression. The predictors of MAC-PP are low BMI, NB pattern, and high AFS grade; if these risk factors are present, anti-MAC treatment should be seriously considered.

Role of TREM-1 in pulmonary tuberculosis patients- analysis of serum soluble TREM-1 levels

Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured. We correlated serum biomarkers and clinical presentations and treatment outcomes of PTB cases. We also utilized immunohistochemistry (IHC) to visualize TREM-1-expressing cells in lung tissues from PTB patients. A total of 86 PTB, 41 LTBI, and 20 non-TB, non-LTBI subjects were enrolled. Serum levels of sTREM-1 and CRP significantly increased in PTB patients; these higher serum levels were correlated with more advanced involvement in chest films and higher bacteria burden in sputum. In multivariate analysis, serum levels of sTREM-1 >260 pg/mL and CRP >2.6 mg/L were independent predictors for on-treatment mortality. Abundant TREM-1-expressing macrophages were identified in lung tissues from PTB samples. In conclusion, serum levels of sTREM-1 correlated with disease severity and treatment outcomes in PTB patients.

Influenza Vaccination and Incident Tuberculosis among Elderly Persons, Taiwan1

Experimental studies have demonstrated that influenza vaccination may protect against tuberculosis (TB) through a Th17 response. This nationwide cohort study aimed to evaluate the association of influenza vaccination with incident TB among elderly persons in Taiwan. This 2005–2012 study included 99,982 elderly persons (64,290 vaccinated and 35,692 unvaccinated) from the Taiwan National Health Insurance Research Database. During the 738,367 person-years of follow-up, 1,141 (1.14%) persons had incident TB. The cumulative incidences of TB were 145.2 cases/100,000 person-years among vaccinated elderly persons and 175.5 cases/100,000 person-years among unvaccinated elderly persons (p = 0.002). The time-dependent Cox proportional hazards model revealed that influenza vaccination was an independent protective factor for incident TB. Our results suggest that influenza vaccination is associated with a lower risk of incident TB among elderly persons in Taiwan. Further investigation of biologic mechanisms is warranted.